Complement C1q-target proteins recognition is inhibited by electric moment effectors.

Classical complement pathway is an important innate immune mechanism, which is usually triggered by binding of C1q to immunoglobulins, pentraxins and other target molecules. Although the activation of the classical pathway is crucial in the host defence, its undesirable and uncontrolled activation can lead to tissue damage. Thus, understanding the molecular basis of complement activation and its inhibition are of great biomedical importance.

Selective inhibition of the interaction of C1q with immunoglobulins and the classical pathway of complement activation by steroids and triterpenoids sulfates.

Since undesirable activation of the complement system through the classical pathway is associated with tissue damage and other pathologic proinflammatory consequences at ischemia/reperfusion injury, autoimmune diseases, and rejection of allo- and xenografts, creation of selective inhibitors of the classical pathway leaving the alternative pathway intact is of great importance. Classical pathway is triggered by binding of its recognizing unit, protein C1q, to a number of targets like antibodies, pentraxins, apoptotic cells, and others. In order to obtain inhibitors blocking the first step of the classical cascade, synthesis of sulfates of steroids (Delta(5)-3beta-hydroxycholenic, Delta(5)-3beta-hydroxyetiocholenic, deoxycholic, and cholic acids) and triterpenoids (betulin, 20,29-dihydro-20,29-dichloromethylenbetulin, betulinic, ursolic, and oleanolic acids) has been performed.

Drug design using the example of the complement system inhibitors' development.

Undesired activation of the complement system, a part of the immune system, is a major pathogenic factor contributing to various diseases, such as ischemia-reperfusion injury, sepsis, asthma, allergic reactions, rheumatoid arthritis, Alzheimer's disease, myasthenia, multiple sclerosis and others. The history of the development of complement system inhibitors, preventing its destructive action on the body, represents the evolution of the main methods of drug design. This review illustrates the main approaches of drug design, ranging from screening and modification of natural products to structure-based ligand design, on the basis of complement inhibitors' creation.

Inhibition of classical pathway of complement activation with negative charged derivatives of bisphenol A and bisphenol disulphates.

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.