具有对抗阴道毛滴虫耐药性潜力的新型甲硝唑-查尔酮共轭物。
Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.
作者信息
Anthwal Amit, Rajesh U Chinna, Rawat M S M, Kushwaha Bhavana, Maikhuri Jagdamba P, Sharma Vishnu L, Gupta Gopal, Rawat Diwan S
机构信息
Department of Chemistry, H.N.B. Garhwal University (A Central University), Srinagar (Garhwal), Uttarakhand 246174, India; Department of Chemistry, University of Delhi, Delhi 110007, India.
Department of Chemistry, University of Delhi, Delhi 110007, India.
出版信息
Eur J Med Chem. 2014 May 22;79:89-94. doi: 10.1016/j.ejmech.2014.03.076. Epub 2014 Mar 28.
Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 μg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.
滴虫病是最常见的可治愈性传播疾病（STD），它会增加感染病毒性传播疾病和艾滋病毒的风险。然而，一些阴道毛滴虫菌株已对甲硝唑（MTZ）产生耐药性，甲硝唑是美国食品药品监督管理局（FDA）批准用于治疗滴虫病的药物。在本研究中，为了获得对甲硝唑耐药的阴道毛滴虫具有更高活性的新分子，合成了22种甲硝唑查尔酮杂化物。所有新的杂化分子均对阴道毛滴虫有活性，对甲硝唑敏感和耐药菌株的活性水平各不相同。发现8种化合物（4a、4c、4d、4e、4f、4h、4q和4s）与标准药物活性相当，对甲硝唑敏感菌株的最低抑菌浓度（MIC）为1.56μg/ml。然而，化合物4e、4h和4m对耐药阴道毛滴虫的活性比甲硝唑高4倍，其中4e和4h对敏感和耐药菌株最有前景。
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