title: New antiprotozoal agents: Synthesis and biological evaluation of different 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives.
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 IC50values (0.14-1.26μM) lower than the standard drug metronidazole (IC501.80μM). All nine compounds exhibited antimalarial activity (IC50range: 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 (IC50range: 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.
authors.affiliation: Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
authors.forename: Mohammad Fawad
authors.initials: MF
authors.lastname: Ansari
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, South Korea.
authors.forename: Faisal
authors.initials: F
authors.lastname: Hayat
authors.affiliation: Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
authors.forename: Afreen
authors.initials: A
authors.lastname: Inam
authors.affiliation: 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.
authors.forename: Fatima
authors.initials: F
authors.lastname: Kathrada
authors.affiliation: 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.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: van Zyl
authors.affiliation: 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.
authors.forename: Maureen
authors.initials: M
authors.lastname: Coetzee
authors.affiliation: Centre for Interdisciplinary Science, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
authors.forename: Kamal
authors.initials: K
authors.lastname: Ahmad
authors.affiliation: College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, South Korea.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address: amir_sumbul@yahoo.co.in.
authors.forename: Amir
authors.initials: A
authors.lastname: Azam
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000737:chemistry*; D004748:Entamoeba histolytica / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000962:Antimalarials; D000981:Antiprotozoal Agents; D010879:Piperazines; D015800:Protozoan Proteins; D000077489:Piperazine; D002738:Chloroquine; D013880:Thioredoxin-Disulfide Reductase
keywords: Amoebiasis; Entamoeba histolytica; MTT-assay; Metronidazole; Plasmodium falciparum; Thioredoxin reductase