title: Conformational analysis of rhazinilam and three-dimensional quantitative structure-activity relationships of rhazinilam analogues.
abstract: 3D QSAR of rhazinilam (1), an alkaloid isolated from Rhazya stricta (Apocynaceae) with an activity involving disassembly of microtubules and its derivatives was investigated by using the comparative molecular field analysis (CoMFA). In an effort to get a better understanding of the correlation between conformation and antitubulin activity of 1, most probable minimum energy conformation in solution of 1 was analyzed on the basis of NMR data of 1 in solution. The results indicated a correlation between the antitubulin activity of these alkaloids and the steric and electrostatic factors, which modulate their biological activity, and accounted for the potent activities of 1 with suitable relationship for the overall conformation.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.forename: A Hamid A
authors.initials: AH
authors.lastname: Hadi
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeya
authors.forename: Hideji
authors.initials: H
authors.lastname: Itokawa
authors.forename: Jun'ichi
authors.initials: J
authors.lastname: Kobayashi
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007212:Indolizines / Q000737:chemistry* / Q000494:pharmacology; D007769:Lactams / Q000737:chemistry* / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D014404:Tubulin / Q000187:drug effects
chemical_list: D000470:Alkaloids; D007212:Indolizines; D007769:Lactams; D014404:Tubulin; C009170:rhazinilam