Das Dipendu, Khan Hina P A, Shivahare Rahul, Gupta Suman, Sarkar Jayanta, Siddiqui Mohd Imran, Ampapathi Ravi Sankar, Chakraborty Tushar Kanti
Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Org Biomol Chem. 2017 Apr 11;15(15):3337-3352. doi: 10.1039/c6ob02610a.
Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, is one of the most neglected diseases endemic in many continents posing enormous global health threats and therefore the discovery of new antileishmanial compounds is of utmost urgency. The antileishmanial activities of a library of sugar amino acid-based linear lipopeptide analogues were examined with the aim to identify potential drug candidates to treat visceral leishmaniasis. It was found that among the synthesized analogues, most of the permethylated compounds exhibited more activity in in vitro studies against intra-macrophagic amastigotes than the non-methylated analogues. SAR and NMR studies revealed that introduction of the N-methyl groups inhibited the formation of any turn structure in these molecules, which led to their improved activities.
利什曼病由利什曼原虫属的原生动物寄生虫引起，是许多大陆流行的最被忽视的疾病之一，对全球健康构成巨大威胁，因此发现新的抗利什曼化合物迫在眉睫。研究了一组基于糖氨基酸的线性脂肽类似物库的抗利什曼活性，旨在确定治疗内脏利什曼病的潜在候选药物。结果发现，在合成的类似物中，大多数全甲基化化合物在体外对巨噬细胞内无鞭毛体的研究中表现出比未甲基化类似物更高的活性。构效关系和核磁共振研究表明，N-甲基基团的引入抑制了这些分子中任何转角结构的形成，从而提高了它们的活性。
