A NEW CANDIDATE FOR THE L-NUCLEOSIDES RESERVOIR MALINA JASAMAI Department of Pharmacy, FSKB, UKM.

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Presentation transcript:

A NEW CANDIDATE FOR THE L-NUCLEOSIDES RESERVOIR MALINA JASAMAI Department of Pharmacy, FSKB, UKM.

Aims and Objectives

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

Introduction  Structure of nucleotide and nucleoside

Nucleoside analogues in clinical use

Mechanism of Action

Target Compounds

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

Eureka!

Biological Evaluation Cell typesVirusesPeriod of incubation HEL cells HSV-1, HSV-2, Vaccinia virus, VZV and HSV TK - ACV 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

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