title: Synthesis, Biological Evaluation, and Docking of Dihydropyrazole Sulfonamide Containing 2-hydroxyphenyl Moiety: A Series of Novel MMP-2 Inhibitors.
abstract: In this study, we synthesized a series of dihydropyrazole sulfonamide derivatives containing 2-hydroxyphenyl moiety as antitumor agents to target the matrix metalloproteinase-2 (MMP-2). All of the synthesized compounds were examined by bioactivity assays, in which compound 4c turned out as a potential antagonist of MMP-2 along with potent anticancer activity against four tumor cell lines. Structure-activity relationship analysis was also performed to examine how structural changes impacted the bioactivity. Suggested to be caused by the induction of apoptosis, the antitumor mechanism of 4c was further confirmed by PI combining with annexin V-FITC staining assay using flow cytometry analysis. These new findings along with molecular docking observations suggested that compound 4c could be developed as a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Han-Yue
authors.initials: HY
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.|Department of Biotechnology, FCPD, Sindh Agriculture University, Tandojam, Sindh, Pakistan.
authors.forename: Shahla Karim
authors.initials: SK
authors.lastname: Baloch
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.|Xuzhou Central Hospital, Xuzhou, 221009, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Zhong-Chang
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D013449:Sulfonamides; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: MMP-2; anticancer; dihydropyrazole sulfonamide; extracellular matrix enzyme; flow cytometry analysis