Synthesis, biological active molecular design, and molecular docking study of novel deazaflavin-cholestane hybrid compounds.
Novel deazaflavin-cholestane hybrid compounds, 3',8'-disubstituted-5'-deazacholest-2,4-dieno[2,3-g]pteridine-2',4'(3'H,8'H)-diones, have been synthesized by condensation reaction between 6-(monosubstituted amino)-pyrimidin-2,4(1H,3H)-diones and 2-hydroxymethylenecholest-4-en-3-one in presence of p-toluenesulfonic acid monohydrate and diphenyl ether. The antitumor activities against human tumor cell lines (CCRF-HSB-2 and KB cells) have been investigated in vitro, and many of these compounds showed promising antitumor activities. Furthermore, molecular docking study using LigandFit within the software package Discovery Studio 1.7 was done for lead optimization of these compounds as potential PTK inhibitors. In general, all of the synthesized steroid-hybrid compounds showed good binding affinities into PTK (PDB code: 1t46).
Shrestha
Ajaya R
AR
Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 1-1-1, Tsushima-naka, Okayama 700-8530, Japan.
Shindo
Takashi
T
Ashida
Noriyuki
N
Nagamatsu
Tomohisa
T
D000465:Algorithms; D001665:Binding Sites; D045744:Cell Line, Tumor; D002776:Cholestanes / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D005415:Flavins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008958:Models, Molecular; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D002776:Cholestanes; D005415:Flavins; D008024:Ligands; C019319:5-deazaflavin; D011505:Protein-Tyrosine Kinases