title: An approach to QSAR of 16-substituted pregnenolones as microsomal enzyme inducers.
abstract: In this study, we attempt to correlate quantitatively the structure of eight 16-substituted pregnenolones with microsomal enzyme inducing activity. We also performed some electrostatic potential calculations to get further insight into the properties of these substituents. It was found that pregnenolone-16 alpha-carbonitrile is the most active steroidal inducer among the pregnenolone derivatives tested. The receptor-inducer interaction is facilitated by a favourable electronic effect of the 16 alpha-substituents. The orientation of the electronegative area at position 16 seems to influence activity. Lipophilic and volume effects of the 16 alpha-substituents do not seem to be important for microsomal enzyme induction. However, substituent length has some influence on drug metabolising enzyme activity, probably interfering with receptor-inducer interactions.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece.
authors.forename: E A
authors.initials: EA
authors.lastname: Rekka
authors.forename: P N
authors.initials: PN
authors.lastname: Kourounakis
mesh_terms: D000818:Animals; D004790:Enzyme Induction; D005260:Female; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D011285:Pregnenolone Carbonitrile / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D011285:Pregnenolone Carbonitrile