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Synthesis and biological evaluation of 2-aminothiazole derivatives as antimycobacterial and antiplasmodial agents
Institution:1. Department of Chemistry, University of Cape Town, Private Bag X3, Rondebosch 7701, South Africa;2. MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Division of Medical Microbiology, Department of Clinical Laboratory Sciences, University of Cape Town, Rondebosch 7701, South Africa;3. Division of Pharmacology, Department of Medicine, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory 7925, South Africa;4. Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa;1. Department of Materials Science and Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan;2. Department of Machine Intelligence and Systems Engineering, Akita Prefectural University, 84-4 Aza Ebinokuchi, Tsuchiya, Yurihonjo City, Akita 015-0055, Japan;1. INMLCF, I.P. – North Branch, Portugal;2. CENCIFOR – Forensic Science Center, Portugal;3. Faculty of Medicine, University of Porto, Portugal;4. Biomedical Sciences Institute “Abel Salazar”, University of Porto, Portugal;1. Department of Pure and Applied Chemistry, Faculty of Science & Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan;2. Division of Ecosystem Research, Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan;3. AGC Seimi Chemical Co., Ltd., 3-2-10 Chigasaki-City, Kanagawa 253-8585, Japan
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.
Keywords:2-Amino-4-(2-pyridyl)thiazoles  Antimycobacterial  Antiplasmodial  Structure–activity relationship  Hit optimisation
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