Transposition of the pyridyl nitrogen from the P(3) substituent to the P(1)' substituent in HIV-1 protease inhibitors (PI) affords compounds such as 3 with an improved inhibitory profile against multiple P450 isoforms. These compounds also displayed increased potency, with 3 inhibiting viral spread (CIC(95)) at <8 nM for every strain of PI-resistant HIV-1 tested. The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0960-894x(03)00680-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HIV OctaScanner: A Machine Learning Approach to Unveil Proteolytic Cleavage Dynamics in HIV-1 Protease Substrates.
J Chem Inf Model
January 2025
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
The rise of resistance to antiretroviral drugs due to mutations in human immunodeficiency virus-1 (HIV-1) protease is a major obstacle to effective treatment. These mutations alter the drug-binding pocket of the protease and reduce the drug efficacy by disrupting interactions with inhibitors. Traditional methods, such as biochemical assays and structural biology, are crucial for studying enzyme function but are time-consuming and labor-intensive.
View Article and Find Full Text PDFRitonavir enhances the efficacy of amprenavir: A promising combination therapy by targeting Leishmania DNA topoisomerase I for treatment of visceral leishmaniasis.
Exp Parasitol
January 2025
Department of Biotechnology, Savitribai Phule Pune University, 411007, Pune, India. Electronic address:
Visceral leishmaniasis (VL) is an opportunistic infection in HIV patients with higher relapse and mortality rate. The number of HIV-VL patients is comparatively higher in areas where both infections are endemic. However, the conventional chemotherapeutic agents have limited success due to drug toxicity, efficacy variance and overall cost of treatment.
View Article and Find Full Text PDFSynergistic inhibition of HIV-1 by Nelfinavir and Epigallocatechin Gallate: A novel nanoemulsion-based therapeutic approach.
Virology
January 2025
Division of Virology, ICMR-National Institute of Translational and AIDS Research Institute, Pune, India; AcSIR - Academy of Scientific & Innovative Research, Ghaziabad, India. Electronic address:
The integration of nanotechnology into antiretroviral drug delivery systems presents a promising avenue to address challenges posed by long-term antiretroviral therapies (ARTs), including poor bioavailability, drug-induced toxicity, and resistance. These limitations impact the therapeutic effectiveness and quality of life for individuals living with HIV. Nanodrug delivery systems, particularly nanoemulsions, have demonstrated potential in improving drug solubility, enhancing bioavailability, and minimizing systemic toxicity.
View Article and Find Full Text PDFMechanism and Kinetics of HIV-1 Protease Activation.
Viruses
November 2024
Center for Proteomics and Bioinformatics, Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
The HIV-1 protease is a critical enzyme for viral replication. Because protease activity is necessary to generate mature infectious virions, it is a primary target of antiretroviral treatment. Here, we provide an overview of the mechanisms regulating protease activation and the methods available to assess protease activity.
View Article and Find Full Text PDFHigh prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana.
J Antimicrob Chemother
January 2025
Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.
Objectives: We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.
Methods: The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL).
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!