Triazole and Pyrazole Hybrids of Electrophilic Natural Products as Promising Anticancer Agents

Naturally inspired electrophilic scaffolds, such as chalcone, curcumin, aurone, C-5-monocarbonyl-curcumin, and bis-(arylidene)piperidone, are considered privileged structures because of their ability to interact with a variety of biological macromolecules, including receptors and enzymes. They thus serve as versatile platforms for drug discovery efforts aimed at developing structurally related analogues endowed with improved bioactivity. Five-membered nitrogen-based heterocycles, such as triazole and pyrazole, have been widely used in medicinal chemistry both as templates and spacers for the design of bioactive compounds; they indeed provide the advantage of enhancing favourable interactions with the target, while also improving solubility and bioavailability, along with reducing toxicity. This review reports the latest advances in the development of hybrids incorporating the above classes of synthons acting as potential anticancer chemotherapeutics and provides a critical summary of the design strategies that have guided the development of antitumor agents.