title: Synthesis, biological evaluation, and molecular docking studies of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives as novel anticancer agents.
abstract: A series of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives (5a-8d) have been designed and synthesized, and their biological activities were also evaluated as potential antitumor and cyclin dependent kinase 2 (CDK2) inhibitors. Among all the compounds, compound 5a displayed the most potent CDK2/cyclin E inhibitory activity in vitro, with an IC(50) of 0.98 ± 0.06 μM. Antitumor assays indicated that compound 5a owned high antiproliferative activity against MCF-7 and B16-F10 cancer cell lines with IC(50) values of 1.88 ± 0.11 and 2.12 ± 0.15 μM, respectively. Docking simulation was performed to insert compound 5a into the crystal structure of CDK2 at active site to determine the probable binding model. Based on the preliminary results, compound 5a with potent inhibitory activity in tumor growth may be a potential anticancer agent.
authors: School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164, People's Republic of China.
authors: Xian-Feng
authors: XF
authors: Huang
authors: Xiang
authors: X
authors: Lu
authors: Yong
authors: Y
authors: Zhang
authors: Guo-Qiang
authors: GQ
authors: Song
authors: Qi-Long
authors: QL
authors: He
authors: Qing-Shan
authors: QS
authors: Li
authors: Xian-Hui
authors: XH
authors: Yang
authors: Yao
authors: Y
authors: Wei
authors: Hai-Liang
authors: HL
authors: Zhu
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C578218:N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline; D011720:Pyrazoles; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2