Rational design, synthesis, biological evaluation and molecular docking studies of chromone-pyrimidine derivatives as potent anti-cancer agents

A new series of pyrimidine based chromone hybrids were synthesized from 7-methoxy-8-formylchromone using facile multi-component modified Biginelli reaction. All the newly synthesized compounds were characterized and evaluated for their in vitro anti-cancer activity against three cancer cell lines, human cervical (HeLa), lung (A549), myelogenous leukaemia (K562) cancer cell lines and on a normal cell line(HEK-293) for the selectivity reference. Among them, compounds 6a, 6b, 6c, 6f, 8a and 8b exhibited potent anti-cancer activities against A549, HeLa and K562 cell lines with IC50 values in micro molar range. The compounds 8a-8e were displayed selective anti-cancer activity against K562 cell line compared to on other cancer cell lines. All the compounds showed relative non-toxicity against normal cell line. The selectivity of the compounds against K562 cell line has been substantiated by molecular docking in BCR-ABL Tyrosine kinase using genetic algorithm program (GOLD 3.0.1). These results indicate that the chromone based derivatives 6a-6j and 8a-8e are promising anti-cancer agents for the effective treatment of different types of cancers. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A new series of pyrimidine based chromone hybrids were synthesized and evaluated for their anti-cancer activity, showing potent effects against A549, HeLa, and K562 cancer cell lines while maintaining relative non-toxicity against normal cell lines. The selectivity of these compounds against K562 cell line was confirmed using molecular docking analysis.