Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives

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Artigo de periódico

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Membros da banca

Resumo

A series of novel isocoumarin derivatives were synthesized using Castro–Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 μg mL−1). This compound represents a promising matrix for developing new antiproliferative agents.

Abstract

Assunto

Química farmacêutica, Sintese, Hidrogenação, Células - Proliferação, Compostos orgânicos

Palavras-chave

Isocoumarin, 3,4-Dihydroisocoumarin, Castro–Stephens reaction, Antiproliferative

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Endereço externo

https://www.sciencedirect.com/science/article/pii/S0223523416300599

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