title: Hansch analysis of antimalarial cyclic peroxy ketals with physicochemical and electrotopological parameters.
abstract: Hansch analysis of some antimalarial cyclic peroxy ketals (IV) having structural variations at the para substituted phenyl ring and an alicyclic ring of different size reveals that electronic and steric parameters of the phenyl ring substituents are important for explaining the variation in the activity while hydrophobicity parameter is of little significance. Electron withdrawing substituents with higher MR (molar refractivity) or V(W) (van der Waals volume) are preferred for the activity. Use of structural descriptors suggests that presence of a seven membered alicyclic ring attached to the peroxy bridge containing ring is conducive to the activity. Application of electrotopological state atom index (ETSAI) suggests a pharmacophore containing the peroxy bridge. This is corroborated by earlier observation on importance of oxygen atoms of the peroxy linkage of artemisinin for antimalarial activity. Although incorporation of ETSAI into Hansch model does not improve the relations, the electronic parameter sigma is found to be significantly correlated with it.
authors.affiliation: Division of Pharmaceutical Chemistry, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Orissa, India.
authors.forename: K
authors.initials: K
authors.lastname: Roy
authors.forename: D K
authors.initials: DK
authors.lastname: Pal
authors.forename: C
authors.initials: C
authors.lastname: Sengupta
mesh_terms: D000465:Algorithms; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015195:Drug Design; D004563:Electrochemistry; D010545:Peroxides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D001952:Bridged-Ring Compounds; D010545:Peroxides