In-silico based Designing of benzo[d]thiazol-2-amine Derivatives as Analgesic and Anti-inflammatory Agents


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Background:Benzo[d]thiazoles represent a significant class of heterocyclic com-pounds renowned for their diverse pharmacological activities, including analgesic and anti-inflammatory properties. This molecular scaffold holds substantial interest among medicinal chemists owing to its structural versatility and therapeutic potential. Incorporating the benzo[d]thiazole moiety into drug molecules has been extensively investigated as a strategy to craft novel therapeutics with heightened efficacy and minimized adverse effects.

Aims:The aim of the present research work was to design, synthesize and characterize the new benzo[d]thiazol-2-amine derivatives as potent analgesic and anti-inflammatory agents.

Materials and Methods:The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and Mass spectroscopy methods were used to characterize the structural properties of all 13 newly synthesized derivatives. The molecular properties of these newly synthesized derivatives were estimated to study the attributes of drug-like candidates. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2.

:Analgesic and anti-inflammatory activities of synthesized compounds were evaluated by using albino rats.

Results:Findings of the research suggested that compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8 and G10 showed lower binding affinity than Indometh-acin when docking was performed with enzyme COX-2. In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities was performed for synthesized compounds.

Discussion:Compounds G10 and G11 exhibited significant COX-1 and COX-2 enzyme in-hibitory action with an IC50 value of 5.0 and 10 µM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. Highest analgesic action was exhibited by derivative G11 and the compound G10 showed the highest anti-inflammatory response. Inhibition of COX may be considered as a mechanism of action of these compounds.

Conclusion:It was concluded that synthesized derivatives G10 and G11 exhibited significant analgesic and anti-inflammatory effect; therefore, the said compounds may be subjected to further clinical investigation for establishing these as future compounds for the treatment of pain and inflammation.

Sobre autores

Arun Mishra

Central Facility of Instrumentation, SOS School of Pharmacy, IFTM University

Autor responsável pela correspondência
Email: info@benthamscience.net

Kamal Thajudeen

Department of Pharmacognosy, College of Pharmacy, King Khalid University

Email: info@benthamscience.net

Mhaveer Singh

School of Pharmaceutical Sciences, IFTM University

Email: info@benthamscience.net

Gulam Rasool

Drug Design Laboratory, School of Pharmaceutical Sciences, IFTM University

Email: info@benthamscience.net

Arvind Kumar

Drug Design Laboratory, School of Pharmaceutical Sciences, IFTM University

Email: info@benthamscience.net

Harpreet Singh

Drug Design Laboratory, School of Pharmaceutical Sciences, IFTM University

Email: info@benthamscience.net

Kalicharan Sharma

School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research University

Email: info@benthamscience.net

Amrita Mishra

School of Pharmaceutical Sciences, Delhi Pharmaceutical Science and Research University

Email: info@benthamscience.net

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