9 results about "Epipodophyllotoxin" patented technology

The present invention concerns a novel enantiomer of 9-(3-fluorophenyl)-5-(2- hydroxyethyl)-6,9-dihydro-[l,3]dioxolo[4,5-g]furo[3,4-b]quinolin-8(5H)-one (SU056), as well as pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising it, and its uses in medical treatments, particularly including cancer treatments.

The invention relates to the technical field of biology, in particular to a cytochrome P450 BM3 variant and application of the cytochrome P450 BM3 variant in hydroxylation of (-)-deoxypodophyllotoxin. The present invention provides a highly active P450 BM3 variant capable of catalyzing the conversion of (-)-deoxypodophyllotoxin into (-)-epipodophyllotoxin. Tests show that the engineered natural cytochrome P450 monooxygenase variant can efficiently catalyze a C ring C4 position of a (-)-deoxypodophyllotoxin molecular ring skeleton to realize efficient beta hydroxylation reaction, so that a derivative with medicinal value is generated, the reaction condition is mild, and the product shows excellent regioselectivity and stereoselectivity.

This invention belongs to the field of biomedical technology, specifically relating to phosphodiesterase 2 (PDE2) activity inhibitors. Six PDE2 activity inhibitors were screened, providing six compounds: sanguisorbin, Picropodophyllol, aristolochic acid D, Malabaricone A, tetradehydropodophyllotoxin, and Roseoflavin. These compounds can be used to prepare PDE2 activity inhibitor drugs. Biological experimental methods were used to detect and verify the activity, resulting in effective PDE2 enzyme inhibitors. The IC50 level of these inhibitors was measured. 50 It exhibits good PDE2 enzyme inhibition effect.

The application discloses an E2 fusion protein, a coding gene thereof and application of the E2 fusion protein. The E2 fusion protein is fused by an E2 protein and a label; the amino acid sequence of the E2 protein is shown as positions 1 to 365 from the N-terminal end in SEQ ID NO:1. Experiments prove that the E2 protein has a helicase activity, and an anti-human papillomavirus drug, a podophyllotoxin, can inhibit the helicase activity of the E2 protein. Therefore, the E2 protein is a target of the action of the podophyllotoxin, and the E2 protein can also be used as a target for screening the anti-human papillomavirus drug. The application has important application value in the process of screening the anti-human papillomavirus drug.

The invention relates to application of 4 '-demethyl epipodophyllotoxin or a medicinal derivative thereof in depression resistance, and belongs to the technical field of biological medicines. Depression is a serious nervous and mental disease and affects millions of people in the world. Major depression is the most common mental disorder and is also one of the main causes of global disability. Depression is considered to be a complex disease caused by interaction of genetic, physiological, psychological and environmental factors. It is found that the novel antidepressant drug capable of treating depression has great significance. A per2- / -mutant zebrafish depression model is utilized to perform drug screening on traditional Chinese medicine monomers, and finally, 10 mu M of 4 '-demethylepipodophyllotoxin has an anti-depression characteristic and can effectively improve the depression-like phenotype of per2- / -mutant zebrafish. A medicinal plant podophyllotoxin from which 4 '-demethyl epipodophyllotoxin is extracted is safe and non-toxic, and no report about 4'-demethyl epipodophyllotoxin depression resistance exists at present.

The invention discloses a podophyllotoxin-loaded nano-drug as well as a preparation method and application thereof. The nano-drug is of a core-shell structure, podophyllotoxin is entrapped by lecithin to form a hydrophobic core, and modified chitosan is coated on the surface to serve as a shell layer. The preparation method comprises the following steps: injecting an ethanol solution of lecithin and podophyllotoxin into an acetic acid aqueous solution of modified chitosan, incubating and centrifuging to obtain the modified chitosan, and the preparation process is simple and convenient. The water solubility and the stability of podophyllotoxin can be remarkably improved through the prepared nano-drug, the anti-tumor immune response of a body is activated while efficient chemotherapy is achieved through the immunologic adjuvant function of the modified chitosan, the synergistic treatment effect is generated, and the nano-drug has the excellent inhibition effect on solid tumors.

This invention discloses a podophyllotoxin-9-fluorenylmethanol small molecule prodrug nanoparticle, its preparation method, and its applications. The podophyllotoxin-9-fluorenylmethanol small molecule prodrug co-assembled nanoparticles are either polyethylene glycol-modified podophyllotoxin-9-fluorenylmethanol small molecule prodrug co-assembled with gossypol, or podophyllotoxin-9-fluorenylmethanol small molecule prodrug co-assembled with gossypol and loaded with hydrophobic fluorescent substances. The podophyllotoxin-9-fluorenylmethanol small molecule prodrug is prepared by linking podophyllotoxin and its compounds with 9-fluorenylmethanol via disulfide bonds. This invention is the first to construct a carrier-free hybrid nanoassembly of gossypol and PPT oxidation-sensitive prodrug. Gossypol-mediated prodrug co-assembled nanoparticles can be used for precision cancer chemotherapy in tumor treatment, precisely achieving PPT "enhancement," improving the therapeutic efficiency of PPT prodrugs, opening an ultra-low-dose chemotherapy window for PPT, and solving the problems of delayed and insufficient prodrug activation.

The invention provides a podophyllotoxin amino acid derivative as shown in a formula (I), an isomer, a solvate or a hydrate or a pharmaceutically acceptable salt thereof, a preparation method and application of the podophyllotoxin amino acid derivative. Structural modification is performed according to different positions of a natural podophyllotoxin structure, and different amino acid side chains are introduced to perform systematic structural design and activity screening, and results show that compared with a clinical drug such as etoposide, the podophyllotoxin amino acid derivative obtained by an amino acid derivation strategy has the advantages that the podophyllotoxin amino acid derivative has a good application prospect. The inhibitory activity on different kinds of malignant tumors is greatly improved, expected improvement is achieved in the aspect of safety, and the compound can be used as a candidate drug for developing potential drugs for treating different tumors.

The invention discloses a programmed cascade response nano drug delivery platform as well as a preparation method and application thereof. Raft-base PEG-5000 is used as an initiator and is respectively subjected to polymerization reaction with an acid response monomer C7A and a blood vessel disrupting agent DMXAA connected through an ester bond or podophyllotoxin connected through an oxalate bond to prepare two random copolymers. The copolymer is dissolved in tetrahydrofuran, the solution is slowly and dropwise added into a phosphate buffer solution containing glucose oxidase, a vesicle structure is formed through self-assembly, wrapping of the glucose oxidase is achieved, and therefore the nano-drug delivery platform with the programmed cascade response characteristic is constructed. According to the invention, through a programmed cascade response mechanism, synergistic cooperation of time sequence regulation and control of drug release and a treatment function is realized, and the drug has multiple stimulation responsiveness, drug effect controllability and immunoregulation ability, is suitable for multi-mode combined treatment of solid tumors, and has a clear technical implementation path and application value.