Novel metronidazole–chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis

• All hybrid molecules were found active against susceptible and resistant strain of Trichomonas vaginalis.
• Eight compounds were found as potent as standard drug against metronidazole susceptible strain of T. vaginalis.
• Five, seven and three compounds were found equipotent, 2-fold and 4-fold active than standard drug respectively.
• In vitro cytotoxicity of two most active compounds is much above than MIC values.

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.

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