SYNTHESIS & BIOLOGICAL EVALUATION OF SOME 2-SUBSTITUTED AMINO- BENZOTHIAZOLE DERIVATIVES AS AN ANTI-INFLAMMATORY AGENT

*Yogeshwari Madhukar Gaikwad, Vaishnavi Chhagan Kardile, Dr. Pratap Y. Pawar (M pharm Phd)

ABSTRACT

The pressing need for safer anti-inflammatory compounds has motivated us to investigate benzothiazole-derived molecules as promising candidates for replacing the conventional NSAIDs. Five novel 2-substituted aminobenzothiazoles (YG-1 to YG-5) were rationally designed and synthesized in a systematic three-step process with yields ranging from 46-77%. The compounds were fully characterized by FTIR and ¹H-NMR spectroscopy to validate their integrity. Molecular docking tests against cyclooxygenase-2 (COX-2) indicated favorable binding affinities between -7.632 and -8.412 kcal/mol, with the most active compound being YG-3. Interestingly, the compounds also satisfied Lipinski's Rule of Five, a drug-likeness requirement for potential oral drug delivery. In vivo anti-inflammatory activity in carrageenan- induced paw edema test led to identification of YG-1 as the most active compound, 80% edema inhibition at 100 mg/kg—equally effective as diclofenac sodium. Structure-activity relationship studies demonstrated that dual nitro substitution patterns significantly influence enhancing biological activity. These findings position 2-substituted aminobenzothiazoles as a valid lead structure for the identification of novel anti-inflammatory therapies. YG-1 is a lead worthy of further preclinical optimization, which could possess better safety profiles than existing NSAIDs without loss of therapeutic potency.

Keywords: Benzothiazole, Virtual Screening, Organic Synthesis, ADMET, NSAID.