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Ab initio quantum chemical analysis of stereoelectronic properties may explain in vitro antileishmanial activity of some macrocyclic bisbenzylisoquinoline alkaloids
Author(s) -
Bhattacharjee Apurba K.
Publication year - 1999
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1999)75:6<995::aid-qua3>3.0.co;2-#
Subject(s) - chemistry , ab initio , lone pair , homo/lumo , computational chemistry , molecular orbital , stereochemistry , ring (chemistry) , ether , molecule , organic chemistry
Despite phenomenal progress made in the understanding of molecular biology of Leishmaniasis in the past few decades, no new therapeutic agent has come up for the treatment of the disease since the introduction of pentavalent antimonials almost half a century ago. Discovery of some macrocyclic bisbenzylisoquinolines from natural products has shown promising antileishmanial activity in recent years, but their mechanism of action is not known. The present theoretical investigation attempts to identify and assess the role of calculated stereoelectronic properties of five such bisbenzylisoquinolines toward their observed antileishmanial activity. The study is an ab initio quantum chemical (3‐21G*/4‐31G*‐HF) analysis on the molecular electronic structure of gyrocarpine, daphnandrine, obaberine, pheanthine, and malekulatine. The ability to form a hole or cavity at the macrocyclic ring, preference for specific orientation of lone‐pair electrons of the ether–oxygen atoms, the electrostatic potential profiles by these oxygen atoms, and similarity of the lowest unoccupied molecular orbital (LUMO) isosurface at the hole are found to be related to potent in vitro antileishmanial activity. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 75: 995–1002, 1999