Alniss Hasan Y, Siddiqui Ruqaiyyah, Daalah Meshal, Al-Jubeh Hadeel M, Msallam Yousef A, Alawfi Bader S, Sajeev Sreedevi, Ravi Anil, Khan Naveed A
College of Pharmacy, Department of Medicinal Chemistry, University of Sharjah 27272 Sharjah United Arab Emirates
Research Institute for Medical and Health Sciences, University of Sharjah 27272 Sharjah United Arab Emirates.
RSC Med Chem. 2025 Jul 31. doi: 10.1039/d5md00475f.
Due to limited advances in diagnosis and targeted therapy, as well as poor understanding of pathophysiology, infections due to have remained a medical concern. With their ability to selectively bind to DNA sequences, minor groove binders have emerged as useful therapeutic agents against parasitic infections. Herein, 6 novel thiazole-based minor groove binders were synthesized. Purification of intermediate compounds was accomplished by utilising silica gel column chromatography, while thin-layer chromatography was utilised to monitor reactions. The purification of the final products was achieved using liquid chromatography. Confirmation of structures was achieved by NMR spectroscopy and mass spectrometry. All compounds were evaluated against pathogenic assays. At micromolar concentrations, selected minor groove binder derivatives revealed potent effects against (i) trophozoites as observed using amoebicidal assays, (ii), against cysts as observed using excystation assays, and (iii) against -mediated host cell death utilising human cerebrovascular endothelial cells, but (iv) showed limited effects against host cells alone, using cytotoxicity assays. The binding interaction between minor groove binders and DNA was studied using isothermal titration calorimetry and molecular docking simulations to provide insights into their binding affinity and mode of interaction. The findings of our study underscore the therapeutic value of thiazole-based minor groove binders as potent agents against , demonstrating effective antiamoebic activity with a low propensity for human cell damage, thus supporting their further development as antiamoebic agents.
由于诊断和靶向治疗进展有限，以及对病理生理学的了解不足，[病原体名称]感染一直是医学关注的问题。由于能够选择性地与DNA序列结合，小沟结合剂已成为对抗寄生虫感染的有用治疗剂。在此，合成了6种新型噻唑基小沟结合剂。中间化合物的纯化通过硅胶柱色谱法完成，而薄层色谱法用于监测反应。最终产物的纯化使用液相色谱法实现。结构确认通过核磁共振光谱和质谱完成。所有化合物均针对致病性[病原体名称]进行了评估。在微摩尔浓度下，所选的小沟结合剂衍生物显示出对（i）滋养体有显著作用，如通过杀阿米巴试验观察到的；（ii）对包囊有作用，如通过脱囊试验观察到的；（iii）利用人脑血管内皮细胞对[病原体名称]介导的宿主细胞死亡有作用，但（iv）使用细胞毒性试验单独对宿主细胞的作用有限。使用等温滴定量热法和分子对接模拟研究了小沟结合剂与DNA之间的结合相互作用，以深入了解它们的结合亲和力和相互作用模式。我们的研究结果强调了噻唑基小沟结合剂作为对抗[病原体名称]的有效药物的治疗价值，证明了其具有有效的抗阿米巴活性且对人类细胞损伤倾向较低，从而支持将其进一步开发为抗阿米巴药物。
