Furo[2,3-d]pyrimidines as Mackinazolinone/Isaindigotone Analogs: Synthesis, Modification, Antitumor Activity, and Molecular Docking Study

Abstract

The chemical transformation of the tricyclic furo[2,3-d]pyrimidines was performed under isosteric and scaffold-hopping strategies focusing on the synthesis of its arylidene and imine-containing derivatives. Naturally-occurring alkaloids mackinazolinone and isaindigotone were as templates of target heterocycles. Synthesized compounds evaluated for their antitumor activity on human cancer cervical HeLa, breast MCF-7, and colon HT-29 cell lines. Four compounds: 8c, 8e, 10b, and 10c demonstrated potency against HeLa and HT-29 cell lines, and IC₅₀ values were between 7.37-13.72 μM, respectively. The molecular docking results showed that compounds 8c and 10b had good binding and high matching with the target EGFR protein.

Keywords: EGFR; antitumor activity; arylidene; furo[2,3-d]pyrimidine; mackinazolinone.