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

[ Vol. 16 , Issue. 9 ]

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* and İlkay Küçükgüzel   Pages 974 - 983 ( 10 )

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.

Affiliation:

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpasa 34668, Istanbul, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpasa 34668, Istanbul, Dipartimento di Scienze e Technologie Chimiche, Universita di Roma "Tor Vergata", Roma, Dipartimento di Scienze e Technologie Chimiche, Universita di Roma "Tor Vergata", Roma, Dipartimento di Scienze e Technologie Chimiche, Universita di Roma "Tor Vergata", Roma, Department of Biochemistry, Faculty of Pharmacy, Marmara University, Haydarpasa 34668, Istanbul, Department of Biochemistry, Faculty of Pharmacy, Marmara University, Haydarpasa 34668, Istanbul, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpasa 34668, Istanbul, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpasa 34668, Istanbul

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