Synthesis, in silico and Pharmacological Activity of 1, 3-Benzothiazol Derivatives

Background: Benzothiazole and its derivatives serve as a unique and versatile moiety for experimental drug design, especially in pharmaceutical chemistry, because of their potent pharmacological activities. Hence, the present study is planned to develop benzothiazole-containing benzohydrazide derivatives to determine what modifications result in a better corrective benzothiazole shift moiety that permits the achievement of a novel pharmacological profile, action and toxicity reduction. Materials and Methods: Five novel derivatives of benzothiazole containing benzohydrazide were synthesized and evaluated for their anti-inflammatory and analgesic activities through in silico and in vivo studies. Results: The molecular docking analysis displayed a strong binding affinity of the newly synthesized compounds with the receptors (PDB ID: 1EQG and 1CX2), with compound 3C exhibiting the highest binding energy of -10.41 and -9.20 kcal/mol. Compounds 3C and 3E prevented rat paw oedema caused by carrageenan at 70.03% and 62. 06%, at 1 hr, 74.38% and 71.04% at 2 hr and 78.11% and 76.14% at 3 hr, correspondingly. Throughout the study evaluating analgesic activity, components 3C, 3E and also 3B had ED50 (mM/kg) of 85 +/- 4.2 (Mean +/- SEM; n=4), 126 +/- 0.5, 95 +/- 1.6 after 0.5 hr; 71 +/- 4.8, 83 +/- 1.0 and 99 +/- 1.4, after 1 hr and 68 +/- 6.4, 75 +/- 5.7 and 87 +/- 2.1 mM/kg subsequent 2 hr, accordingly, it is comparably equated with 155 +/- 4.2, 70 +/- 1.4 and 69 +/- 0.9 mM/kg for celecoxib. Discussion: The Structure-Activity Relationship (SAR) analysis highlighted whether the replacement in the ortho/para position of benzohydrazide, despite furtherance of being part of halogen groups (I-2) and electron-rich -NH or -OH groups, played a crucial role in enhancing the anti-inflammatory and analgesic properties of the synthesized compounds. Conclusion: These findings underscore the potential of these derivatives as promising candidates for further development in the field of drug discovery.