Novel small-molecule agents in overcoming tumor regression in cancers

Abstract

The present invention discloses a Novel Small-Molecule Agents in overcoming tumor regression in Cancers The novel anti-cancer molecules comprises of structures in accordance with Formula (1). Formula (1) or any derivative thereof, pharmaceutically acceptable salt thereof, or combination thereof in which: X1, X2, X3, X4 are is imino group or secondary amine group or methylene group or Methylidene group or oxo group or Oxygen atom Y1, Y2 is alkyl group or amino group or hydroxyl group Z is secondary amine group or methylene group

Description

[0001] TITLE: NOVEL SMALL-MOLECULE AGENTS IN OVERCOMING TUMOR REGRESSION IN CANCERS

[0002] FIELD OF THE INVENTION:

[0003] The present invention relates to Novel Small-Molecule Agents in overcoming tumor regression in Cancers. The invention also relates to the pharmaceutical formulation for the treatment of cancer.

[0004] BACKGROUND OF THE INVENTION:

[0005] Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body. Cancer can start almost anywhere in the human body, which is made up of trillions of cells. Normally, human cells grow and multiply (through a process called cell division) to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place. Sometimes this orderly process breaks down, and abnormal or damaged cells grow and multiply when they shouldn’t. These cells may form tumors, which are lumps of tissue. Tumors can be cancerous or not cancerous (benign).

[0006] Cancer is a genetic disease — that is, it is caused by changes to genes that control the way our cells function, especially how they grow and divide. The body normally eliminates cells with damaged DNA before they turn cancerous. But the body’s ability to do so goes down as we age. This is part of the reason why there is a higher risk of cancer later in life.

[0007] There are many types of cancer treatment. The types of treatment that you receive will depend on the type of cancer you have and how advanced it is. Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Hormone therapy is a treatment that slows or stops the growth of breast and prostate cancers that use hormones to grow. Hyperthermia is a type of treatment in which body tissue is heated to as high as 113 °F to help damage and kill cancer cells with little or no harm to normal tissue. Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. Photodynamic therapy uses a drug activated by light to kill cancer and other abnormal cells. Radiation therapy is a type of cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Stem cell transplants are procedures that restore stem cells that grow into blood cells in people who have had theirs destroyed by high doses of chemotherapy or radiation therapy. When used to treat cancer, surgery is a procedure in which a surgeon removes cancer from your body. Targeted therapy is a type of cancer treatment that targets the changes in cancer cells that help them grow, divide, and spread. Most targeted therapies are either smallmolecule drugs or monoclonal antibodies.

[0008] Small-molecule drugs are small enough to enter cells easily, so they are used for targets that are inside cells. Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. The Small molecules in targeted cancer therapy includes kinase inhibitors, receptor tyrosine kinase inhibitors, non-receptor tyrosine kinase inhibitors, serine / theonine kinase inhibitors, epigenetic inhibitors, BCL-2 inhibitors, HEDGEHOG pathway inhibitors, proteasome inhibitors and PARP inhibitors. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate undesirable side effects and drug resistance. Thus their exists a need in the state of art to develop a novel small molecules which exhibits high response rate, minimal / no side effects with nil drug resistance.

[0009] OBJECT OF THE INVENTION:

[0010] The main object of the present invention is to develop Novel Small-Molecule Agents in overcoming tumor regression in Cancers.

[0011] Another object of the present invention is to develop Novel Small-Molecule Agents in overcoming tumor regression in Cancers which exhibits high response rate, minimal / no side effects with nil drug resistance.

[0012] Yet another object of the present invention is to formulate anti -cancer pharmaceutical formulation employing developed novel molecules.

[0013] Further object of the present invention is to utilize the novel anti-cancer molecules and anti-cancer pharmaceutical formulation for the subjects suffering from cancer.

