Shankar Das Bhabani, Sarangi Ashirbad, Pahuja Isha, Singh Vishal, Ojha Suvendu, Giri Sidhartha, Bhaskar Ashima, Bhattacharya Debapriya
Center for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India.
Immunobiology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Cell Biochem Funct. 2024 Dec;42(8):e70030. doi: 10.1002/cbf.70030.
Tuberculosis (TB) remains a significant global health challenge, exacerbated by the emergence of drug-resistant strains of Mycobacterium tuberculosis (M. tb). The complex biology of M. tb, particularly its key porins, contributes to its resilience against conventional treatments, highlighting the exploration of innovative therapeutic strategies. Following with this challenges, the present study investigates the bioactivity properties of phenolic compounds derived from the terpene groups, specifically through Thymol (THY) against M. smegmatis as a surrogated model for M. tb. Furthermore, the study employed with combination of two approaches i.e., in vitro assays and computational methods to evaluate the efficacy of THY against M. smegmatis and its interaction with M. tb biofilm and efflux pump proteins, particularly Rv1258c and Rv0194. The in vitro findings demonstrated that THY exhibits inhibitory activity against M. smegmatis and shows promising interaction with a combination of isoniazid (INH) and rifampicin (RIF) of TB regimens. Furthermore, THY demonstrated significant inhibitory action towards motility and biofilm formation of M. smegmatis. The combination of THY with INH and RIF exhibited a synergistic effect, enhancing the overall antimicrobial efficacy. Additionally, THY displayed reactive oxygen species (ROS) activity and potential efflux pump inhibitory action towards M. smegmatis. The computational analysis revealed that THY interacts effectively with efflux pump proteins Rv1258c and Rv0194, showing superior binding affinity compared to verapamil, a known efflux pump inhibitor. Pharmacokinetic studies highlighted that THY possess a favourable safety profile. In conclusion, THY represents a promising inhibitory compound for tuberculosis prevention, potentially addressing challenges posed by drug resistance.
结核病（TB）仍然是一项重大的全球卫生挑战，而结核分枝杆菌（M. tb）耐药菌株的出现使其进一步恶化。M. tb复杂的生物学特性，尤其是其关键孔蛋白，使其对传统治疗具有抗性，这凸显了探索创新治疗策略的必要性。针对这些挑战，本研究调查了萜烯类酚类化合物的生物活性特性，特别是通过百里酚（THY）对耻垢分枝杆菌（M. smegmatis）进行研究，以此作为M. tb的替代模型。此外，该研究采用了两种方法相结合，即体外试验和计算方法，来评估THY对耻垢分枝杆菌的疗效及其与M. tb生物膜和外排泵蛋白（特别是Rv1258c和Rv0194）的相互作用。体外研究结果表明，THY对耻垢分枝杆菌具有抑制活性，并显示出与结核病治疗方案中的异烟肼（INH）和利福平（RIF）联合使用时具有良好的相互作用。此外，THY对耻垢分枝杆菌的运动性和生物膜形成具有显著的抑制作用。THY与INH和RIF联合使用表现出协同效应，增强了整体抗菌效果。此外，THY对耻垢分枝杆菌具有活性氧（ROS）活性和潜在的外排泵抑制作用。计算分析表明，THY与外排泵蛋白Rv1258c和Rv0194有效相互作用，与已知的外排泵抑制剂维拉帕米相比，显示出更高的结合亲和力。药代动力学研究强调，THY具有良好的安全性。总之，THY是一种有前景的结核病预防抑制化合物，有可能应对耐药性带来的挑战。
