Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity

作者：Abdel Aziz Hatem A; Aboul Fadl Tarek^*; Al Obaid Abdul Rahman M; Ghazzali Mohamed; Al Dhfyan Abdullah; Contini Alessandro

来源：Archives of Pharmacal Research, 2012, 35(9): 1543-1552.

DOI：10.1007/s12272-012-0904-2

• Nicotinic acid hydrazones
• X-ray single crystal diffraction
• K562 Leukemia cell line
• Antiproliferative
• Molecular modeling
• Pharmacophore model building

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 mu M 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).

• 出版日期2012-9