Design, synthesis and antimalarial evaluation of novel thiazole derivatives. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Bueno, José María; Carda, Miguel; Crespo, Benigno; Cuñat, Ana Carmen; de Cozar, Cristina; León, María Luisa; Marco, J. Alberto; Roda, Nuria; Sanz-Cervera, Juan F.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 16(2016)
• Page Start: 3938
• Page End: 3944
• Publication Date: 2016-08-15
• Subjects: CNMZIXJOGDMBQE-UHFFFAOYSA-N -- RWEYRAILMRXFKJ-UHFFFAOYSA-N -- BMGLXRVZDUHLCH-UHFFFAOYSA-N -- NOQPRGXNLLFDIU-UHFFFAOYSA-N -- WSGZTLQEJWVJLW-UHFFFAOYSA-N -- CRNDQQKFLYNSJC-UHFFFAOYSA-N -- CPYIIDRFIFTEHM-UHFFFAOYSA-N; Malaria -- Antimalarials -- Synthesis -- Thiazoles -- Structure–activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.07.010
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: As part of our medicinal chemistry program's ongoing search for compounds with antimalarial activity, we prepared a series of thiazole analogs and conducted a SAR study analyzing their in vitro activities against the chloroquine-sensitive Plasmodium falciparum 3D7 strain. The results indicate that modifications of the N -aryl amide group linked to the thiazole ring are the most significant in terms of in vitro antimalarial activity, leading to compounds with high antimalarial potency and low cytotoxicity in HepG2 cell lines. Furthermore, the observed SAR implies that non-bulky, electron-withdrawing groups are preferred at ortho position on the phenyl ring, whereas small atoms such as H or F are preferred at para position. Finally, replacement of the phenyl ring by a pyridine affords a compound with similar potency, but with potentially better physicochemical properties which could constitute a new line of research for further studies.