Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach

Abstract

Abstract:A new series of N-(6-arylbenzo [d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

“…All compounds interacted better with site B than site A of H. pylori urease, indicating that these molecules participate in a stronger bond with site B than with site A. Furthermore, an inversely proportional linear correlation between the number of hydrogen bonds and the IC 50 was noted [77] .

Scheme 23 Chemical structures of urease inhibitors based on 6-aryl-2-acetamidobenzothiazoles.

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“…Conjugation of benzothiazole and acyl thiourea cores was also exploited by Gull et al [77] to obtain hybrid 6-aryl-2-acetamidobenzothiazoles ( Scheme 23 ). All compounds displayed similar range of inhibitory activity, with an IC 50 of approximately 18 µg/mL, and were more active than thiourea.…”

Design, synthesis, and biological evaluation of novel N4-substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors

“…The Lewis acid property of acetamides renders them useful as analytical reagents and in the preparation of a number of coordination complexes [24]. The acetamide functional group is responsible for antimicrobial [25, 26], antioxidant [27, 28], narcolepsy treatment [29], anti-inflammatory [30, 31], platelet aggregation inhibitory [32], and urease inhibitory activities [33]. The acetamides and their analogues are also well studied as chemotherapeutic agents [34, 35].…”

Recent investigations into synthesis and pharmacological activities of phenoxy acetamide and its derivatives (chalcone, indole and quinoline) as possible therapeutic candidates

“…The domain of drug research deals primarily with both the design and development of new drugs, based on an understanding as to how they function to target a particular gene at the molecular level [ 61 ]. Molecules with acetamide linkage and its derivatives as core structures are reported to exhibit a wide spectrum of biological activities [ 62 ]. Therefore, special attention has also been given to acetamide medications because of their possible use as a therapeutic agent.…”