Recent advances in the synthesis and biological evaluation of hybrid compounds. Mini‐review: An account

Abstract The presence of N ‐heterocycles in many biologically active compounds has constituted a continuous stimulus for development in bio(organic) chemistry. Among the various N ‐heterocyclic scaffolds, triazoles form an important class of compounds with their abundant spectrum of therapeutic potential. Triazoles are useful linkers for hybridization with other bioactive moieties. This review highlights our recent achievements in the synthesis of triazole‐based hybrid compounds based on the copper(I)‐catalyzed azide alkyne Huisgen cycloaddtion reaction (CuAAC). More than 150 triazole‐based hybrid compounds (ester‐ and amide‐triazole linked‐triterpenoid‐AZT, ester‐ and amide‐triazole linked‐betulin‐AZT, triazole‐artesunate, triazole‐artemisinin, triazole‐indenoisoquinoline, triazole‐4‐anilinoquinazoline, and triazole‐chitin) were successfully synthesized. Moreover, the hybridization of triterpenoids with nucleosides HIV reserve‐transcriptase inhibitors (AZT, 3TC, d4T), 2‐aminobenzene derivatives, hydroxamic acids or hydroxamates using ester‐ or amide linkages were also reviewed. The biological evaluation of 250 hybrid compounds for the discovery of drug molecules has been discussed. Representative hybrid compounds exhibited remarkable anticancer activities with IC 50 < 1 µM and potent antiacetylchlorinesterase activity with IC 50 < 2 µM. Several ester‐linked conjugates of triterpenoid acids with AZT or 3TC displayed potent anti‐HIV activity with EC 50 values of 0.01 to 0.017 µM. These findings may impart new direction to medicinal and biochemists for further investigations of hybrid compounds containing anticancer, antibacterial agents, AChE, as well as anti‐HIV inhibitors.