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

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.

Design, combinatorial synthesis and cytotoxic activity of 2-substituted furo[2,3-d]pyrimidinone and pyrrolo[2,3-d]pyrimidinone library.

A facile protocol was developed for the combinatorial synthesis of furo[2,3-d]pyrimidinone and pyrrolo[2,3-d]pyrimidinone library via a one-pot condensation, from 2-amino furans/pyrroles. Herein reported process required a similar reaction condition, providing mild access to two diverse series of natural product-like heterocycles. Both furo[2,3-d]pyrimidinones and pyrrolo[2,3-d]pyrimidinones were evaluated in vitro against a panel of human cancer cell lines including against human cancer HeLa (cervical), MCF-7 (breast) and HT-29 (colon) cell lines. Derivative 12n ((2-(4-chlorophenyl)-1-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrrolo[2,3-d]pyrimidin-4(1H)-one)) showed high activity (IC50 = 6.55 ± 0.31 µM) against the HeLa cell line. These products could be subjected to a various modification and therefore represent important skeletons for the anticancer drug discovery.