AI Article Synopsis
- Researchers are focusing on developing new drugs that mimic essential properties for inhibiting HIV-1 integrase.
- The study reports the creation of 35 novel compounds derived from a previously studied chemical scaffold, enhancing their effectiveness against HIV-1.
- Two specific compounds, 9g and 15i, demonstrate strong antiviral activity with low toxicity, indicating they could be promising candidates for further development as anti-HIV-1 treatments.
Article Abstract
The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN) inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenyl)ethyl]-pyrrole-2,5-dione scaffolds to design 35 novel compounds with improved biological activities against HIV-1. These new compounds show single-digit micromolar antiviral potencies against HIV-1 and low toxicity. Among of them, compound 9g and 15i had potent anti-HIV-1 activities (EC50 < 5 μM) and excellent therapeutic index (TI, CC50/EC50 > 100). These two compounds have potential as lead compounds for further optimization into clinical anti-HIV-1 agents.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274355 | PMC |
| http://dx.doi.org/10.3390/molecules21091198 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.
Commun Biol
December 2024
Institut national de la recherche scientifique (INRS)-Centre Armand-Frappier Santé Biotechnologie, 531 boulevard des Prairies, H7V 1M7, Laval, QC, Canada.
We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.
View Article and Find Full Text PDFAmides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects.
RSC Med Chem
October 2024
Institute of Experimental Botany of the Czech Academy of Sciences, Isotope Laboratory Vídeňská 1083 14220 Prague 4 Czech Republic
A series of amides of selected plant triterpenoids, moronic acid and morolic acid, with the tripeptides MAG and GAM, was designed and synthesized. Two required tripeptides 5 and 10 were synthesized by a step-wise chain elongation of the ethyl esters of either glycine or l-methionine at their N-terminus using Boc-protected amino acids in each step. The tripeptides 5 and 10 were used for the synthesis of 13-23, the derivatives of moronic acid (11) and morolic acid (12), to get a series of amide derivatives of the less frequently studied triterpenoids 11 and 12.
View Article and Find Full Text PDFDesign of coiled-coil N-peptides against HIV-1 based on a CADD strategy.
Org Biomol Chem
December 2024
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P.R. China.
Human Immunodeficiency Virus (HIV) has continued to endanger human health for decades and has a substantial impact on global health defence. Peptide-based fusion inhibitors, as an integral part of Highly Active Anti-Retroviral Therapy (HAART), are effective in preventing and controlling the AIDS epidemic. Nevertheless, the current market leader, Enfuvirtide, is facing numerous challenges in clinical application.
View Article and Find Full Text PDFExpanding the Solvent/Protein Region Occupation of the Non-Nucleoside Reverse Transcriptase Inhibitor Binding Pocket for Improved Broad-Spectrum Anti-HIV-1 Efficacy: from Rigid Phenyl-Diarylpyrimidines to Flexible Hydrophilic Piperidine-Diarylpyrimidines.
J Med Chem
November 2024
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China.
Considering the nonideal antiresistance efficacy of our previously reported non-nucleoside reverse transcriptase inhibitor , a series of novel piperidine-diarylpyrimidine derivatives were designed through expanding solvent/protein region occupation. The representative compound proved to be exceptionally potent against Y188L (EC = 23 nM), F227L + V106A (EC = 15 nM) and RES056 (EC = 45 nM), significantly better than . This analog exerted strong inhibition against wild-type HIV-1 (EC = 3 nM) and single mutant strains (L100I, K103N, Y181C, E138 K).
View Article and Find Full Text PDFIFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway.
J Virol
November 2024
State Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
Article Synopsis
- Type I interferon (IFN-I) and its gene IFI27 are crucial in controlling HIV-1 infection by effectively suppressing viral replication and degrading its proteins, p24 and p55.
- The study found that the IFI27 variant from northern pig-tailed macaques (NPM-IFI27) is particularly effective against HIV-1, utilizing the ubiquitin-proteasome pathway to target and degrade viral proteins.
- These results highlight the potential of NPM-IFI27 as a promising candidate for new antiviral therapies against HIV-1, emphasizing the need for ongoing research in host antiviral agents.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!