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N-alkyl/aralkyl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbodithioate derivatives to tackle resistant trichomoniasis


Trichomoniasis is the most common sexually transmitted infection of the urogenital tract predisposing to HIV infection and cervical cancer in women. The development of resistance against metronidazole (MTZ, the only effective approved drug for trichomoniasis), thrown a challenge to find out alternate medication.


To Design and synthesize novel agents to be effective against MTZ resistant trichomoniasis.


Benzenepropanamines and selective serotonin reuptake inhibitor (SSRI) antidepressants viz. fluoxetine and paroxetine, possibly interacting with sulfhydryl groups present over Trichomonas.[1] Alongside dithiocarbamate nucleus is a well established pharmacophore possessing anti-Trichomonas activity.[2] In our ongoing efforts a series of benzenepropanamine-dithiocarbamate hybrids (14-28) as N-alkyl/aralkyl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbodithioates have been designed, synthesized and evaluated for their anti-Trichomonas activity profile to be useful as vaginal microbicide. All compounds were tested for safety through cytotoxic assay against human cervical cell line (Hela) and compatibility with vaginal flora, Lactobacillus.


2-(pyrrolidin-1-yl)ethyl 4-(3-oxo-3-phenylpropyl)piperazine-1-carbodithioate (Compound 17) was the most promising compound with anti–Trichomonas activity (MIC, 39.79 µM against MTZ susceptible and MIC, 79.92 µM against resistant strain) in comparison to MTZ (MIC, 19.71 µM against MTZ susceptible and MIC, 292.80 µM against resistant strain). Six compounds (14, 15, 17, 19, 21, 22, MIC 79.92–178.57 µM) were more active against resistant strain in comparison to Metronidazole. The extreme safety profile against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus) supported its suitability for vaginal application.


A novel molecule to be effective against resistant Trichomoniasis in comparison to MTZ has been identified to be developed for topical application emphasizing on improvement of women reproductive health.

Disclosure of interest

None declared.


  1. Kumar Kiran S.T.V.S., et al: Bioorg. Med. Chem. 2006, 14: 6593-10.1016/j.bmc.2006.06.003.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Bala, V., Kushwaha, B., Gupta, G. et al. N-alkyl/aralkyl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbodithioate derivatives to tackle resistant trichomoniasis. Antimicrob Resist Infect Control 4 (Suppl 1), P223 (2015).

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