Some Hydrazones of 2‐Aroylamino‐3‐methylbutanohydrazide: Synthesis,Molecular Modeling Studies,and Identification as Stereoselective Inhibitors of HIV‐1 |
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| Authors: | Esra Tatar İlkay Küçükgüzel Dirk Daelemans Tanaji T. Talele Neerja Kaushik‐Basu Erik De Clercq Christophe Pannecouque |
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| Affiliation: | 1. Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Marmara University, Haydarpa?a, ?stanbul, Turkey;2. Rega Institute for Medical Research, KU Leuven, Leuven, Belgium;3. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, USA;4. Department of Biochemistry and Molecular Biology, UMDNJ‐New Jersey Medical School, Newark, NJ, USA |
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| Abstract: | In accordance with our antiviral drug development attempt, acylhydrazone derivatives bearing amino acid side chains were synthesized for the evaluation of their antiviral activity against various types of viruses. Among these compounds, 8 S , 11 S , and 12 S showed anti‐HIV‐1 activity with a 50% inhibitory concentration (IC50) = 123.8 µM (selectivity index, SI > 3), IC50 = 12.1 µM (SI > 29), IC50 = 17.4 µM (SI > 19), respectively. Enantiomers 8 R , 11 R , and 12 R were inactive against the HIV‐1 strain IIIB. Hydrazones 8 S , 11 S , and 12 S which were active against HIV‐1 wild type showed no inhibition against a double mutant NNRTI‐resistant strain (K103N;Y181C). Molecular docking calculations of R‐ and S‐enantiomers of 8 , 11 , and 12 were performed using the hydrazone‐bound novel site of HIV‐1 RT. |
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