New antiprotozoal agents: Synthesis and biological evaluation of different 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives

  • Bioorg Med Chem Lett. 2017 Feb 1;27(3):460-465. doi: 10.1016/j.bmcl.2016.12.043.
Mohammad Fawad Ansari  1 ,  Faisal Hayat  2 ,  Afreen Inam  1 ,  Fatima Kathrada  3 ,  Robyn L van Zyl  3 ,  Maureen Coetzee  4 ,  Kamal Ahmad  5 ,  Dongyun Shin  2 ,  Amir Azam  6
Affiliations
  • 1. Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
  • 2. College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, South Korea.
  • 3. Pharmacology Division, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa; WITS Research Institute for Malaria (WRIM), Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa.
  • 4. WITS Research Institute for Malaria (WRIM), Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa; Vector Control Reference Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
  • 5. Centre for Interdisciplinary Science, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
  • 6. Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address: [email protected].
PMID: 28027871 DOI: 10.1016/j.bmcl.2016.12.043
Abstract

In an endeavor to develop efficacious antiprotozoal agents 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives (5-14) were synthesized, characterized and biologically evaluated for antiprotozoal activity. The compounds were screened in vitro against the HM1: IMSS strain of Entamoeba histolytica and NF54 chloroquine-sensitive strain of Plasmodium falciparum. Among the synthesized compounds six exhibited promising antiamoebic activity with IC50 values (0.14-1.26μM) lower than the standard drug metronidazole (IC50 1.80μM). All nine compounds exhibited antimalarial activity (IC50 range: 1.42-19.62μM), while maintaining a favorable safety profile to host red blood cells. All the compounds were less effective as an antimalarial and more toxic (IC50 range: 14.67-81.24μM) than quinine (IC50: 275.6±16.46μM) against the human kidney epithelial cells. None of the compounds exhibited any inhibitory effect on the viability of Anopheles arabiensis mosquito larvae.

Keywords
Amoebiasis; Entamoeba histolytica; MTT-assay; Metronidazole; Plasmodium falciparum; Thioredoxin reductase.