Chromones: Privileged scaffold in anticancer drug discovery

Abstract

In the design and discovery of anticancer drugs, various natural heterocyclic scaffolds have attracted considerable interest as privileged structures. For rational drug design, some of the natural scaffolds such as chromones have exhibited wide acceptability due to their drug-like properties. Among the approved anticancer drugs, the scaffolds with high selectivity for a small group of closely related targets are of importance. In the development of selective anticancer agents, the natural, as well as synthetic, can generate highly selective compounds toward cancer targets. The present manuscript includes more particularly the development of cancer inhibitors incorporating the chromone scaffold, with a strong emphasis on their molecular interactions in the anticancer mechanism. It also includes the structure-activity relationship studies and related examples of lead optimization.

Recent advances in transition metal-free annulation toward heterocycle diversity based on the C–N bond cleavage of enaminone platform

“…As a typical O -heterocyclic scaffold, the chromone skeleton is a well-documented core structure of numerous natural products 13 and bioactive lead compounds. 14 At present, chromone derivatives are normally synthesized via late-stage functionalization in the chromone backbone 15 or the chromone ring formation of acyclic building blocks. 1 b ,16 Among these known synthetic methods, the annulation of N , N -disubstituted 2-hydroxyphenyl enaminones based on a key C–N bond cleavage of enamines has been widely used in the construction of diversely functionalized chromones, especially the preparation of 3-substituted chromones.…”

Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment

“…[28][29][30] Mechanistically, tetrahydroisoquinolines, coumarins, and flavonoids could inhibit various enzymes like aromatase, carbonic anhydrase, kinase, telomerase, and sulfatase, so these derivatives could exert the anticancer activity via diverse mechanisms such as inhibiting angiogenesis, triggering cell cycle arrest and inducing apoptosis. [31][32][33] Hence, tetrahydroisoquinolines, coumarins, and flavonoids demonstrated broad-spectrum activity against both drug-susceptible and multidrug-resistant cancers, and hybridization of 1,2,3-triazole with tetrahydroisoquinoline/coumarin/flavonoid represents a promising strategy to develop novel antileukemic candidates with multiple action mechanisms.…”

Quantitative and Qualitative Analysis of the Anti-Proliferative Potential of the Pyrazole Scaffold in the Design of Anticancer Agents

“…The status of anticancer privileged heterocyclic scaffolds is not reserved for only nitrogen-based rings. Chromone [ 13 ] and coumarin [ 14 ] are examples of non-nitrogen structures that proved to be a useful template for the design of selective anticancer agents.…”