The design and synthesis of a pyrrole-carbaldehyde hit family as HIV-1 integrase inhibitors

Screening of an HIV-1 IN model against database-derived chemical structures identified pyrrole-carbaldehydes as targets for further development. Chemical synthesis using a facile one-pot reaction resulted in the generation of a compound library. Preliminary toxicity and efficacy assays of the water-soluble HCl-salt derivatives of each compound support the in silico predictions.

Download Full-text

Design and Synthesis of Bis-amide and Hydrazide-containing Derivatives of Malonic Acid as Potential HIV-1 Integrase Inhibitors

Molecules ◽

10.3390/molecules13102442 ◽

2008 ◽

Vol 13 (10) ◽

pp. 2442-2461 ◽

Cited By ~ 23

Author(s):

Mario Sechi ◽

Ugo Azzena ◽

Maria Paola Delussu ◽

Roberto Dallocchio ◽

Alessandro Dessì ◽

...

Keyword(s):

Malonic Acid ◽

Integrase Inhibitors ◽

Design And Synthesis ◽

Derivatives Of ◽

Hiv 1

Download Full-text

Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors

Acta Naturae ◽

10.32607/20758251-2013-5-1-63-72 ◽

2013 ◽

Vol 5 (1) ◽

pp. 63-72 ◽

Cited By ~ 18

Author(s):

S. P. Korolev ◽

O. V. Kondrashina ◽

D. S. Druzhilovsky ◽

A. M. Starosotnikov ◽

M. D. Dutov ◽

...

Keyword(s):

Integrase Inhibitor ◽

Integrase Inhibitors ◽

Mechanism Of Inhibition ◽

Immunodeficiency Virus ◽

Pharmacokinetic Properties ◽

Nitro Derivatives ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

Human immunodeficiency virus type 1 integrase is one of the most attractive targets for the development of anti-HIV-1 inhibitors. The capacity of a series of 2,1,3-benzoxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) selected using the PASS software to inhibit the catalytic activity of HIV-1 integrase was studied in the present work. Only the nitro-derivatives of these compounds were found to display inhibitory activity. The study of the mechanism of inhibition by nitro-benzofurazans/benzofuroxans showed that they impede the substrate DNA binding at the integrase active site. These inhibitors were also active against integrase mutants resistant to raltegravir, which is the first HIV-1 integrase inhibitor approved for clinical use. The comparison of computer-aided estimations of the pharmacodynamic and pharmacokinetic properties of the compounds studied and raltegravir led us to conclude that these compounds show promise and need to be further studied as potential HIV-1 integrase inhibitors.

Download Full-text

Design and synthesis of novel water-soluble amino acid derivatives of chlorin p6 ethers as photosensitizer

Chinese Chemical Letters ◽

10.1016/j.cclet.2018.04.029 ◽

2019 ◽

Vol 30 (1) ◽

pp. 247-249 ◽

Cited By ~ 6

Author(s):

Xingjie Zhang ◽

Zhi Meng ◽

Zhiqiang Ma ◽

Junhong Liu ◽

Guiyan Han ◽

...

Keyword(s):

Amino Acid ◽

Water Soluble ◽

Amino Acid Derivatives ◽

Design And Synthesis ◽

Derivatives Of ◽

Chlorin P6

Download Full-text

Design and Synthesis of Novel Indole β-Diketo Acid Derivatives as HIV-1 Integrase Inhibitors

Journal of Medicinal Chemistry ◽

10.1021/jm049944f ◽

2004 ◽

Vol 47 (21) ◽

pp. 5298-5310 ◽

Cited By ~ 89

Author(s):

Mario Sechi ◽

Massimiliano Derudas ◽

Roberto Dallocchio ◽

Alessandro Dessì ◽

Alessia Bacchi ◽

...

Keyword(s):

Integrase Inhibitors ◽

Design And Synthesis ◽

Hiv 1

Download Full-text

Design and Synthesis of Photoactivatable Aryl Diketo Acid-Containing HIV-1 Integrase Inhibitors (I) as Potential Affinity Probes.

ChemInform ◽

10.1002/chin.200423100 ◽

2004 ◽

Vol 35 (23) ◽

Author(s):

Xuechun Zhang ◽

Christophe Marchand ◽

Yves Pommier ◽

Terrence R. Jr. Burke

Keyword(s):

Integrase Inhibitors ◽

Design And Synthesis ◽

Affinity Probes ◽

Hiv 1

Download Full-text

Synthesis and anti-HIV Activity of New Benzimidazole, Benzothiazole and Carbohyrazide Derivatives of the anti-Inflammatory Drug Indomethacin

Zeitschrift für Naturforschung B ◽

10.1515/znb-2011-0914 ◽

2011 ◽

Vol 66 (9) ◽

pp. 953-960 ◽

Cited By ~ 2

Author(s):

Najim A. Al-Masoudi ◽

Nadhir N. A. Jafar ◽

Layla J. Abbas ◽

Sadiq J. Baqir ◽

Christophe Pannecouque

Keyword(s):

Phenyl Isothiocyanate ◽

Reverse Transcriptase Inhibitors ◽

Inflammatory Drug ◽

Oxadiazole Derivatives ◽

Anti Inflammatory ◽

New Compounds ◽

Further Development ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

There is an urgent need for the design and development of new and safer drugs for the treatment of HIV infection, active against the currently resistant viral strains. New derivatives of the non-steroidal anti-inflammatory drug indomethacin bearing benzimidazoles, benzothiazole, purine and pyridine residues 8 - 13 were synthesized with the aim of developing new non-nucleoside reverse transcriptase inhibitors (NNRTIs).Alternatively, new imine analogs 16 - 20 were synthesized from condensation of indomethacinyl hydrazide 15, prepared from the ester 14, with various ketone precursors. Treatment of 15 with phenyl isothiocyanate or triethyl orthoformate afforded the phenylcarbonothioyl and the oxadiazole derivatives 21 and 22, respectively. The new compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 9 and 10 were the most active in inhibiting HIV-2 and HIV-1, respectively, with EC50 ≥ 17.60 μgmL−1 and > 1.15 μgmL−1 (therapeutic indexes (SI) of ≥ 3 and < 1, respectively), and are leading candidates for further development.

Download Full-text