3-(1-Phenyl-4-((2-(4-arylthiazol-2-yl)hydrazono)-methyl)-1H-pyrazol-3-yl)-2H-chromen-2-ones: one-pot three component condensation, in vitro antimicrobial, antioxidant and molecular docking studies

In an attempt to find a new class of heterocyclic bio-active agents, a series of novel 3-(1-phenyl-4-((2-(4-arylthiazol-2-yl)hydrazono)methyl)-1H-pyrazol-3-yl)-2H-chromen-2-one derivatives (5a-l) have been synthesized efficiently both quantitatively and qualitatively via a three-component one-pot manner by Hantzsch condensation. Structures of all the newly synthesized compounds were established by their spectral data and elemental analyses, and they were evaluated for their in vitro antimicrobial and antioxidant activities. Among the tested compounds (5a-l), the derivatives 5k, 5h and 5a have displayed broad spectrum antibacterial activity, whereas the compounds 5b and 5f were found to be potent antifungal agents. Antioxidant activity results revealed that compounds 5a, 5b and 5i exhibited higher radical scavenging ability than the positive control drug Trolax. Further, molecular docking of synthesized compounds (5a-l) into the binding site of the crystal structure of E. coli MurB enzyme (PDB Id: 1MBT), a key enzyme in peptidoglycan biosynthesis, was performed to gain a comprehensive understanding of the plausible binding modes and also to compare the theoretical and experimental results of these compounds. Docking results revealed that the docking scores and H-bonding interactions of the ligands are in good agreement with the in vitro results and also indicated that compounds 5k, 5h and 5a have considerable binding energies and greater affinity towards the active site of MurB enzyme. Thus, they can be further optimized and developed as lead compounds.