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Chalcone-Thiazole Hybrids: Rational Design, Synthesis, and Lead Identification against 5-Lipoxygenase.

ABSTRACT: A hybrid pharmacophore approach is used to design and synthesize novel chalcone-thiazole hybrid molecules. Herein, thiazole has been hybridized with chalcone to obtain a new class of 5-LOX inhibitors. In vitro biological evaluation showed that most of the compounds were better 5-LOX inhibitors than the positive control, Zileuton (IC50 = 1.05 ± 0.03 ?M). The best compounds in the series, namely, 4k, 4n, and 4v (4k: IC50 = 0.07 ± 0.02 ?M, 4n: IC50 = 0.08 ± 0.05 ?M, 4v: 0.12 ± 0.04 ?M) are found to be 10 times more active than previously reported 2-amino thiazole (2m: IC50 = 0.9 ± 0.1 ?M) by us. Further, 4k has redox (noncompetitive) while 4n and 4v act through a competitive inhibition mechanism. SAR indicated that the presence of methoxy/methyl either in the vicinity of chalcone or both thiazole and chalcone contributed to the synergistic inhibitory effect.

SUBMITTER: Sinha S

PROVIDER: S-EPMC6792153 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Chalcone-Thiazole Hybrids: Rational Design, Synthesis, and Lead Identification against 5-Lipoxygenase.

Sinha Shweta S Manju S L SL Doble Mukesh M

ACS medicinal chemistry letters 20190909 10

A hybrid pharmacophore approach is used to design and synthesize novel chalcone-thiazole hybrid molecules. Herein, thiazole has been hybridized with chalcone to obtain a new class of 5-LOX inhibitors. In vitro biological evaluation showed that most of the compounds were better 5-LOX inhibitors than the positive control, Zileuton (IC50 = 1.05 ± 0.03 μM). The best compounds in the series, namely, 4k, 4n, and 4v (4k: IC50 = 0.07 ± 0.02 μM, 4n ...[more]

PMID: 31620227

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