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 IC 50 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.