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KMID : 0043320120350091543
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Archives of Pharmacal Research
2012 Volume.35 No. 9 p.1543 ~ p.1552
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Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity
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Abdel Aziz Hatem A.
Aboul Fadl Tarek
Al Obaid Abdul Rahman M.
Ghazzali Mohamed
Al Dhfyan Abdullah
Contini Alessandro
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Abstract
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Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory activities were obtained with IC50 range from 24.99 to 66.78 μM where the compound 6c exhibited the maximum activity. Structure activity relationship analysis has been performed and a common pharmacophore model for the synthesized derivatives has been obtained by using the pharmacophore elucidation module of the software MOE. The best model obtained is characterized by two projected locations of potential H-bond donors (F 3 and F4) and two Aromatic annotations (F1 and F2).
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KEYWORD
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Nicotinic acid hydrazones, X-ray single crystal diffraction, K 562 Leukemia cell line, Antiproliferative, Molecular modeling, Pharmacophore model building
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