Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Jul 2

PMID 34201561

Citations 2

Authors

Rita Meleddu

Angela Corona

Simona Distinto

Filippo Cottiglia

Serenella Deplano

Lisa Sequeira

Daniela Secci

Alessia Onali

Erica Sanna

Francesca Esposito

Italo Cirone

Francesco Ortuso

Stefano Alcaro

Enzo Tramontano

Peter Matyus

Elias Maccioni

Affiliations

Soon will be listed here.

Abstract

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide () was the most potent towards RNaseH (IC = 4.5 mM)- and RDDP (IC = 8.0 mM) HIV RT-associated functions.

Citing Articles

5-Nitro-3-(2-(4-phenylthiazol-2-yl)hydrazineylidene)indolin-2-one derivatives inhibit HIV-1 replication by a multitarget mechanism of action.

Corona A, Meleddu R, Delelis O, Subra F, Cottiglia F, Esposito F Front Cell Infect Microbiol. 2023; 13:1193280.

PMID: 37424782 PMC: 10328743. DOI: 10.3389/fcimb.2023.1193280.

Thiazole Ring-A Biologically Active Scaffold.

Petrou A, Fesatidou M, Geronikaki A Molecules. 2021; 26(11).

PMID: 34070661 PMC: 8198555. DOI: 10.3390/molecules26113166.

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