Synthesis and biological testing of new mimics or derivatives of selected cytotoxic lactones, antitumor agent tiazofurin and natural naphthenic acids

The aim of the first part of the project is development of new divergent synthesis of cytotoxic styryl lactones of type goniofufurone, crassalactones B-D and a series of new analogs having changed C-7 functions and/or furanofuranone core. De novo synthesis of new mimetics of the antitumor agent tiazofurin with modified sugar moieties is further planned. A study of structure-activity relationships (SAR) also represents an important task of the project. In vitro antiproliferative activities will be evaluated by using MTT assay, flow cytometry and Western blot analysis. The new analogs are expected to show better pharmacological effects that could serve as a basis for the development of new, slective anticancer drugs. The second part of the project focuses on the chemical and biological studies of natural petroleum (naphthenic) acids and its derivatives. It is planned to develop procedures for the synthesis of amides, in a microwave reactor without solvent, and for reduction of petroleum acids to the corresponding alcohols, using microwave catalysis. Studies of effect of petroleum acids and derivatives on certain physiological processes in plants (uptake of ions of essential elements, antioxidant status etc), as well as in vitro studies of bactericidal, fungicidal, antiviral and antitumor activity were also planned. The expected favorable biological effects could enable the development of novel products with potential practical application to agronomy and pharmacy.