2. Academic Validation
  3. 2-Methyl-4/5-nitroimidazole derivatives potentiated against sexually transmitted Trichomonas: Design, synthesis, biology and 3D-QSAR study

2-Methyl-4/5-nitroimidazole derivatives potentiated against sexually transmitted Trichomonas: Design, synthesis, biology and 3D-QSAR study

  • Eur J Med Chem. 2016 Nov 29:124:820-839. doi: 10.1016/j.ejmech.2016.09.006.
Dhanaraju Mandalapu 1,  Bhavana Kushwaha 2,  Sonal Gupta 3,  Nidhi Singh 4,  Mahendra Shukla 5,  Jitendra Kumar 6,  Dilip K Tanpula 7,  Satya N Sankhwar 8,  Jagdamba P Maikhuri 2,  Mohammad I Siddiqi 4,  Jawahar Lal 5,  Gopal Gupta 9,  Vishnu L Sharma 10
Affiliations

Affiliations

  • 1 Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
  • 2 Endocrinology Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
  • 3 Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India.
  • 4 Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
  • 5 Pharmacokinetic & Metabolism Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
  • 6 Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, 229 010, India.
  • 7 Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, 229 010, India.
  • 8 Department of Urology, King George Medical University, Lucknow, 226003, India.
  • 9 Endocrinology Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India.
  • 10 Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India. Electronic address: vl_sharma@cdri.res.in.
PMID: 27643640 DOI: 10.1016/j.ejmech.2016.09.006
Abstract

Trichomoniasis is the most prevalent, non-viral sexually transmitted diseases (STD) caused by amitochondriate protozoan Trichomonas vaginalis. Increased resistance of T. vaginalis to the marketed drug Metronidazole necessitates the development of newer chemical entities. A library of sixty 2-methyl-4/5-nitroimidazole derivatives was synthesized via nucleophilic ring opening reaction of epoxide and the efficacies against drug-susceptible and -resistant Trichomonas vaginalis were evaluated. All the molecules except two were found to be active against both susceptible and resistant strains with MICs ranging 8.55-336.70 μM and 28.80-1445.08 μM, respectively. Most of the compounds were remarkably more effective than the standard Metronidazole. This study analyzes the in vitro and in vivo activities of the new 5-nitroimidazoles, which were found to be safe against human cervical HeLa cells with good selectivity index. The exploration of SAR by the synthesis of four different prototypes and 3D-QSAR study has shown the importance of prototype 1 over Other prototypes.

Keywords

4/5-Nitroimidazoles; Anti-Trichomonas; Dithiocarbamate; Hybridization; Resistant Trichomonas.

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