SYNTHESIS AND IN VITRO CYTOTOXIC AND ANTIVIRAL ACTIVITIES OF 1-(2,5,6-TRIDEOXY-6-HALOGENOHEPT-5-ENOFURANURONONITRILE)THYMINE AND DERIVATIVES

ABSTRACT

All 1-(2,5,6-trideoxy-6-halogenohept-5-enofuranurononitrile)thymine and their 3′-O-TBDMS derivatives have been prepared and their configuration established. Some of these compounds are endowed with a cytotoxic or cytostatic activity in cell culture. The single most important factor affecting the cytotoxicity of these compounds is the presence on the molecule of a soft (electrofugal) halogen atom.

ACKNOWLEDGMENTS

The authors thank Dr Eder for the elemental analyses and Prof. F. Gulaçar for the mass spectra. The excellent technical asistance in the virological experiments by Mrs. Ann Absillis, Mrs. Frieda De Meyer, Mrs. Anita Camps, Mrs. Lies Vandenheurck and Mrs. Anita van Lierde and in the antiproliferative experiments by Mrs Céline Joulin and Mr Pascal Aumond was highly appreciated. This work was generally supported by the Swiss National Research Foundation (grant # 20.50827-97), by the European Commission, by FORTIS/ISEP, and by the Geconcerteerde Onderzoeksacties Vlaanderen, Krediet Nr 00/12.