title: Synthesis, docking and biological activities of novel hybrids celecoxib and anthraquinone analogs as potent cytotoxic agents.
abstract: Herein, novel hybrid compounds of celecoxib and 2-aminoanthraquinone derivatives have been synthesized using condensation reactions of celecoxib with 2-aminoanthraquinone derivatives or 2-aminoanthraquinon with celecoxib derivatives. Celecoxib was reacted with different acid chlorides, 2-chloroethylisocyanate and bis (2-chloroethyl) amine hydrochloride. These intermediates were then reacted with 2-aminoanthraquinone. Also the same different acid chlorides and 2-chloroethylisocyanate were reacted with 2-aminoanthraquinone and the resulting intermediates were reacted with celecoxib to give isomers for the previous compounds. The antitumor activities against hepatic carcinoma tumor cell line (HEPG2) have been investigated in vitro, and all these compounds showed promising activities, especially compound 3c, 7, and 12. Flexible docking studies involving AutoDock 4.2 was investigated to identify the potential binding affinities and the mode of interaction of the hybrid compounds into two protein tyrosine kinases namely, SRC (Pp60v-src) and platelet-derived growth factor receptor, PDGFR (c-Kit). The compounds in this study have a preferential affinity for the c-Kit PDGFR PTK over the non-receptor tyrosine kinase SRC (Pp60v-src).
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. malmutairi30@gmail.com.
authors.forename: Maha S
authors.initials: MS
authors.lastname: Almutairi
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. gehan_hegazy@gmail.com.
authors.forename: Gehan H
authors.initials: GH
authors.lastname: Hegazy
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. solimanmohsen@yahoo.com.
authors.forename: Mogedda E
authors.initials: ME
authors.lastname: Haiba
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA. hamed_ali37@yahoo.com.
authors.forename: Hamed I
authors.initials: HI
authors.lastname: Ali
authors.affiliation: Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. solimanmohsen@yahoo.com.
authors.forename: Nagy M
authors.initials: NM
authors.lastname: Khalifa
authors.affiliation: Department of Therapeutical Chemistry, Pharmaceutical and Drug Industries Division, National Research Center, Dokki, Cairo 12622, Egypt. solimanmohsen@yahoo.com.
authors.forename: Abd El-mohsen M
authors.initials: Ael-M
authors.lastname: Soliman
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D011720:Pyrazoles; D013449:Sulfonamides; D011505:Protein-Tyrosine Kinases; D000068579:Celecoxib