Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity.
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).
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Hatem A
HA
Abdel-Aziz
Tarek
T
Aboul-Fadl
Abdul-Rahman M
AR
Al-Obaid
Mohamed
M
Ghazzali
Abdullah
A
Al-Dhfyan
Alessandro
A
Contini
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009539:Nicotinic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009994:Osmolar Concentration; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D044366:Transition Temperature
D000970:Antineoplastic Agents; D006835:Hydrazones; D009539:Nicotinic Acids