title: Synthesis and biological evaluation of 2-aminothiazole derivatives as antimycobacterial and antiplasmodial agents.
abstract: A series of compounds derived from the 2-amino-4-(2-pyridyl) thiazole scaffold was synthesized and tested for in vitro antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain, antiplasmodial activity against the chloroquine sensitive NF54 Plasmodium falciparum strain and cytotoxicity on a mammalian cell line. Optimal antimycobacterial activity was found with compounds with a 2-pyridyl ring at position 4 of the thiazole scaffold, a substituted phenyl ring at the 2-amino position, and an amide linker between the scaffold and the substituted phenyl. The antiplasmodial activity was best with compounds that had the phenyl ring substituted with hydrophobic electron withdrawing groups.
authors.affiliation: Department of Chemistry, University of Cape Town, Private Bag X3, Rondebosch 7701, South Africa.
authors.forename: Faith
authors.initials: F
authors.lastname: Mjambili
authors.affiliation: Department of Chemistry, University of Cape Town, Private Bag X3, Rondebosch 7701, South Africa.
authors.forename: Mathew
authors.initials: M
authors.lastname: Njoroge
authors.affiliation: MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Division of Medical Microbiology, Department of Clinical Laboratory Sciences, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Krupa
authors.initials: K
authors.lastname: Naran
authors.affiliation: Division of Pharmacology, Department of Medicine, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory 7925, South Africa.
authors.forename: Carmen
authors.initials: C
authors.lastname: De Kock
authors.affiliation: Division of Pharmacology, Department of Medicine, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory 7925, South Africa.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.affiliation: MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Division of Medical Microbiology, Department of Clinical Laboratory Sciences, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Valerie
authors.initials: V
authors.lastname: Mizrahi
authors.affiliation: MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Division of Medical Microbiology, Department of Clinical Laboratory Sciences, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Digby
authors.initials: D
authors.lastname: Warner
authors.affiliation: Department of Chemistry, University of Cape Town, Private Bag X3, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa. Electronic address: kelly.chibale@uct.ac.za.
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D013844:Thiazoles; C004483:2-aminothiazole
keywords: 2-Amino-4-(2-pyridyl)thiazoles; Antimycobacterial; Antiplasmodial; Hit optimisation; Structure–activity relationship