A Convenient One-Pot Synthesis of Novel Benzimidazole–Thiazinone Derivatives and Their Antimicrobial Activity

<b>Background:</b> The increasing prevalence of antimicrobial resistant highlights the urgent need for the new therapeutic agents. This study aimed to design and synthesize fused tricyclic benzimidazole–thiazinone derivatives (<b>CS1</b>–<b>CS10</b>) through a con...

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Main Authors: Sabahat Samreen, Asghar Ali, Saiema Ahmedi, Mohammad Raghib, Anzarul Haque, Nikhat Manzoor, Afzal Hussain, Mohammad Abid, Afreen Inam
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/13/12/1155
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Summary:<b>Background:</b> The increasing prevalence of antimicrobial resistant highlights the urgent need for the new therapeutic agents. This study aimed to design and synthesize fused tricyclic benzimidazole–thiazinone derivatives (<b>CS1</b>–<b>CS10</b>) through a convenient method and evaluate their antimicrobial activity against various microorganisms. <b>Methods:</b> A series of fused tricyclic benzimidazole–thiazinone derivatives was rationally designed and synthesized in one pot by the reaction between trans substituted acrylic acids and 1<i>H</i>-benzo[d]imidazole-2-thiol using coupling reagent TBTU (2-(1<i>H</i>-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate). The structure of these compounds was confirmed through various spectroscopic techniques like IR, <sup>1</sup>H and <sup>13</sup>C NMR, the DEPT and 2D-HMQC NMR techniques were also performed to confirm the relation of both carbon and proton. Further, the compounds were in vitro evaluated for their effectiveness against the <i>Candida</i> species and a panel of standard bacterial isolates. <b>Results:</b> The synthesized compounds showed moderate antimicrobial activity. Among all of the compounds, <b>CS4</b> exhibited potent inhibition against <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i> at 256 and 512 μg/mL concentrations, respectively. Additional research indicated that compound <b>CS4</b> demonstrated a synergistic effect after combining with the standard antibacterial drug ciprofloxacin. <b>Conclusions:</b> These results suggest that <b>CS4</b> is the best-synthesized antibacterial agent particularly in combination therapies. These findings highlight its promise for further development as a novel antibacterial agent.
ISSN:2079-6382