Synthesis and Biological Evaluation of 2‐Mercapto‐1,3‐benzothiazole Derivatives with Potential Antimicrobial Activity

Abstract

The enhancement of bacterial resistance of pathogens to currently available antibiotics constitutes a serious public health threat. So, intensive efforts are underway worldwide to develop new antimicrobial agents. To identify compounds with a potent antimicrobial profile, we designed and synthesized low molecular weight 2-mercaptobenzothiazole derivatives 2a-2l and 3a-3l. Both series were screened for in-vitro antibacterial activity against the representative panel of Gram-positive and Gram-negative bacteria strains. The biological screening identified compounds 2e and 2l as the most active ones showing an interesting antibacterial activity with MIC values of 3.12 microg/mL against Staphylococcus aureus and 25 microg/mL against Escherichia coli, respectively. The replacement of the S-H by the S-Bn moiety resulted in considerable loss of the antibacterial action of the 3a-3l series. The antibiotic action of compounds 2e and 2l was also investigated by testing their activity against some clinical isolates with different antimicrobial resistance profile. Moreover, the involvement of the NorA efflux pump in the antibacterial activity of our molecules was evaluated. Finally, in this paper, we also describe the cytotoxic activity of the most interesting compounds by MTS assay against HeLa and MRC-5 cell lines.

2-Aminobenzothiazole derivatives: Search for new antifungal agents

“…The results, expressed as MIC (mg/mL), are listed in Table 2. The antibacterial screening revealed that the compounds showed very low to no activity against all the bacterial strains tested, thus underlying that isosteric substitution SH/NH 2 brought to a loss of the antibacterial activity, as evidenced by comparing 1b,c,jel with their corresponding isosters previously reported [6].…”

“…Comparison of these compounds with the series of 2-mercapto-1,3-benzothiazole derivatives previously reported [6] showed that the isosteric substitution SH/NH 2 at position 2 brought to the loss of activity against bacteria but to the appearance of an interesting activity toward fungi strains. This result confirms our previous hypothesis that the SH moiety at the 2 position of the heterocyclic nucleus is crucial for antibacterial activity.…”

“…In fact, benzothiazole derivatives possess a wide spectrum of biological applications such as antitumor, schictosomicidal, anti-inflammatory, anticonvulsant, antidiabetic, antipsychotic, diuretic, and antimicrobial activities [5]. In the past, our research group was interested in the synthesis and microbiological screening of a series of 2-mercapto-1,3-benzothiazole derivatives, some of which showed antibacterial activity against Gram-positive and negative bacterial strains [6]. Results showed that the SH moiety at the 2 position of the heterocyclic nucleus led to a remarkable antibacterial activity.…”

“…It was reported, indeed, that several 2-aminobenzothiazole derivatives, variously substituted, showed antifungal activity, even though much lower than those of the reference antifungal agent used [8]. In particular, as it was already done for the series of 2-mercapto-1,3-benzothiazole derivatives [6], substitutions at position 6 of the aryl moiety was investigated. QSAR and docking studies gave valuable hints assessing lipophilicity and steric hindrance as main molecular determinants most likely affecting the newly synthesized benzothiazole derivatives in their antifungal activity.…”

Regioselective synthesis and biological evaluation of some novel thiophene-containing heterocyclic scaffolds as potential chemotherapeutic agents

“…Therefore, the development of new and efficacious antimicrobial drugs is a very important goal, and most of the research efforts in this field are directed towards the design of new agents. A review of the recent literature shows that many effective antimicrobial agents contain a heterocyclic moiety within their structure [4,5] with special emphasis on those agents incorporating a thiophene moiety [6][7][8][9][10]. The thiophene ring system is notably a structural component of the commercial imidazole antifungal agent sertaconazole [11].…”