[0014] BRIEF DESCRIPTION OF DRAWINGS:

[0015] The foregoing and following information as well as other features of this disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings. Figure 1 depicts the spectrum of compound A a. Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0016] Figure 2 depicts the spectrum of compound B a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0017] Figure 3 depicts the spectrum of compound C a. Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0018] Figure 4 depicts the spectrum of compound D a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0019] Figure 5 depicts the spectrum of compound E a. Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0020] Figure 6 depicts the spectrum of compound F a. Spectrum b.13C NMR Spectrum c. Mass Spectrum Figure 7 depicts the spectrum of compound G a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0021] Figure 8 depicts the spectrum of compound H a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0022] Figure 9 depicts the spectrum of compound I a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0023] Figure 10 depicts the spectrum of compound J a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0024] Figure 11 depicts the spectrum of compound K a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0025] Figure 12 depicts the spectrum of compound L a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0026] Figure 13 depicts the spectrum of compound M a.1H NMR Spectrum b.13C NMR Spectrum c. Mass Spectrum

[0027] Figure 14 depicts the anticancer activity of compound A Figure 15 depicts the anticancer activity of compound B Figure 16 depicts the anticancer activity of compound C Figure 17 depicts the anticancer activity of compound D Figure 18 depicts the anticancer activity of compound E Figure 19 depicts the anticancer activity of compound F Figure 20 depicts the anticancer activity of compound G Figure 21 depicts the anticancer activity of compound H Figure 22 depicts the anticancer activity of compound I Figure 23 depicts the anticancer activity of compound J Figure 24 depicts the anticancer activity of compound K Figure 25 depicts the anticancer activity of compound L Figure 26 depicts the anticancer activity of compound M

[0028] SUMMARY OF THE INVENTION:

[0029] The present invention discloses a Novel Small-Molecule Agents in overcoming tumor regression in Cancers. The novel anti-cancer molecules comprises of structures in accordance with Formula 1.

[0030]

[0031] Formula 1 or any derivative thereof, pharmaceutically acceptable salt thereof, or combination thereof in which:

[0032] Xi, X2, X3, X4 are is imino group or secondary amine group or methylene group or Methylidene group or oxo group or Oxygen atom

[0033] Y 1, Y2 is alkyl group or amino group or hydroxyl group

[0034] Z is secondary amine group or methylene group

[0035] DETAILED DESCRIPTION OF THE INVENTION:

[0036] Definitions

[0037] “Alkyl” or “alkyl group” refers to a fully saturated, straight or branched hydrocarbon chain having from one to fifteen carbon atoms, and which is attached to the rest of the molecule by a single bond. Unless stated otherwise specifically in the specification, an alkyl group can be optionally substituted.

[0038] “Methylene” group refers to -CH2-

[0039] “Methylidene” group refers to =CH2

[0040] “secondary amine group” group refers to -NH-

[0041] “Imino” group refers to =NH “Hydroxyl” refers to -OH

[0042] “Amino” refers to -NH2

[0043] “Oxygen atom refers to -O-

[0044] “Oxo” refers to =0

[0045] - denotes single bond

[0046] = denotes double bond

[0047] “Pharmaceutically acceptable salts” include, when appropriate, pharmaceutically acceptable base addition salts and acid addition salts, As used herein, the term “pharmaceutically acceptable” infers that the salt is not biologically or otherwise undesirable; for example, the material may be added to a pharmaceutical composition and administered to a subject without causing significant undesirable effects.

[0048] The term “therapeutically effective” applied to dose or amount refers to that quantity of a compound or pharmaceutical formulation that is sufficient to result in a desired clinical benefit after administration to a patient in need thereof. It is to be understood that an effective amount may be in one or more doses, e.g., a single dose or multiple doses may be needed to achieve the desired treatment endpoint.

[0049] The terms “treating” or “treatment”, as used herein, refer to a method or procedure for obtaining beneficial or desired results — for example, clinical results. Beneficial or desired results may include: (1) alleviating one or more symptoms caused by or associated with a disease, disorder, or condition; (2) reducing the extent of the disease, disorder, or condition; (3) slowing or stopping the development or progression of one or more symptoms caused by or associated with the disease, disorder, or condition (for example, stabilizing the disease, disorder, or condition); and (4) relieving the disease, for example, by causing the regression of one or more clinical symptoms (e.g., ameliorating the disease state, enhancing the effect of another medication, delaying or stopping the progression of the disease, increasing the quality of life, and / or prolonging survival rates).

[0050] The illustrative embodiments described in the detailed description, are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

[0051] Generally the present invention discloses novel anticancer molecules for treating cancer.

