Synthesis and Biological Activity of N-(arylsulfonyl) Valine Hydrazones and Assistance of NMR Spectroscopy for Definitive 3D Structure

Author(s): Sevil Şenkardeş, Esra Tatar, Ridvan Nepravishta*, Dorisa Cela, Maurizio Paci, Özlem Bingöl Özakpınar, Turgut Şekerler, Erik De Clercq, Christophe Pannecouque, Ş. Güniz Küçükgüzel*, İlkay Küçükgüzel.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 9 , 2019

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Graphical Abstract:


Abstract:

Background: Hydrazide-hydrazones constitute an important class of compounds for new drug development. In this study, a series of 39 new acylhydrazones (3-41), derived from (2S)-3-methyl- 2-[[(4-methylphenyl)sulfonyl]amino]butanoic acid hydrazide were synthesized with further aim to achieve biologically active acylhydrazones carrying an amino acid side chain.

Methods: Compounds 3-41 were synthesized by microwave-assisted method. All synthesized compounds have been tested for their anti-HIV activity compound 21 was subjected to a new set of 2DNMR analysis for the characterization of the isomers in solution and determination of its 3D structure.

Results: The IC50 values for compounds 2-40 were found between >125-10.90 µg/ml against HIV- 1(IIIB) and HIV-2(ROD) strains in MT-4 cells. Compounds 3, 6, 10, 12, 23, 24, 27, 32, and 37 with CC50 values between 10.90-14.50 µg/ml were selected to evaluate for their antileukemia activity. IC50 values for these mentioned compounds were found as >100μM on human chronic myelogenous leukemia, K562 cell line.

Conclusion: Some compounds with IC50 values between 10.90-14.50 μg/ml will be of benefit in the development of novel leads.

Keywords: Acylhydrazones, anti-HIV activity, antileukemia activity, 2D-NMR spectroscopy, 3D structure, L-valine, microwave assisted synthesis.

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Article Details

VOLUME: 16
ISSUE: 9
Year: 2019
Page: [974 - 983]
Pages: 10
DOI: 10.2174/1570180815666180810120609
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