Abstract

Background: In the field of pharmaceutical chemistry, the anti-cancer activity of such compounds received great attention. For both medicinal and industrial studies. Xanthene derivatives are important class of compounds that have had many applications and this enhanced their uses in recent years. Xanthene and its derivatives are extensively used scaffolds in drug designing and the development of novel anti-cancer agents due to their large pharmaceutical applications.

Objective: The 3,3-dimethyl-2,3-dihydro-1H-xanthen-1-one was used to synthesise anti-cancer agents of fused pyran, pyridine, pyridazine, and thiophene derivatives. As the potentially privileged scaffolds, xanthene-fused bicyclic heterocycles may be used to discover new drugs with similar biological targets and improved therapeutic efficacy.

Methods: The key starting compound the 3,3-dimethyl-2,3-dihydro-1H-xanthen-1-one that was used in many heterocyclization reactions through its reactions with different reagents like aryldiazonium salts, reaction with S8 and producing fused tetracyclic compounds.

Results: Through this work, new compounds were synthesized, characterized, and evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The inhibitions on tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR for selected compounds were studied and the results were supplied by studying the mechanism of action toward EGFR. Furthermore, the morphological changes of selected cell lines by the effect of compounds 6b and 13c were studied.

Conclusion: We focused our attention on the synthesis of heterocyclic compounds based on xanthene moiety. After a detailed optimization study, many of the synthesized compounds can be considered anticancer agents, enhancing further studies.

Keywords: Dimedone, xanthenes, multicomponent, cytotoxicity, morphological studies, anti-cancer agents.