Medicinal chemistry of analogues of nucleobases and nucleosides

Novel methodologies developed in our group are directly applied in the synthesis of modified nucleobases, nucleosides and nucleotides for biological activity screening. At first, series of new derivatives with a high degree of diversity of structural types are prepared and tested. In the next stage, fine tuning of structures of active lead compounds is performed. The series of new modified derivatives are being systematically screened on in vitro biological activity. Cytostatic activity is studied by Dr. I. Votruba on several cell-lines of cancers and leukemia (HeLaS3, L1210, HL60 a CCRF-CEM) and antiviral activity (in particular HCV) is studied in Gilead Sciences, Inc. (Foster City, CA, U.S.A.).

Several major novel types of biologically active compounds have been discovered by this screening. 6-Aryl- and 6-hetarylpurine ribonucleosides, possess significant cytostatic activity in submicromolar concentrations. 6-Hetarylpurine ribonucleosides also exert high anti-HCV activity. 6-(Hydroxymethyl)- and 6-(fluoromethyl)purine nucleosides as well as bis(purin-6-yl)acetylenes and -diacetylenes are other new types of cytostatic compounds prepared in our group.