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.

Furo, Pyrano, and Pyrido[2,3‐d]Pyrimidines: A Comprehensive Review of Synthesis and Medicinal Applications

“…Among them, two compounds V and VII showed potency against HeLa and HT‐29 with IC50 values ranging from 7.37 μM to 13.72 μM. Molecular docking results indicated that compounds V and VII exhibited good binding and high matching with the target EGFR protein [31] . Moreover, The research by Mousavi et al.…”

“…Molecular docking results indicated that compounds V and VII exhibited good binding and high matching with the target EGFR protein. [31] Moreover, The research by Mousavi et al (2023) presents a green and efficient method for the synthesis of drug-like furo[2,3-d]pyrimidines. These compounds were tested for their inhibitory properties against both SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) MPro (Main Protease) and PLPro (Papain-Like Protease).…”

“…In 2022, Song and colleagues [31] conducted a study in which they investigated two new series of furo[2,3‐ d ]pyrimidines containing arylidene 184 – 185 and imine fragments. These compounds were designed using isosteric and scaffold‐hopping strategies, with natural substances mackinazolinone and isaindigotone serving as templates for the target heterocycles.…”

Synthesis of tricyclic pyrazolopyrimidine arylidene ester derivatives and their cytotoxic and molecular docking evaluations

“…Our research team has been dedicated to developing diverse antitumor compounds integrated with tricyclic heterocycles [3], and have achieved encouraging results [4] using natural products such as deoxyvasicinone [5] and mackinazolinone as templates. The benzene ring structure in quinazoline was replaced with a fivemembered heterocyclic ring, and eight new tricyclic heterocyclic pyrimidines were synthesized based on principles of electron isosteric and skeletal transition in drug design [6][7][8][9][10][11][12][13].…”