CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
National Brain Research Centre, NH-8, Manesar, Gurgaon, Haryana, 122051, India.
Eur J Med Chem. 2017 Jul 28;135:89-109. doi: 10.1016/j.ejmech.2017.04.015. Epub 2017 Apr 13.
Nitrosporeusines A and B are two recently isolated marine natural products with novel skeleton and exceptional biological profile. Interesting antiviral activity of nitrosporeusines and promising potential in curing various diseases, evident from positive data from various animal models, led us to investigate their anti-inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines A and B in racemic as well as enantiopure forms. The natural product synthesis was followed by preparation of several analogues, and all the synthesized compounds were evaluated for in vitro and in vivo anti-inflammatory potential. Among them, compounds 25, 29 and 40 significantly reduced levels of nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines. In addition, these compounds suppressed several pro-inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), and thereby can be emerged as potent anti-inflammatory compounds. Furthermore, all possible isomers of lead compound 25 were synthesized, characterized and profiled in same set of assays and found that one of the enantiomer (-)-25a was superior among them.
硝孢菌素 A 和 B 是两种最近分离得到的海洋天然产物，具有新颖的骨架和优异的生物学特性。硝孢菌素具有有趣的抗病毒活性，并且在治疗各种疾病方面具有很大的潜力，从各种动物模型的积极数据中可以明显看出，这促使我们研究其抗炎潜力。因此，我们计划并以外消旋和对映纯形式合成硝孢菌素 A 和 B。在进行天然产物合成之后，我们还制备了几种类似物，并评估了所有合成化合物的体外和体内抗炎潜力。其中，化合物 25、29 和 40 显著降低了一氧化氮（NO）、活性氧（ROS）和促炎细胞因子的水平。此外，这些化合物还抑制了几种促炎介质，包括诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、核因子-κB（NF-κB），因此它们可能成为有效的抗炎化合物。此外，我们还合成、表征了先导化合物 25 的所有可能的异构体，并在同一组实验中进行了分析，结果发现其中一种对映异构体（-）-25a 是其中最优秀的。
