title: Synthesis, antitumor evaluation, molecular modeling and quantitative structure-activity relationship (QSAR) of some novel arylazopyrazolodiazine and triazine analogs.
abstract: The synthesis, in vivo and in vitro antitumor evaluation, and QSAR studies of some novel pyrazole analogs against Ehrlich Ascites Carcinoma (EAC) cells were described. In vitro results revealed that compounds 10, 6 and 4 were the most potent analogs against EAC, respectively. Moreover, in vivo evaluation of compounds 6 and 10 proved their capability to normalize the blood picture in comparison to 5-FU, a well known anticancer drug. These novel pyrazole analogs were molecularly designed with the goal of having significant potent cytotoxic effect against EAC cells. To develop a QSAR model capable of identifying the key molecular descriptors associated with the biological activity of the novel pyrazole analogs and predicting the cytotoxic effect for other novel pyrazole analogs against EAC cells, different QSAR models, using different physicochemical and topological molecular descriptors, were developed. Different molecular descriptors were predicted solely from the chemical structures of 16 pyrazolo-diazine and triazine analogs following the prediction of the equilibrium molecular geometry of each analog at the DFT level using B88-LYP functional energy and double zeta valence polarized (DZVP) basis set. It was found that dipole moment, excitation energy, the energy value of LUMO, solvent accessible surface area, and heat of formation were the key molecular descriptors in descriping the cytotoxic effect of those compounds against EAC.
authors.affiliation: Fiber and Polymer Science Program, North Carolina State University, Raleigh, NC 27695, USA. Ahmed_El-Shafei@ncsu.edu
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Shafei
authors.forename: A A
authors.initials: AA
authors.lastname: Fadda
authors.forename: A M
authors.initials: AM
authors.lastname: Khalil
authors.forename: T A E
authors.initials: TA
authors.lastname: Ameen
authors.forename: Farid A
authors.initials: FA
authors.lastname: Badria
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000401:mortality; D047390:Casein Kinase II / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D021281:Quantitative Structure-Activity Relationship; D013534:Survival; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001391:Azo Compounds; D011720:Pyrazoles; D014227:Triazines; D047390:Casein Kinase II