1. Phosphoramidate conjugates of 3′-azido-3′-deoxythymidine glycerolipid derivatives and amino acid esters: synthesis and anti-HIV activity
- Author
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Andrei E. Siniavin, Elizaveta S. Darnotuk, N. S. Shastina, Nikolay V. Shulga, and Karamov Ev
- Subjects
chemistry.chemical_classification ,Anti hiv activity ,010405 organic chemistry ,Chemistry ,Stereochemistry ,viruses ,Organic Chemistry ,virus diseases ,Phosphoramidate ,biochemical phenomena, metabolism, and nutrition ,01 natural sciences ,0104 chemical sciences ,Amino acid ,010404 medicinal & biomolecular chemistry ,Bioorganic chemistry ,heterocyclic compounds ,General Pharmacology, Toxicology and Pharmaceutics ,3 azido 3 deoxythymidine ,Selectivity ,EC50 ,Conjugate - Abstract
We report the synthesis of phosphoramidate conjugates of 3′-azido-3′-deoxythymidine (AZT) glycerolipid derivatives and amino acid esters. For the synthesized compounds, 50% inhibition of the HIV-1 MvP-899 strain in human T lymphoid MT-4 cells is achieved at concentrations of 0.014–0.356 µM. Significantly, compound 3c (which contained ethyl ester of α-alanine) was found to be the most active with EC50 value 0.014 µM. We show that, among these glycerolipid derivatives of AZT, some compounds are less toxic than AZT, and also they possess a similar or higher selectivity index compared to AZT (SI = 11643).
- Published
- 2021
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