AI Article Synopsis
- Researchers developed new chiral indolyarylsulfones (IASs) that effectively inhibit various strains of HIV-1, including both wild type and mutant strains.
- They successfully separated racemic mixtures into pure enantiomers, finding that (R)-8 was more effective in inhibiting HIV-1 compared to its (S)-version.
- Additionally, certain IAS derivatives demonstrated neuroprotective properties, unlike the existing drug efavirenz, suggesting these new compounds could offer both improved antiviral effects and less neurotoxicity.
Article Abstract
We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8-37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N-Y181C HIV-1 strains. Six racemic mixtures, 8, 23-25, 31, and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31, and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers. Compound 23 protected hippocampal neuronal cells from the excitotoxic insult, while efavirenz (EFV) did not contrast the neurotoxic effect of glutamate. The present results highlight the chiral IASs as new NNRTIs with improved resistance profile against the mutant HIV-1 strains and reduced neurotoxic effects.
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| http://dx.doi.org/10.1021/acs.jmedchem.6b01906 | DOI Listing |
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