Quaternary ammonium chalcone derivatives with anti-drug-resistant bacteria activity, preparation method and application thereof

Abstract

The invention belongs to the technical field of medicinal chemistry, and discloses quatemary ammonium chalcone derivatives resistant to drug-resistance bacteria activities, a preparation method and application of the quatemary ammonium chalcone derivatives. A structural formula is as shown in the description. Proved by invitro antibacterial activity experiments and erythrocyte hemolytic experiments, a large part of compounds in the series of the derivatives have great antibacterial effects and selections on staphylococcus aureus and colonic enterococcus faecalis of gram-positive bacteria, escherichia coli and pseudomonas aeruginosa of gram-negative bacteria. The selected part of compounds show great antimicrobial activities on a plurality of 'superbacteria' including methicillin-resistant staphylococcus aureus (MRSA), vancomycin resistant enterococcus (VRE), carbapenem-resistant enterobacteriaceae (CRE) and new delhi metallo (NDM) carrying NDM genes, and especially show excellent activities on the MRSA. Proved by invitro erythrocyte toxicity experiments, the series of compounds are low in erythrocyte toxicity and can be adopted as new anti-microbial drug candidates.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and discloses quaternary ammonium chalcone derivatives with anti-drug-resistant bacteria activity, their preparation method and their application as a class of novel anti-drug-resistant bacteria drugs. Background technique [0002] In the 1930s, the world's first antibiotic, penicillin, came out, bringing good news to countless patients and surgeons. With the development of science and technology, coupled with people's misunderstanding of antibiotics, the overuse of antibiotics has been accelerated, leading to the increasingly serious problem of bacterial acquired drug resistance, and the proportion of drug-resistant bacteria has increased year by year. According to the national bacterial drug resistance surveillance results of the Ministry of Health in the first half of 2016, bacterial drug resistance tests in 30 hospitals across the country showed that MRSA is resistant to 75% of co...

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Problems solved by technology

Due to its positive charge, it can combine with the anions on the surface of the bacterial membrane to enhance the binding ability with the bacterial membrane. However, due to the high production cost of natural antimicrobial peptides, it is not easy to mass-produce, and it is easy to be degraded in the body. Some antimicrobial peptides are highly toxic and have weak selectivity.

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