Lavekar Aditya G, Thakare Ritesh, Equbal Danish, Chopra Sidharth, Sinha Arun K
Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
Drug Dev Res. 2024 Feb;85(1):e22123. doi: 10.1002/ddr.22123. Epub 2023 Oct 15.
Sulfur-containing classes of the scaffold "Arylthioindoles" have been evaluated for antibacterial activity; they demonstrated excellent potency against methicillin-resistant Staphylococcus aureus (MRSA) as well as against vancomycin-resistant strains and a panel of clinical isolates of resistant strains. In this study, we have elucidated the mechanism of action of lead compounds, wherein they target the cell wall of S. aureus. Further, S. aureus failed to develop resistance against two lead compounds tested in a serial passage experiment in the presence of the compounds over a period of 40 days. Both the compounds demonstrated comparable in vivo efficacy with vancomycin in a neutropenic mice thigh infection model. The results of these antibacterial activities emphasize the excellent potential of thioethers for developing novel antibiotics and may fill in as a target for the adjustment of accessible molecules to develop new powerful antibacterial agents with fewer side effects.
对“芳硫基吲哚”支架结构的含硫类化合物进行了抗菌活性评估；它们对耐甲氧西林金黄色葡萄球菌（MRSA）、耐万古霉素菌株以及一组耐药菌株的临床分离株显示出优异的抗菌效力。在本研究中，我们阐明了先导化合物的作用机制，即它们靶向金黄色葡萄球菌的细胞壁。此外，在连续传代实验中，金黄色葡萄球菌在40天内接触两种受试先导化合物时未能产生耐药性。在中性粒细胞减少小鼠大腿感染模型中，这两种化合物在体内均显示出与万古霉素相当的疗效。这些抗菌活性结果强调了硫醚在开发新型抗生素方面的巨大潜力，并且可能成为调整现有分子以开发副作用更少的新型强效抗菌剂的靶点。
