Legac Jenny, Adeniyi Adebayo A, Kisten Prishani, Rosenthal Philip J, Singh Parvesh, Kumar Vipan
Department of Chemistry, Guru Nanak Dev University, Amritsar-143005, Punjab, India.
Department of Medicine, University of California, San Francisco, California 94115, United States.
ACS Med Chem Lett. 2020 Jan 8;11(2):154-161. doi: 10.1021/acsmedchemlett.9b00521. eCollection 2020 Feb 13.
A series of 25 conjugates has been synthesized to evaluate their antiplasmodial potency and cytotoxicity against the chloroquine resistant (CQR) W2 strain of and Vero kidney cell lines, respectively. Most of the compounds showed IC values in the lower nM range and proved to be many fold more active than chloroquine (CQ). The studies were extended to decipher modes of action using techniques including UV-vis absorption, NMR titrations, and mass spectrometry, and conclusions were strengthened by docking and density functional theory (DFT) simulations. The most active compound, with IC 15 nM and selectivity index >4000, proved to be an interesting template for antimalarial drug discovery. To the best of our knowledge this is the first report of a potent naphthalimide based antiplasmodial conjugate.
已合成了一系列25种共轭物，分别评估它们对氯喹抗性（CQR）W2疟原虫株和Vero肾细胞系的抗疟活性和细胞毒性。大多数化合物的IC值处于较低的纳摩尔范围，并且被证明比氯喹（CQ）活性高许多倍。研究通过紫外可见吸收、核磁共振滴定和质谱等技术扩展到破译作用模式，对接和密度泛函理论（DFT）模拟进一步强化了结论。活性最高的化合物，IC为15纳摩尔，选择性指数>4000，被证明是抗疟药物发现的一个有趣模板。据我们所知，这是第一篇关于基于萘二甲酰亚胺的强效抗疟共轭物的报道。
