New AZT Analogues Having 5′-Alkylsulfonyl Groups: Synthesis and Anti-HIV Activity

Abstract

New derivatives of azidothymidine (AZT) substituted by alkyl and alkylsulphonyl groups at N-3 and C-5′, respectively, have been synthesized. The new synthesized derivatives showed remarkable anti-HIV-1 and HIV-2 activity in MT-4 cells. Compounds 8 and 10 have IC₅₀ values of 0.83 and 0.31 μg/mL against HIV-1 with therapeutic index of 83 and 403, respectively, and IC₅₀ values of 0.93 and 0.29 μg/mL against HIV-2 with therapeutic index of 74 and 431, respectively. This means that compounds 8 and 10 were cytotoxic to MT-4 cells at CC₅₀ of 69.2 μg/mL and 125 μg/mL, respectively.

Keywords:

• Anti-HIV activity
• alkylsulfonyl group
• azidothymidine (AZT)
• N-nucleosides
• substitution reaction

Acknowledgments

We thank Miss Friemel of Chemistry Department, University of Konstanz, Germany, for the 2D NMR experiments.

Notes

^a Anti-HIV-1 activity measured with strain III_B.

^b Anti-HIV-2 activity measured with strain ROD.

^c Compound concentration required to achieve 50% protection of MT-4 cells from the HIV-1- and 2-induced cytopathogenic effect.

^d Compound concentration that reduces the viability of mock-infected MT-4 cells by 50%.

^e SI: Selectivity index (CC₅₀/IC₅₀).