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

Author(s)

da Silva, Thiago Sabino ; Souza, Matheus da Silva ; Andricopulo, Adriano Defini ; Coelho, Fernando

• Document type: Journal article
• Source: RSC ADVANCES; v. 13, n. 29, p. 7-pg., 2023-06-29.

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. (AU)

• FAPESP's process: 18/02611-0 - Post-Functionalization of Small Ply-functionalized Molecules: A Robust Approach to the Synthesis of New Structural Patterns with POtential Biological Activity
• Grantee: Fernando Antonio Santos Coelho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/00219-1 - Pathway toward catastrophe: cellular dynamics on hit-to-lead compound optimisation for current drug discovery pipelines
• Grantee: Matheus da Silva Souza
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/25289-7 - Discovery of new bioactive ligands with anticancer properties
• Grantee: Matheus da Silva Souza
• Support Opportunities: Scholarships in Brazil - Doctorate