[0052] In one of the preferred embodiment, the present invention shall disclose a Novel Small- Molecule Agents in overcoming tumor regression in Cancers, comprising of structure in accordance with formula 1

[0053] Formula 1 or any derivative thereof, pharmaceutically acceptable salt thereof, or combination thereof in which: Xi, X2, X3, X4 are is imino group or secondary amine group or methylene group or Methylidene group or oxo group or Oxygen atom

[0054] Y 1, Y2 is alkyl group or amino group or hydroxyl group

[0055] Z is secondary amine group or methylene group

[0056] According to the invention, in the molecule of Formula 1

[0057] Xi is imino group

[0058] X2 is Oxo group

[0059] X3 is imino group

[0060] X4 is Oxygen atom

[0061] Y 1 is Methyl group

[0062] Y2 is Methyl group

[0063] Z is secondary amine group

[0064] In accordance with the invention, the molecule of formula 1, having a structure of Compound A is

[0065] Compound A

[0066] According to the invention, in the molecule of Formula 1

[0067] Xi is imino group

[0068] X2 is methylidene group X3 is Oxo group

[0069] X4 is Oxygen atom

[0070] Y 1 is Methyl group

[0071] Y2 is Amino group

[0072] Z is secondary amine group

[0073] In accordance with the invention, the molecule of formula 1, having a structure of Compound B is

[0074] Compound B

[0075] According to the invention, in the molecule of Formula 1

[0076] Xi is methylidene group

[0077] X2 is imino group

[0078] X3 is methylidene group

[0079] X4 is Oxygen atom

[0080] Y 1 is Methyl group

[0081] Y2 is Methyl group

[0082] Z is secondary amine group In accordance with the invention, the molecule of formula 1, having a structure of Compound C is

[0083] Compound C

[0084] According to the invention, in the molecule of Formula 1

[0085] Xi is Oxo group

[0086] X2 is imino group

[0087] X3 is Oxo group

[0088] X4 is Oxygen atom

[0089] Y 1 is hydroxyl group

[0090] Y2 is hydroxyl group

[0091] Z is secondary amine group In accordance with the invention, the molecule of formula 1, having a structure of Compound D is

[0092] Compound D

[0093] According to the invention, in the molecule of Formula 1

[0094] Xi is methylidene group

[0095] X2 is imino group

[0096] X3 is Oxo group

[0097] X4 is secondary amine group

[0098] Y 1 is methyl group

[0099] Y2 is methyl group

[0100] Z is secondary amine group

[0101] In accordance with the invention, the molecule of formula 1, having a structure of Compound E is

[0102] Compound E

[0103] According to the invention, in the molecule of Formula 1

[0104] Xi is methylidene group

[0105] X2 is imino group

[0106] X3 is Oxo group

[0107] X4 is secondary amine group

[0108] Y 1 is hydroxyl group

[0109] Y2 is methyl group

[0110] Z is secondary amine group In accordance with the invention, the molecule of formula 1, having a structure of Compound F is

[0111] Comparand F

[0112] According to the invention, in the molecule of Formula 1

[0113] Xi is methylidene group

[0114] X2 is imino group

[0115] X3 is Oxo group

[0116] X4 is secondary amine group

[0117] Y 1 is methyl group

[0118] Y2 is amino group

[0119] Z is secondary amine group In accordance with the invention, the molecule of formula 1, having a structure of Compound G is

[0120] According to the invention, in the molecule of Formula 1

[0121] Xi is Oxo group

[0122] X2 is methylidene group

[0123] X3 is Oxo group

[0124] X4 is secondary amine group

[0125] Y 1 is hydroxyl group

[0126] Y2 is hydroxyl group

[0127] Z is secondary amine group In accordance with the invention, the molecule of formula 1, having a structure of Compound H is

[0128] CnmpomdH

[0129] According to the invention, in the molecule of Formula 1

[0130] Xi is Oxo group

[0131] X2 is methylidene group

[0132] X3 is Oxo group

[0133] X4 is secondary amine group

[0134] Y 1 is Methyl group

[0135] Y2 is Methyl group

[0136] Z is secondary amine group In accordance with the invention, the molecule of formula 1, having a structure of Compound I is

[0137] According to the invention, in the molecule of Formula 1

[0138] Xi is Oxo group

[0139] X2 is methylidene group

[0140] X3 is Oxo group

[0141] X4 is methylene group

[0142] Y 1 is amino group

[0143] Y2 is amino group

[0144] Z is methylene group In accordance with the invention, the molecule of formula 1, having a structure of Compound J is

[0145] According to the invention, in the molecule of Formula 1

[0146] Xi is Oxo group

[0147] X2 is imino group

[0148] X3 is Oxo group

[0149] X4 is Oxygen atom

[0150] Y 1 is methyl group Y2 is methyl group

[0151] Z is methylene group

[0152] In accordance with the invention, the molecule of formula 1, having a structure of Compound K is

