Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide.

doi:10.1021/JM0512490

Paper

Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide.

Published May 3, 2006 · R. Ragno, Antonio Coluccia, G. La Regina

Journal of medicinal chemistry

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142

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Abstract

Molecular modeling studies and an updated highly predictive 3-D QSAR model led to the discovery of exceptionally potent indolyl aryl sulfones (IASs) characterized by the presence of either a pyrrolidyn-2-one nucleus at the indole-2-carboxamide or some substituents at the indole-2-carbohydrazide. Compounds 7 and 9 were found active in the sub-nanomolar range of concentration in both MT-4 and C8166 cell-based anti-HIV assays. These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages.

In Vitro Study

Highly Cited

Study Snapshot

New indolyl aryl sulfones show exceptional anti-HIV-1 activity, with compounds 7 and 9 showing sub-nanomolar activity in cell-based assays.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide.

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References

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The Autodock program effectively reproduces 41 experimental bound conformations of NNRTIs, providing valuable insights for structure-based drug design and understanding the mode of action of new anti-HIV agents against both wild-type and resistant strains.

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Indolyl aryl sulfones show high anti-HIV-1 activity, with new derivatives being designed and tested, enabling prediction of their activity using 3-D QSAR models.

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NNRTIs are essential for first-line treatment of HIV-1 infections, but newer compounds show promise for future anti-HIV-1 drugs.

Citations

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Design, Synthesis, In-Silico and Cytotoxic Studies of Indole Derivatives as Potent BCL-2 Inhibitors

Indole derivatives, specifically b11, show considerable anticancer activity by targeting BCL-2 protein, offering an innovative approach to breast cancer management.

Iodophor-catalyzed sulfenylation of indoles with sulfonyl hydrazides for the synthesis of 3-sulfenylindoles

Iodophor-catalyzed sulfenylation of indoles with sulfonyl hydrazides effectively synthesizes 3-sulfenylindoles in aqueous phase, offering an inexpensive, environmentally friendly, and easy method for synthesis

Simple and efficient synthesis of pyrrolo[3,2‐f]quinoxaline derivatives via three‐component reaction

A three-component domino reaction enables the efficient synthesis of pyrrolo[3,2f]quinoxaline derivatives with excellent regioselectivity, operational simplicity, and mild reaction conditions.

Regioselective Thiolation of Indoles with Sulfinyl Amides

This study presents a mild, efficient, and regioselective method for synthesis of 3'-indole thioethers and 2,3'-dithioindole derivatives using sulfinyl amides.

Selective Synthesis of 3‐Chalcogenylindoles via Silver‐Catalyzed Direct Chalcogenation of Indoles with Dichalcogenides

Silver-catalyzed direct chalcogenation of indoles with alcogenides efficiently synthesizes 3'-selenyl and 3'-sulfenyl indoles in a scalable, economical, and eco-friendly manner.

Dehydroaromatization of Indolines and Cyclohexanones with Thiol Access to Aryl Sulfides under Basic Conditions.

This study presents a simple, environmentally friendly method for synthesis of diaryl sulfide derivatives with wide functional groups using air as an oxidant, yielding good to excellent yields.