Pogaku Vinay, Krishna Vagolu Siva, Sriram Dharmarajan, Rangan Krishnan, Basavoju Srinivas
Department of Chemistry, National Institute of Technology, Warangal 506 004, Telangana, India.
Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
Bioorg Med Chem Lett. 2019 Jul 1;29(13):1682-1687. doi: 10.1016/j.bmcl.2019.04.026. Epub 2019 Apr 17.
The aim of the study is to design and synthesis of a new series of potent anti-TB 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines with their safety profile. A synergetic effect of ultrasonication and ionic liquid was shown successfully as a green methodology for the synthesis of title compounds 6a-t. These derivatives were obtained in shorter reaction time with good yields and well characterized by various spectroscopic methods, single-crystal X-ray diffraction (6f). The in vitro anti-tuberculosis activity for newly-synthesized derivatives has been screened against Mycobacterium tuberculosis. Among all, six compounds 6e, 6k, 6l, 6n, 6q and 6r exhibited equal potent activity compared to standard drug ethambutol (MIC: 1.56 µg/mL) and another compound 6h exhibited outstanding activity (MIC: 0.78 µg/mL) than the standard drug ethambutol. Cytotoxic nature of the anti-TB active compounds was evaluated against RAW 264.7 cells. The 6h, 6e, 6k, 6l, 6n, 6q and 6r exhibited lower toxicity which could be promising hits for anti-tuberculosis.
本研究的目的是设计并合成一系列新型的具有高效抗结核活性的基于1,2,4-三唑-1-基吡唑的螺环氧化吲哚吡咯烷类化合物，并研究其安全性。超声和离子液体的协同效应已成功地作为一种绿色方法用于合成标题化合物6a-t。这些衍生物在较短的反应时间内获得，产率良好，并通过各种光谱方法、单晶X射线衍射（6f）进行了充分表征。对新合成的衍生物进行了抗结核分枝杆菌的体外抗结核活性筛选。其中，六种化合物6e、6k、6l、6n、6q和6r与标准药物乙胺丁醇（MIC：1.56 µg/mL）表现出同等的强效活性，另一种化合物6h表现出比标准药物乙胺丁醇更优异的活性（MIC：0.78 µg/mL）。评估了抗结核活性化合物对RAW 264.7细胞的细胞毒性。6h、6e、6k、6l、6n、6q和6r表现出较低的毒性，可能是抗结核的有前景的候选物。