[0153] According to the invention, in the molecule of Formula 1

[0154] Xi is Oxo group

[0155] X2 is imino group

[0156] X3 is Oxo group

[0157] X4 is Oxygen atom

[0158] Y 1 is amino group

[0159] Y2 is amino group

[0160] Z is methylene group

[0161] In accordance with the invention, the molecule of formula 1, having a structure of Compound L is

[0162] According to the invention, in the molecule of Formula 1

[0163] Xi is Oxo group

[0164] X2 is methylidene group

[0165] X3 is methylidene group

[0166] X4 is Oxygen atom

[0167] Y 1 is methyl group

[0168] Y2 is methyl group

[0169] Z is methylene group In accordance with the invention, the molecule of formula 1, having a structure of Compound M is

[0170] The chemical structures for molecule of formula 1 or any of compound A-M can be prepared by routine chemistry.

[0171] The chemical structures for any of molecules of Formulae 1 or compound A-M can be prepared by routine chemistry.

[0172] In one embodiment, example compound A can be prepared by the Scheme I provided below.

[0173] The synthesized compounds A-M were next subject to molecular characterization to ascertain the structure of the compounds.

[0174] Molecules Characterization:

[0175] The purity of synthesized products verified by the melting point, Thin Layer Chromatography, HPLC, IR, Mass Spectroscopy and NMR analysis. From spectral analysis and Figure 1-13, the structure of the synthesized compound A & B is elucidated as follows in Table 1.

[0176] Table 1

[0177]

[0178] In another preferred embodiment the present invention shall a pharmaceutical composition, comprising the molecules of Formulae 1 or any of compound A - M and a pharmaceutically acceptable carrier thereof.

[0179] In some embodiments, the molecules of Formulae 1 or any of compound A - M may encompass both the cis- and trans- isomers. In some embodiments, the molecules of Formulae 1 or any of compound A - M may be a mixture of cis- and trans- isomers. In some embodiments, the molecules of Formulae 1 or any of compound A - M may be cis- isomer. In some embodiments, the molecules of Formulae 1 or any of compound A - M may be trans- isomer.

[0180] In some embodiments, the molecules of Formulae 1 or any of compound A - M may encompass either R or Sstereoisomers and a mixture of stereoisomers. In some embodiments, the molecules of Formulae 1 or any of compound A - M may encompass both racemic isomers and enantiomeric isomers

[0181] The present disclosure also includes pharmaceutical compositions comprising a therapeutically effective amount of one or more compounds disclosed herein. In some embodiments, pharmaceutical compositions comprise a therapeutically effective amount of one or more the molecules of Formulae 1 or any of compound A - M, or pharmaceutically acceptable salts thereof. In other embodiments, pharmaceutical compositions comprise a therapeutically effective amount of the molecules of Formulae 1 or any of compound A - M, or pharmaceutically acceptable salts thereof.

[0182] In another preferred embodiment, the present invention shall disclose an article of manufacture, comprising: (i) an effective amount of any of the molecules of Formulae 1 or any of compound A - M or a stereoisomer or tautomer thereof, or a pharmaceutical composition described above; and (ii) instructions for use in treating cancer.

[0183] In yet another preferred embodiment, the present invention shall disclose a kit, comprising: (i) an effective amount of any of the molecules of Formulae 1 or any of the compound A - M or a stereoisomer or tautomer thereof, or a pharmaceutical composition described above; and (ii) instructions for use in treating cancer. In some embodiments, the present invention discloses a method of treating cancer in a patient in need thereof, comprising administering the molecules of Formulae 1 or any of the compound A - M or a stereoisomer or tautomer thereof, or a pharmaceutical composition described above.

