Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400 098, India.
J Mol Model. 2012 Apr;18(4):1481-93. doi: 10.1007/s00894-011-1177-2. Epub 2011 Jul 23.
The availability of the crystal structure of falcipain-3, knowledge of the peptides carrying the 7-aminocoumarin moiety as falcipain-3 ligands/substrates, and a need for new antimalarial agents stimulated us to look at the possibility of finding some novel falcipain-3 inhibitors. In this paper, we report the effect of substitution at the 7-amino position of the coumarin nucleus on the inhibition of falcipain-3, which is a well-validated antimalarial target. The de novo drug design was assisted by QSAR studies that shed light on the binding patterns of known and the newly designed inhibitors, thus taking this discovery process to the next level.
疟原虫蛋白酶 3 的晶体结构已经明确，带有 7-氨基香豆素部分的肽作为疟原虫蛋白酶 3 的配体/底物的知识，以及对新型抗疟药物的需求，这一切都激发了我们寻找新型疟原虫蛋白酶 3 抑制剂的可能性。在本文中，我们报告了香豆素核 7-氨基取代对抑制疟原虫蛋白酶 3 的影响，疟原虫蛋白酶 3 是一个经过充分验证的抗疟靶点。通过定量构效关系研究辅助的从头药物设计，揭示了已知和新设计抑制剂的结合模式，从而将这一发现过程提升到了一个新的水平。
