Design, Synthesis, and Exploration of Biological Activities of Novel Benzoxazole Derivatives through In-silico and In...

Many natural and synthetic compounds have been investigated for their anti-inflammatory and analgesic properties, but most of them possess significant adverse effects. The versatility of benzoxazole derivatives allows for the design of compounds with specific target interactions. Structural modifications may lead to the development of more efficacious and safer drugs for various medical conditions.

A series of substituted benzoxazole compounds was synthesized, yielding six (E)-1-[4-{2- (benzo[d]oxazol-2-yl)phenylamino}phenyl]-3-(substituted phenyl)prop-2-en-1-ones, denoted as 3a-3f, and further characterized by IR, NMR, and mass spectroscopic methods. The synthesized derivatives were tested for anti-inflammatory and analgesic activities using animal models. The binding interactions of the synthetic compounds with the targets were investigated through a molecular docking study using Schrodinger Maestro version 2022-4. Molecular dynamics (MD) simulation was performed for 50 ns to investigate the protein's characteristics, monitor internal molecular transformations, and assess the long-term stability of the protein-ligand complex.

All the compounds exhibited significant anti-inflammatory and analgesic activities at a dose of 100 mg/kg compared to Diclofenac. In in silico studies, the compounds exhibited the required binding interactions and stability.

The docking studies indicated that the compound substituted with 3-hydroxyphenyl (3c) behaved as a COX-1 inhibitor. The simulated complexes of 3c with COX-1 and COX-2 demonstrated stability throughout the simulation, with RMSD values of 3.5 Å and 4 Å, respectively.

The present research would pave the way for researchers to synthesize more benzoxazole derivatives devoid of significant adverse effects using novel approaches.