[0184] In some embodiments, the compounds of the present disclosure (the molecules of Formulae 1 or any of the compound A - M) are administered to a patient with cancer. In the context of some embodiments of the present invention, the term "cancer" refers, but not limited to acute lymphoblastic, acute lymphoblastic leukemia, acute lymphocytic leukemia, acute myelogenous leukemia, acute myeloid leukemia, adrenocortical carcinoma, AIDS -related lymphoma, anal cancer, appendix cancer, basal-cell carcinoma, bladder cancer, brain cancer, brainstem glioma, breast cancer, bronchial adenomas / carcinoids, Burkitt's lymphoma, carcinoid tumor, cerebellar or cerebral astrocytoma, cervical cancer, cholangiocarcinoma, chondrosarcoma, chronic lymphocytic or chronic lymphocytic leukemia, chronic myelogenous or chronic myeloid leukemia, chronic myeloproliferative disorders, colon cancer, cutaneous T- cell lymphoma, desmoplastic small round cell tumor, endometrial uterine cancer, ependymoma, esophageal cancer, Ewing's sarcoma, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic bile duct cancer, gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), gestational trophoblastic tumor, glioma of the brain stem, hairy cell leukemia, head and neck cancer, heart cancer, hepatocellular (liver) cancer, Hodgkin lymphoma, hypopharyngeal cancer, hypothalamic and visual pathway glioma, intraocular melanoma, Islet cell carcinoma, Kaposi sarcoma, laryngeal cancer, leukaemia, lip and oral cavity cancer, liposarcoma, lymphoma, male breast cancer, malignant mesothelioma, medulloblastoma, melanoma, Merkel cell skin carcinoma, mesothelioma, metastatic squamous neck cancer, mouth cancer, multiple endocrine neoplasia syndrome, multiple myeloma, multiple myeloma / plasma cell neoplasm, mycosis fungoides, myelodysplastic / myeloproliferative diseases, nasal cavity and paranasal sinus cancer, nasopharyngeal carcinoma, neuroblastoma, non-Hodgkin lymphoma, non-melanoma skin cancer, non- small cell lung cancer, oligodendroglioma, oral cancer, oropharyngeal cancer, osteosarcoma and malignant fibrous histiocytoma, ovarian cancer, ovarian germ cell tumor, ovarian epithelial cancer (surface epithelial- stromal tumor), ovarian low malignant potential tumor, pancreatic cancer, paranasal sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineal astrocytoma, pineal germinoma, pineoblastoma and supratentorial primitive neuroectodermal tumors, pituitary adenoma, plasma cell neoplasia, pleuropulmonary blastoma, primary carcinoma, primary central nervous system lymphoma, primary liver cancer, prostate cancer, rectal cancer, renal cell carcinoma, renal pelvis and ureter carcinoma, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, Sezary syndrome, small cell lung cancer, small intestine cancer, soft tissue sarcoma, squamous cell carcinoma, stomach cancer, supratentorial primitive neuroectodermal tumor, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, transitional cell cancer of the renal pelvis and ureter, urethral cancer, uterine sarcoma, vaginal cancer, visual pathway and hypothalamic glioma, vulvar cancer, Waldenstrom macroglobulinemia, and Wilms tumor, The molecules are also a good candidate for KRAS oncogene mutation in different cancers

[0185] In some embodiments, the cancer is colon, prostate, breast, or leukemia. In some embodiments, the cancer is a stage 4 cancer. In some embodiments, colon, prostate, breast, or leukemia are stage 4. In some embodiment, the cancer is KRAS oncogene mutation in different cancers.

[0186] In certain embodiments, the molecules of Formulae 1 or any of the compound A - M, or compositions described herein are administered in combination with one or more of other antibody molecules, chemotherapy, other anti-cancer therapy (e.g., targeted anticancer therapies, gene therapy, viral therapy, RNA therapy bone marrow transplantation, nanotherapy, or oncolytic drugs), cytotoxic agents, immune-based therapies (e.g., cytokines or cell-based immune therapies), surgical procedures (e.g., lumpectomy or mastectomy) or radiation procedures, or a combination of any of the foregoing.

[0187] Alternatively, or in combination with the aforesaid combinations, the methods and compositions described herein can be administered in combination with one or more of: a vaccine, e.g., a therapeutic cancer vaccine; or other forms of cellular immunotherapy.

[0188] In another embodiment, the combination therapy is used in combination with one, two or all of oxaliplatin, leucovorin or 5-FU (e.g., a FOLFOX co-treatment). Alternatively or in combination, combination further includes a VEGF inhibitor (e.g., a VEGF inhibitor as disclosed herein).

[0189] Non-limiting examples of additional therapeutic agent which can be combined with the methods disclosed herein include :taxol, imatinif, doxorubicin, paclitaxel, fluorouracil (5-FU), and vinblastin.

[0190] The molecules of Formulae 1 or compounds A -M of the present inventions is next subjected to experimental studies to ascertain anti-cancer activity.

