Exploiting the potential of aryl acetamide derived Zn(ii) complexes in medicinal chemistry: synthesis, structural analysis, assessment of biological profile and molecular docking studies

Abstract

In the medical arena, advancements in the rational design of metal-based therapeutic agents showcase increasingly significant research efforts towards the development of new compounds with fewer toxic side effects. In this context, our present manuscript explicitly encapsulates the design and synthesis of Zn(II) complexes derived from different aryl acetamides, as potential frontline enzyme inhibitors as well as antileishmanial and anticancer agents. The structures of the synthesized metal complexes were established on the basis of spectro-analytical data and, in the case of 4c, by single crystal X-ray diffraction analysis. The X-ray structure of the Zn(II) complex, dichlorido-bis[N-(4-methoxyphenyl)acetamide-O]–zinc(II), 4c, showed that the zinc atom and the chloride ligands lie on a mirror plane, with the acetamide ligands in general positions. The coordination geometry of the zinc atom was tetrahedral, with the N-(4-methoxyphenyl)acetamide ligands bound to zinc via the acetamide oxygen atoms. The designed coordination complexes were analysed for their enzyme inhibition potential, and anticancer and antileishmanial efficacy. Detailed kinetic studies for complex 4b, the most active carbonic anhydrase and alkaline phosphatase inhibitor, indicated competitive and uncompetitive modes of inhibition against carbonic anhydrase and tissue non-specific alkaline phosphatase, respectively. The bioactivity results and molecular docking analysis revealed that the synthesized coordination complexes (4a–c) have great potential as enzyme inhibitors, in addition to being anticancer and anti-parasitic drug candidates.