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Synthesis, Inhibitory Activity, and In Silico Modeling of Selective COX-1 Inhibitors with a Quinazoline Core.

ABSTRACT: Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with the discovery of COX-1 upregulation in various cancers and the cardioprotective role of COX-1 in control of thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series of quinazoline derivatives were prepared and tested for their potential inhibitory activity toward COX-1 and COX-2. Of the prepared compounds, 11 exhibited interesting COX-1 selectivity, with 8 compounds being totally COX-1-selective. The IC₅₀ value of the best quinazoline inhibitor was 64 nM. The structural features ensuring COX-1 selectivity were elucidated using in silico modeling.

SUBMITTER: Dvorakova M

PROVIDER: S-EPMC8040043 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Synthesis, Inhibitory Activity, and <i>In Silico</i> Modeling of Selective COX-1 Inhibitors with a Quinazoline Core.

Dvorakova Marcela M Langhansova Lenka L Temml Veronika V Pavicic Antonio A Vanek Tomas T Landa Premysl P

ACS medicinal chemistry letters 20210312 4

Selective cyclooxygenase-1 (COX-1) inhibition has got into the spotlight with the discovery of COX-1 upregulation in various cancers and the cardioprotective role of COX-1 in control of thrombocyte aggregation. Yet, COX-1-selective inhibitors are poorly explored. Thus, three series of quinazoline derivatives were prepared and tested for their potential inhibitory activity toward COX-1 and COX-2. Of the prepared compounds, 11 exhibited interesting COX-1 selectivity, with 8 compounds being totally ...[more]

PMID: 33854702

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