[0191] The anti-cancer studies for Compound A (Figure 14) indicates its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a high viability of 89.86% at 1 pM, but this significantly declines to 26.58% at 1000 pM, suggesting a notable dose-dependent cytotoxic effect. HT 29 cells also show a decrease from 71.98% to 5.81% across the same concentration range, reflecting their high sensitivity to the compound. HeLa cells exhibit the lowest initial viability at 52.48%, with a decrease to 14.26% at 1000 pM. The consistent reduction in viability across all three cell lines suggests that Compound A has a potent cytotoxic effect, particularly on HT 29 cells, which appear to be the most affected. These findings highlight Compound A's potential as an anticancer agent, and effectiveness against different cancer types.

[0192] The anti-cancer studies for Compound B (Figure 15) illustrates its impact on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells show a decline in viability from 76.55% at 1 pM to 30.78% at 1000 pM, indicating a significant cytotoxic effect as the concentration increases. HT 29 cells start at 72.13% viability and decrease sharply to 2.83% at the highest concentration, demonstrating a heightened sensitivity to the compound. In contrast, HeLa cells begin with a high viability of 90.54% at 1 pM, but this too diminishes to 27.03% at 1000 pM, although they maintain higher viability compared to the other lines throughout the experiment. Overall, the results suggest that Compound B has a potent cytotoxic effect across all tested cell lines, with HT 29 cells being particularly susceptible. These findings highlight the compound's potential as an anticancer agent, and effectiveness across different cancer types.

[0193] The anti-cancer studies for Compound C (Figure 16) indicates its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a viability of 75.24% at 1 pM, which decreases to 29.64% at 1000 pM, showcasing a pronounced dose-dependent cytotoxic effect. HT 29 cells exhibit a similar trend, beginning at 71.36% and plummeting to 3.87% at the highest concentration, reflecting a marked sensitivity to the compound. HeLa cells maintain the highest initial viability at 89.86%, but this too declines to 26.8% at 1000 pM, indicating that while they are more resilient than the other lines, they still experience significant toxicity. Overall, the results demonstrate that Compound C exerts a substantial cytotoxic effect across all three cancer cell lines, with HT 29 cells being the most affected. These findings suggest the compound’s potential as an anticancer agent and efficacy against various cancer types. The anti-cancer studies for Compound D (Figure 17) highlights its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells show a decrease in viability from 75.88% at 1 pM to just 3.05% at 1000 pM, indicating a strong dosedependent cytotoxic effect. HT 29 cells also demonstrate significant sensitivity, starting at 75.59% and dropping to 22.27% with increasing concentrations. HeLa cells, beginning with a viability of 59.34%, decline to 7.88% at the highest concentration, suggesting they are less affected than the other two lines but still experience considerable toxicity. Overall, the results suggest that Compound D has a potent cytotoxic effect across all three cell lines, with MCF 7 and HT 29 cells being particularly sensitive. These findings underscore the compound’s potential as an anticancer agent.

[0194] The anti-cancer studies for Compound E (Figure 18) reveals its impact on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a viability of 75.11% at 1 pM, which declines significantly to -5.04% at 1000 pM, indicating an unexpected result that suggests complete cytotoxicity or potential methodological issues at high concentrations. HT 29 cells show a decrease from 75.59% to 17.77%, reflecting notable sensitivity to the compound. HeLa cells, beginning at 55.53%, decline to 8.51% at the highest concentration, indicating that they also experience substantial toxicity, though they retain some viability. Overall, the results suggest that Compound E has a strong cytotoxic effect, especially on HT 29 and HeLa cells.

[0195] The anti-cancer studies for Compound F (Figure 19) illustrates its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a viability of 71.3% at 1 pM, but this sharply decreases to 0.46% at 1000 pM, indicating a significant and nearly complete cytotoxic effect at high concentrations. HT 29 cells also demonstrate a marked decline, starting at 74.02% and dropping to 9.18% by 1000 pM, reflecting substantial sensitivity to the compound. HeLa cells, beginning at 58.7%, decrease to 7.88%, indicating that they experience toxicity as well, but they retain slightly higher viability compared to the other lines. Overall, the results suggest that Compound F exerts a potent cytotoxic effect across all three cancer cell lines, with MCF 7 cells being the most affected. These findings highlight Compound F's potential as an anticancer agent.

