Eugenol derivatives containing 1,2,3-triazole-chalcone hybrids for shikimate kinase inhibition

Abstract

Eugenol, a primary component of clove oil, is a compound of considerable interest in medicinal chemistry due to its demonstrated potential as an effective agent in various therapeutic applications. In this study, a series of eugenol derivatives were designed and synthesized based on the hybridization of eugenol with 1,2,3-triazole and chalcone moieties. Compound 5j and 5k were denoted as lead structures against Mycobacterium tuberculosis Shikimate Kinase (MtSK). Moreover, the docking studies indicated that both the eugenol and triazole fragments in compound 5j and 5k played a pivotal role in the inhibition activity of MtSK, owing to their binding interactions with Arg58, Pro118, and Arg136 residues. Furthermore, in silico drug-likeness prediction analysis suggested that the majority of the synthesized compounds exhibit good oral bioavailability based on their molecular properties and Lipinski’s Rule of Five predictions.