title: Synthesis, biological active molecular design, and molecular docking study of novel deazaflavin-cholestane hybrid compounds.
abstract: 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).
authors: Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 1-1-1, Tsushima-naka, Okayama 700-8530, Japan.
authors: Ajaya R
authors: AR
authors: Shrestha
authors: Takashi
authors: T
authors: Shindo
authors: Noriyuki
authors: N
authors: Ashida
authors: Tomohisa
authors: T
authors: Nagamatsu
mesh_terms: 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
chemical_list: D002776:Cholestanes; D005415:Flavins; D008024:Ligands; C019319:5-deazaflavin; D011505:Protein-Tyrosine Kinases