[0196] The anti-cancer studies for Compound G (Figure 20) demonstrates its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells begin with a viability of 55.54% at 1 pM, which gradually declines to 20.21% at 1000 pM, indicating a steady dose -dependent cytotoxicity. HT 29 cells show a similar trend, starting at 57.19% and decreasing to 20.21% at the highest concentration, reflecting consistent sensitivity to the compound. HeLa cells, beginning at 61.23%, also exhibit a gradual decline in viability, ending at 18.26%. Overall, the results suggest that Compound G has a moderate cytotoxic effect across all three cell lines, with each line displaying a comparable response to increasing concentrations. These findings highlight the compound’s potential as an anti cancer agent, in therapeutic contexts.

[0197] The anti-cancer studies for Compound H (Figure 21) reveals its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a viability of 64.61% at 1 pM, which decreases significantly to 13.02% at 1000 pM, indicating a clear dose-dependent cytotoxic effect. HT 29 cells show a more pronounced decline, beginning at 53.81% and plummeting to 7.41% at the highest concentration, suggesting a high sensitivity to the compound. HeLa cells, starting at 79.08%, also exhibit a significant reduction, ultimately dropping to just 0.65% at 1000 pM, indicating extreme sensitivity. Overall, the results indicate that Compound H exerts a potent cytotoxic effect across all three cell lines, particularly impacting HT 29 and HeLa cells. These findings underscore the potential of Compound H as an anticancer agent.

[0198] The anti-cancer studies for Compound I (Figure 22) illustrates its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a viability of 55.99% at 1 pM, which declines steadily to 8.28% at 1000 pM, indicating a significant cytotoxic effect. HT 29 cells show a dramatic response, beginning at 79.30% viability but dropping sharply to just 0.22% at the highest concentration, highlighting an extreme sensitivity to the compound. HeLa cells, starting at 64.11%, also experience a marked decline, ending at 12.85%. Overall, the results indicate that Compound I exerts a strong cytotoxic effect across all three cell lines, particularly affecting HT 29 cells the most. These findings underscore the potential of Compound I as an anticancer agent, in treating various cancer types.

[0199] The anti-cancer studies for Compound J (Figure 23) reveals its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells begin with a viability of 64.94% at 1 pM, showing a significant decrease to 5.68% at 1000 pM, indicating a pronounced cytotoxic effect. HT 29 cells display a similar trend, starting at 54.03% and declining sharply to 5.88% at the highest concentration, reflecting a high sensitivity to the compound. HeLa cells, with an initial viability of 80.17%, also experience a decline, ultimately reaching 7.41% at 1000 pM. Overall, the results demonstrate that Compound J exerts a potent cytotoxic effect across all three cell lines, with both MCF 7 and HT 29 cells being particularly impacted. These findings highlight the potential of Compound J as an effective anticancer agent. The anti-cancer studies for Compound K (Figure 24) shows its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a viability of 47.55% at 1 pM and exhibit a gradual decline to 7.35% at 1000 pM, indicating a significant cytotoxic effect. HT 29 cells begin with 48.37% viability and decrease to 15.51% at the highest concentration, showing notable sensitivity to the compound. HeLa cells, with an initial viability of 51.02%, also decline to 14.29%, suggesting they experience some level of toxicity as well. Overall, the results indicate that Compound K exerts a moderate cytotoxic effect across all three cancer cell lines, particularly affecting MCF 7 cells. These findings highlight Compound K's potential as an anticancer agent.

[0200] The anti-cancer studies for Compound L (Figure 25) illustrates its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells begin with a viability of 56.42% at 1 pM, with a steady decline to 13.44% at 1000 pM, indicating a significant dose-dependent cytotoxic effect. HT 29 cells show a similar pattern, starting at 48.27% and dropping to 13.24% at the highest concentration, highlighting their sensitivity to the compound. HeLa cells, starting at 52.48%, also experience a reduction in viability, ending at 14.26%. Overall, the results suggest that Compound L exerts a notable cytotoxic effect across all three cell lines, with both MCF 7 and HT 29 cells being particularly affected. These findings point to the potential of Compound L as an anticancer agent.

[0201] The anti-cancer studies for Compound M (Figure 26) reveals its effects on the viability of MCF 7, HT 29, and HeLa cancer cell lines. MCF 7 cells start with a viability of 63.61% at 1 pM, showing a notable decrease to 17.8% at 1000 pM, indicating a clear dose-dependent cytotoxic effect. HT 29 cells exhibit a high initial viability of 85.83%, which decreases to 52.27% at the highest concentration, suggesting a moderate sensitivity to the compound. In contrast, HeLa cells maintain the highest viability throughout, beginning at 93.81% and ending at 26.73%, indicating they are the most resilient of the three lines but still experience significant toxicity. Overall, these results suggest that Compound M has a potent cytotoxic effect, particularly on MCF 7 cells, and highlight its potential as an anticancer agent.

