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Discovery of indolizine lactones as anticancer agents and their optimization through late-stage functionalization.

ABSTRACT: Indolizines fused with a seven-member lactone ring were identified as a promising scaffold in the search for new anticancer agents. Through a modular synthetic sequence, a library of cis and trans indolizines lactones had their antiproliferative activity evaluated against hormone-refractory prostate DU-145 and triple-negative breast MDA-MB-231 cancer cell lines. A methoxylated analogue was identified as an initial hit against MDA-MB-231 and late-stage functionalization of the indolizine core led to analogues within potencies up to twenty times higher than the parent precursor.

SUBMITTER: da Silva TS

PROVIDER: S-EPMC10321224 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Discovery of indolizine lactones as anticancer agents and their optimization through late-stage functionalization.

da Silva Thiago Sabino TS da Silva Souza Matheus M Andricopulo Adriano Defini AD Coelho Fernando F

RSC advances 20230601 29

Indolizines fused with a seven-member lactone ring were identified as a promising scaffold in the search for new anticancer agents. Through a modular synthetic sequence, a library of <i>cis</i> and <i>trans</i> indolizines lactones had their antiproliferative activity evaluated against hormone-refractory prostate DU-145 and triple-negative breast MDA-MB-231 cancer cell lines. A methoxylated analogue was identified as an initial hit against MDA-MB-231 and late-stage functionalization of the indol ...[more]

PMID: 37416908

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