1. A NEW CANDIDATE FOR THE L-NUCLEOSIDES RESERVOIR MALINA JASAMAI Department of Pharmacy, FSKB, UKM. malina@medic.ukm.my

3. Aims and Objectives

4. Overview  Nucleoside structure - Mechanism of action  Target compounds - Comparison between thio and oxo and rationale for thio synthesis - L -thionucleosides  Synthetic methodology  Antiviral assay

5. Introduction  Structure of nucleotide and nucleoside

6. Nucleoside analogues in clinical use

7. Mechanism of Action

9. Target Compounds

10. Thio vs Oxo Rationale of isostere substitution:  increased stability against nucleoside phosphorylase  reduced toxicity in vivo

14. Eureka!

15. Biological Evaluation Cell typesVirusesPeriod of incubation HEL cells HSV-1, HSV-2, Vaccinia virus, VZV and HSV TK - ACV - 3-4 days HeLa cells VSV, Coxakie B1 virus and RSV1-2 days Vero cells Simbis virus and Coxakie B1 virus Punta Toro virus, Reo virus and Parainfluenza virus 1-2 days 3-4 days CCRF-CEM cells HIV-1 and HIV-23-4 days MT-4 cells HIV-2 and HIV-23-4 days

16. Million of Thanks!  Malaysian Government for Phd funding  Dr Claire Simons for her supervision and assistance  Prof Jan Balzarini and staff at Rega Institute  My colleagues in Lab 2.22 and everyone in Medicinal Chemistry discipline