title: Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors.
abstract: A series of novel benzohydrazide derivatives containing dihydropyrazoles have been synthesized as potential epidermal growth factor receptor (EGFR) kinase inhibitors and their biological activities as potential antiproliferative agents have been evaluated. Among these compounds, compound H20 exhibited the most potent antiproliferative activity against four cancer cell line variants (A549, MCF-7, HeLa, HepG2) with IC50 values of 0.46, 0.29, 0.15 and 0.21 μM respectively, which showed the most potent EGFR inhibition activities (IC50 = 0.08 μM for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity and activity relationship (SAR) of these benzohydrazide derivatives. These results suggested that compound H20 may be a promising anticancer agent.
authors.affiliation: College of Biology and Food Engineering, Suzhou University, Suzhou 234000, China. wanghc0823@163.com.|State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China. wanghc0823@163.com.
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China. 18120176083@163.com.
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China. ytlnju@163.com.
authors.forename: Tian-Long
authors.initials: TL
authors.lastname: Yan
authors.affiliation: College of Biology and Food Engineering, Suzhou University, Suzhou 234000, China. hxl96hx@163.com.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China. wangzhongchang2006@163.com.
authors.forename: Zhong-Chang
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China. zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000072283:A549 Cells; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR inhibitor; antiproliferative activity; benzohydrazide derivatives; cytotoxicity; molecular docking