Rational Design, Synthesis, and Biological Evaluation of Novel Thiazole/Thiazolidinones Multitarget Anti-Human Immunodeficiency Virus Molecules DOI Creative Commons
Christophe Tratrat, Anthi Petrou, Maria Fesatidou

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 298 - 298

Опубликована: Фев. 21, 2025

Background: HIV-1 RT inhibitors were the first drugs approved to treat AIDS and remain key components of highly active antiretroviral therapy (HAART). While HAART effectively suppresses viral replication slows disease progression, it has limitations, including long-term side effects emergence drug-resistant strains, highlighting need for new treatments. Objectives: Based on our previous experience, insights from existing RNase H, we aim design synthesize safer, multifunctional molecules. Methods: Using molecular docking studies, these compounds will incorporate pharmacophores targeting multiple stages HIV life cycle enhance efficacy, reduce resistance, improve pharmacokinetics. The synthesized via a one-pot three component reaction. identified using spectroscopy tested in vitro activity against targets, RNA-dependent DNA polymerase (RDDP) RNAse H. Results: Among compounds, several demonstrated strong inhibitory activity, with compound 11 showing IC50 values comparable reference drug Nevirapine, 4 exhibiting dual inhibition both H activities. Conclusions: These findings emphasize importance multidisciplinary approach, combining computational modeling experimental validation, identify promising leads therapeutic development.

Язык: Английский

Rational Design, Synthesis, and Biological Evaluation of Novel Thiazole/Thiazolidinones Multitarget Anti-Human Immunodeficiency Virus Molecules DOI Creative Commons
Christophe Tratrat, Anthi Petrou, Maria Fesatidou

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 298 - 298

Опубликована: Фев. 21, 2025

Background: HIV-1 RT inhibitors were the first drugs approved to treat AIDS and remain key components of highly active antiretroviral therapy (HAART). While HAART effectively suppresses viral replication slows disease progression, it has limitations, including long-term side effects emergence drug-resistant strains, highlighting need for new treatments. Objectives: Based on our previous experience, insights from existing RNase H, we aim design synthesize safer, multifunctional molecules. Methods: Using molecular docking studies, these compounds will incorporate pharmacophores targeting multiple stages HIV life cycle enhance efficacy, reduce resistance, improve pharmacokinetics. The synthesized via a one-pot three component reaction. identified using spectroscopy tested in vitro activity against targets, RNA-dependent DNA polymerase (RDDP) RNAse H. Results: Among compounds, several demonstrated strong inhibitory activity, with compound 11 showing IC50 values comparable reference drug Nevirapine, 4 exhibiting dual inhibition both H activities. Conclusions: These findings emphasize importance multidisciplinary approach, combining computational modeling experimental validation, identify promising leads therapeutic development.

Язык: Английский

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