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

• Published in: Archives of pharmacal research Vol. 35; no. 9; pp. 1543 - 1552
• Main Authors: Abdel-Aziz, Hatem A., Aboul-Fadl, Tarek, Al-Obaid, Abdul-Rahman M., Ghazzali, Mohamed, Al-Dhfyan, Abdullah, Contini, Alessandro
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01.09.2012; 대한약학회
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Crystallography, X-Ray; Drug Design; Humans; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Hydrogen Bonding; Leukemia, Myeloid, Chronic-Phase - drug therapy; Magnetic Resonance Spectroscopy; Medicine; Models, Molecular; Molecular Conformation; Molecular Structure; Nicotinic Acids - chemical synthesis; Nicotinic Acids - chemistry; Nicotinic Acids - pharmacology; Osmolar Concentration; Pharmacology/Toxicology; Pharmacy; Research Article; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Transition Temperature; 약학; Antiproliferative; Pharmacophore model building; K 562 Leukemia cell line; Molecular modeling; Nicotinic acid hydrazones; X-ray single crystal diffraction
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-012-0904-2

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 IC 50 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).