Design, synthesis, molecular dynamics and in silico pharmacokinetic study of N-(4-(thiazol-2-ylamino)phenyl)benzamide analogues as promising anti-inflammatory agentsManoj Kashyap, Muslek Uddin Mazumder, Pooja Patowary, Lalnun Hruaitluangi, Lalzikpuii Sailo, Babita Deka, Debaprotim Dasgupta, Apurba Talukdar, and Bhargab Jyoti Sahariah NETES Institute of Pharmaceutical Science, NEMCARE Group of Institutions, Kamrup, India
E-mail: kashyapmanoj181@gmail.com Received: 19 June 2025 Accepted: 18 November 2025 Abstract: Six N-(4-(thiazol-2-ylamino)phenyl)benzamide derivatives (MK1–MK6) were designed and synthesized as potential anti-inflammatory agents. Among them, N-(4-(benzo[d]thiazol-2-ylamino)phenyl)benzamide (MK2) exhibited the highest activity in the in vitro protein denaturation inhibition assay (98.99 µg/mL), comparable to diclofenac (91.32 µg/mL). In the in vivo carrageenan-induced rat paw edema model, MK2 produced a significant reduction in paw volume (p < 0.001) at both low and high doses, demonstrating potent anti-inflammatory efficacy. Acute toxicity evaluation confirmed its safety up to 550 mg/kg. In silico molecular docking and 100 ns dynamics simulation against cyclooxygenase-2 (PDB ID: 3PGH) showed strong and stable binding interactions, particularly for MK2. ADME and drug-likeness analysis indicated favorable pharmacokinetic properties, including high gastrointestinal absorption and compliance with Lipinski’s rule of five. Overall, compound MK2 emerged as the most promising lead with excellent biological performance across in vitro, in vivo, and in silico studies, supporting its potential as a safe and effective anti-inflammatory candidate. Graphical abstract Keywords: Thiazole; Benzamide; Cyclooxygenase; Docking; Carrageenan; Simulation Full paper is available at www.springerlink.com. DOI: 10.1007/s11696-025-04535-1
Chemical Papers 80 (3) 2627–2645 (2026) |
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