1. Design, synthesis and biological evaluation of substituted (+)-SG-1 derivatives as novel anti-HIV agents.
- Author
-
Liu X, Chen P, Li X, Ba M, Jiao X, Guo Y, and Xie P
- Subjects
- Anti-HIV Agents chemical synthesis, Anti-HIV Agents chemistry, Dose-Response Relationship, Drug, Drug Resistance, Viral drug effects, Gangliosides chemical synthesis, Gangliosides chemistry, Microbial Sensitivity Tests, Molecular Structure, Stereoisomerism, Structure-Activity Relationship, Anti-HIV Agents pharmacology, Gangliosides pharmacology, HIV-1 drug effects
- Abstract
SG-1 was previously identified as a potent Non-nucleoside reverse transcriptase inhibitors (NNRTI) which works through inhibition of reverse transcriptase (RT) RNA-dependent DNA polymerase activity via a direct binding event. To further investigate the relationship between its structure and activity, four series of novel analogues were designed and synthesized with 12 of them inhibiting HIV-1 replication with IC
50 s in the range 0.09-6.71 μM. Compound 4b, 4c, 4f, 2 and 6b were further tested on two NNRTI-resistant HIV-1 strains and one NNRTI-resistant superbug. The result showed that RT- E138K/M184V mutant virus conferred 4.7-9.1-fold resistance to 4c, 4f, 2 and 6b, but only showed slight resistance to 4b (2-fold) which was better than SG-1., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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