Unknown

Dataset Information

0

Synthesis, docking, and biological studies of phenanthrene ?-diketo acids as novel HIV-1 integrase inhibitors.

ABSTRACT: In the present study we report the synthesis of halogen-substituted phenanthrene ?-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6-Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound of the series, inhibiting both 3'-end processing (3'-P) and strand transfer (ST) with IC50 values of 5 and 1.3 ?M, respectively. Docking studies revealed two predominant binding modes that were distinct from the binding modes of raltegravir and elvitegravir, and suggest a novel binding region in the IN active site. Moreover, these compounds are predicted not to interact significantly with some of the key amino acids (Q148 and N155) implicated in viral resistance. Therefore, this series of compounds can further be investigated for a possible chemotype to circumvent resistance to clinical HIV-1 IN inhibitors.

SUBMITTER: Sharma H 

PROVIDER: S-EPMC3866047 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Synthesis, docking, and biological studies of phenanthrene β-diketo acids as novel HIV-1 integrase inhibitors.

Sharma Horrick H   Sanchez Tino W TW   Neamati Nouri N   Detorio Mervi M   Schinazi Raymond F RF   Cheng Xiaolin X   Buolamwini John K JK  

Bioorganic & medicinal chemistry letters 20130911 22

In the present study we report the synthesis of halogen-substituted phenanthrene β-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6-Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound of the series, inhibiting both 3'-end processing (3'-P) and strand transfer (ST) with IC50 values of 5 and 1.3 μM, respectively. Docking studies revealed two predominant binding mod  ...[more]

Similar Datasets

Unknown Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: design, synthesis, and biological activities.
| S-EPMC2646871 | biostudies-other
Unknown Novel bifunctional quinolonyl diketo acid derivatives as HIV-1 integrase inhibitors: design, synthesis, biological activities, and mechanism of action.
| S-EPMC2602756 | biostudies-literature
Unknown Docking studies of flavonoid derivatives as potent HIV-1 integrase inhibitors
| S-EPMC4080103 | biostudies-literature
Unknown Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of ?-Diketo Acids.
| S-EPMC6332332 | biostudies-literature
Unknown Design, Synthesis, and Biological Evaluation of 1,2-Dihydroisoquinolines as HIV-1 Integrase Inhibitors.
| S-EPMC4601057 | biostudies-literature
Unknown Indole Derivatives as Cyclooxygenase Inhibitors: Synthesis, Biological Evaluation and Docking Studies.
| S-EPMC6100013 | biostudies-literature
Unknown Binding modes of diketo-acid inhibitors of HIV-1 integrase: a comparative molecular dynamics simulation study.
| S-EPMC3101338 | biostudies-literature
Unknown Selective Acetamidine-Based Nitric Oxide Synthase Inhibitors: Synthesis, Docking, and Biological Studies.
| S-EPMC4468396 | biostudies-literature
Unknown 5,6-Benzoflavones as cholesterol esterase inhibitors: synthesis, biological evaluation and docking studies.
| S-EPMC6072486 | biostudies-literature
Unknown Design, synthesis and structure-activity studies of rhodanine derivatives as HIV-1 integrase inhibitors.
| S-EPMC6264390 | biostudies-literature