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

Abstract

Background: 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 (CS1-CS10) through a convenient method and evaluate their antimicrobial activity against various microorganisms. Methods: 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 1H-benzo[d]imidazole-2-thiol using coupling reagent TBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate). The structure of these compounds was confirmed through various spectroscopic techniques like IR, ¹H and ¹³C 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 Candida species and a panel of standard bacterial isolates. Results: The synthesized compounds showed moderate antimicrobial activity. Among all of the compounds, CS4 exhibited potent inhibition against Pseudomonas aeruginosa and Escherichia coli at 256 and 512 μg/mL concentrations, respectively. Additional research indicated that compound CS4 demonstrated a synergistic effect after combining with the standard antibacterial drug ciprofloxacin. Conclusions: These results suggest that CS4 is the best-synthesized antibacterial agent particularly in combination therapies. These findings highlight its promise for further development as a novel antibacterial agent.

Keywords: Candida species; TBTU; antibacterial; antifungal; synergetic effect; thiazinone.

Figure 1

Rational design of the proposed compound [23,24,25,26,27].

Scheme 1

Reagents and conditions: (a) TBTU, DIPEA, dry DMF, stirred at room temperature for 36 h.

Scheme 2

Proposed mechanism for the formation of benzimidazole–thiazinone derivatives.

Figure 2

¹H NMR spectrum of compound CS1, representing the aromatic region.

Figure 3

¹H NMR spectrum of compound CS1, representing the aliphatic region.