New application of benzo [C] phenanthridine and protopine in producing overriding resistant bacterium medicament

A technology for drug-resistant bacteria and uses, which can be used in antibacterial drugs, pharmaceutical formulations, medical preparations containing active ingredients, etc., and can solve problems such as lack of documentation

Inactive Publication Date: 2008-06-11
成都军区昆明总医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The above documents related to the preparation and application research of benzo[C]phenanthridine and prototropine derivatives are limited to antitumor, antiplatelet aggregation, antiarrhythmia and insecticidal effects; although antibacterial, fungal and antibacterial effects have also been mentioned. Viral effects, but there is no literature suggesting the effects of benzo[C]phenanthridine and prototropine alkaloids and their derivatives on MRSA and ESBLs-producing bacteria
[0007] Throughout the reports at home and abroad, there is no patent that specifically refers to the anti-drug-resistant bacteria of the benzo[C]phenanthridine alkaloids and prototropine alkaloids involved in the present invention

Method used

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  • New application of benzo [C] phenanthridine and protopine in producing overriding resistant bacterium medicament
  • New application of benzo [C] phenanthridine and protopine in producing overriding resistant bacterium medicament
  • New application of benzo [C] phenanthridine and protopine in producing overriding resistant bacterium medicament

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: Extraction and separation of monomeric alkaloids 1-4 from celandine.

[0031]Get the whole herb of celandine (Chelidonium majus) and adjust slightly according to the method introduced in references [2, 3]: 5 kg of medicinal materials are extracted three times with 70% ethanol containing 5% acetic acid, and the extracts are combined, concentrated and steamed under reduced pressure. Most of the ethanol was removed, and the acid water extract was treated with a conventional acid-base method. First, 5% hydrochloric acid was added to PH2, and extracted with petroleum ether. The resulting acid water layer (S-1) was extracted with chloroform to obtain 23g (L-1). Silica gel column chromatography, petroleum ether: chloroform (10:0 ~ 10:1.5) gradient elution, to give chelidonine (4 = 1.86g) and dihydrochelerythrine (2 = 45mg).

[0032] The above acidic aqueous layer (S-2) extracted with chloroform was allowed to stand, and the precipitate was collected by filtration, r...

Embodiment 2

[0033] Example 2: Conversion from quaternary ammonium benzo[C]phenanthridine alkaloids to tertiary amine benzo[C]phenanthridine alkaloids.

[0034] According to the method of reference [4], take chelerythrine hydrochloride (20 mg, 0.052 mM) and dissolve it in 15 ml of 10% dilute hydrochloric acid, add 0.3 g of zinc powder under stirring at room temperature, continue stirring overnight, and extract the reaction mixture with chloroform (60ml×3), wash the extract with a small amount of acidic water (10% dilute hydrochloric acid), then wash with water until neutral, recover chloroform, and recrystallize the residue with ethanol to obtain 14 mg of dihydrochelerythrine (yield 77%) . The obtained physical and chemical constants and spectral data are consistent with those obtained by extraction and separation of dihydrochelerythrine.

[0035] The conversion of other quaternary ammonium benzo[C]phenanthridine alkaloids into tertiary amine benzo[C]phenanthridine alkaloids can be prepar...

Embodiment 3

[0036] Example 3: Physicochemical and Spectroscopic Data of Monomeric Compounds.

[0037] Chelidonine hydrochloride (1): [C 21 h 18 NO 4 ] + , yellow needle crystal, mp 201-202 ℃, bismuth iodide potassium reaction is positive. IR KBr max (cm -1 ): 3380, 2920, 2824, 1642 (C≡N + ), 1575, 1450, 1364, 1250, 1100, 1035 (C-O-C), 970, 875, 825; UV (nm, logε): 228 (4.49), 274sh (4.54), 282 (4.62), 320 (4.26), 346sh(3.55); EIMS: m / z 348[M] + (100), 333(12), 318(5), 307(6), 290(5), 167(4), 154(38), 136(31), 124(4). 1 H-NMR (400MHz, DMSO-d 6 ): 4.07 (3H, s, OMe), 4.13 (3H, s, 3H, s, OMe), 4.93 (3H, s, 3H, s, N-Me), 6.22 (2H, s, 2H, s, - OCH 2 O-), 7.83 (1H, s, 1H, s, H-1), 8.24 (1H, d, J=9.0Hz, H-9), 8.26 (1H, s, H-4), 8.29 (1H, d, J=9.0 Hz, H-9), 8.80 (2H, d, J=9.0 Hz, H-11), 10.06 (1H, s).

[0038] Dihydrochelerythrine (2): off-white crystal, C 21 h 19 NO 4 , mp164-165 ° C, bismuth iodide potassium reaction was positive. EIMS: 349[M] + (100), 348 (80), 334 [M-Me] + (1...

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Abstract

The invention relates to a new application of benzo [C] phenanthridine as formula I and original tropine alkaloid for preparing anti-drug-resistant bacterial drug, wherein R1-R10, R12-R15 are hydrogen and hydroxyl groups, cycloalkyl or alkyl groups with 1-12 carbon atoms, alkox or acyloxy groups, benzyloxy, chlorine or other halide atoms, amido, methylol, aldehydo, aldehydo, acetonyl, carboxy group, mesyloxy, 4-methyl-benzene sulfonyl oxygen group, aryl sulfonyl oxygen group, biphenyl phosphine acyloxy and -OCONH2, R11 is hydrogen, methyl or oxygen atom, R5 and R6 (or R15 of the formula I), R14 and R15 are formed with double bonds, R12 or R13 and nearby N atoms are formed with double bonds, N atom can be tertiary or quaternary N type, the substituents of nearby carbons of R1-R10 can have dioxolane structure. The inventive alkaloid can effectively restrain and kill drug-resistant bacterials as MRSA and ESBLs.

Description

technical field [0001] The invention relates to the use of benzo[C]phenanthridine and protopine alkaloids in the preparation of anti-drug-resistant bacteria drugs. Background technique [0002] The emergence and spread of bacterial resistance have seriously affected the development of human health. With the widespread use of antibiotics, more and more bacteria are resistant to commonly used antibiotics, and the degree of drug resistance is increasing. Bacterial resistance often renders treatment ineffective, infection worsens, and even death. At the same time, ineffective treatment also increases medical expenses, including frequent admissions of patients and prolongation of hospitalization, thereby increasing the burden on patients and society. Since Jevons first discovered the first strain of methicillin-resistant staphylococcus aureus (MRSA) in the UK in 1961, the positive rate of MRSA in clinical isolation at home and abroad has been increasing, reaching up to 80%. Co...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D491/04C07D491/14C07D455/03A61K31/4375A61K31/4353A61P31/04
Inventor 左国营徐贵丽张青王根春高锁孟凡堰尹玉琴张云玲陈燕陈芳孔繁凡
Owner 成都军区昆明总医院
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