[0202] From the foregoing, it will be appreciated that various embodiments of the present disclosure have been described herein for purposes of illustration, and that various modifications may be made without departing from the scope and spirit of the present disclosure. Accordingly, the various embodiments disclosed herein are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

Claims

WE CLAIM:

1. A Novel Small-Molecule in overcoming tumor regression in Cancers, comprising of structure in accordance with formula 1Formula 1 or any derivative thereof, pharmaceutically acceptable salt thereof, or combination thereof wherein;Xi, X2, X3, X4 are is imino group or secondary amine group or methylene group or Methylidene group or oxo group or Oxygen atom;Y 1, Y2 is alkyl group or amino group or hydroxyl group;Z is secondary amine group or methylene group.

2. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is imino group;X2 is Oxo group;X3 is imino group;X4 is Oxygen atom;Y 1 is Methyl group;Y2 is Methyl group;Z is secondary amine group.

3. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule isCompound A4. The Novel Small-molecule of Formula 1 as claimed in claim 1 , wherein;Xi is imino group;X2 is methylidene group;X3 is Oxo group;X4 is Oxygen atom;Y 1 is Methyl group;Y2 is Amino group;Z is secondary amine group.

5. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is6. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is methylidene group;X2 is imino group;X3 is methylidene group;X4 is Oxygen atom;Y 1 is Methyl group;Y2 is Methyl group;Z is secondary amine group.

7. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule isThe Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is Oxo group;X2 is imino group;X3 is Oxo group;X4 is Oxygen atom;Y 1 is hydroxyl group;Y2 is hydroxyl group;Z is secondary amine group.

9. The Novel Small-molecule of Formula 1 as claimed in claim 1 , wherein the molecule isCompound D10. The Novel Small-molecule of Formula 1 as claimed in claim 1, whereinXi is methylidene group;X2 is imino group;X3 is Oxo group;X4 is secondary amine group;Yi is methyl group;Y2 is methyl group;Z is secondary amine group.

11. The Novel Small-molecule of Formula 1 as claimed in claim 1 , wherein the molecule isCompound E12. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is methylidene group;X2 is imino group;X3 is Oxo group;X4 is secondary amine group;Y 1 is hydroxyl group;Y2 is methyl group;Z is secondary amine group.

13. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule isCompound F14. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is methylidene group;X2 is imino group;X3 is Oxo group;X4 is secondary amine group;Yi is methyl group;Y2 is amino group;Z is secondary amine group.

15. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is16. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is Oxo groupX2 is methylidene groupX3 is Oxo groupX4 is secondary amine groupY 1 is hydroxyl groupY2 is hydroxyl groupZ is secondary amine group17. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is18. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is Oxo groupX2 is methylidene groupX3 is Oxo groupX4 is secondary amine groupY 1 is Methyl groupY2 is Methyl groupZ is secondary amine group19. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is20. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is Oxo group;X2 is methylidene group;X3 is Oxo group;X4 is methylene group;Yi is amino group;Y2 is amino group;Z is methylene group.

21. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is22. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is Oxo group;X2 is imino group;X3 is Oxo group;X4 is Oxygen atom;Yi is methyl group;Y2 is methyl group;Z is methylene group.

23. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is24. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is Oxo group;X2 is imino group;X3 is Oxo group;X4 is Oxygen atom;Yi is amino group;Y2 is amino group;Z is methylene group.

25. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is26. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein;Xi is Oxo group;X2 is methylidene group;X3 is methylidene group;X4 is Oxygen atom;Yi is methyl group;Y2 is methyl group;Z is methylene group.

27. The Novel Small-molecule of Formula 1 as claimed in claim 1, wherein the molecule is28. A pharmaceutical composition, comprising an effective amount of a molecule of any one of claims 1-27 or a stereoisomer or tautomer thereof and a pharmaceutically acceptable carrier thereof.

29. An article of manufacture, comprising: (i) an effective amount of a molecule of any one of claims 1-27 or a stereoisomer or tautomer thereof, or a pharmaceutical composition of claim 28; and (ii) instructions for use in treating cancer.

30. A kit, comprising: (i) an effective amount of a molecule of any one of claims 1-27, or a stereoisomer or tautomer thereof, or a pharmaceutical composition of claim 28; and (ii) instructions for use in treating cancer.

Images