title: Inhibition of classical pathway of complement activation with negative charged derivatives of bisphenol A and bisphenol disulphates.
abstract: In order to obtain strong inhibitors of classical pathway of complement activation the low weight negative charged compounds have been investigated. On the basis of bisphenol A anionic derivatives with one or two carboxylic, sulphate and phosphate groups the critical role of negative charged groups for complement-inhibiting activity has been established. It was determined that two sulphate or phosphate groups in the molecule provide the most inhibiting effect. At the next stage a set of bisphenol disulphates of varying structures has been synthesized and investigated. Bulky hydrophobic groups (cyclohexyliden, fluorenyliden, anthronyliden) at the central part of the bisphenol molecule it was found to increase complement-inhibiting activity markedly. The replacement of the ortho-positions to the charged group by halogens or alkyl groups (allyl, propyl) increases the inhibiting effect. It was showed by ELISA that several compounds studied interact with C1q, C1r /C1s components of complement. For the set of bisphenol disulphates the QSAR equation with hydrophobic coefficient and electronic parameters has been formulated. Both hydrophobic and electrostatic interactions it was established to have a great significance for the inhibition of classical pathway of complement activation.
authors.affiliation: Lomonosov Moscow Academy of Fine Chemical Technology, Department of Biotechnology, Pr. Vernadskogo, 86, 119571 Moscow, Russia. sveta407@mail.ru
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bureeva
authors.forename: Julian
authors.initials: J
authors.lastname: Andia-Pravdivy
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Petrov
authors.forename: Michael
authors.initials: M
authors.lastname: Igumnov
authors.forename: Sergey
authors.initials: S
authors.lastname: Romanov
authors.forename: Elena
authors.initials: E
authors.lastname: Kolesnikova
authors.forename: Alexander
authors.initials: A
authors.lastname: Kaplun
authors.forename: Leonid
authors.initials: L
authors.lastname: Kozlov
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D003167:Complement Activation; D004220:Disulfides / Q000737:chemistry*; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004220:Disulfides; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds