Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors. 2015

Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 21003, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.

Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized, and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In vitro biological evaluation against three human tumor cell lines revealed that most target compounds showed antiproliferative activities. Among the compounds, compound 48 exhibited the most potent and selective COX-2 inhibitor (COX-2 IC50=0.33 μM; COX-1 IC50=68.49 μM) relative to the reference drugs celecoxib (IC50=0.052 μM). Docking simulation was performed to position compound 48 into the COX-2 active site and the result showed that compound 48 could bind well at the COX-2 active site and it indicated that compound 48 could be a potent and selective COX-2 inhibitor.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs

Related Publications

Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
November 2011, Bioorganic & medicinal chemistry,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
November 2012, Bioorganic & medicinal chemistry,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
January 2022, Molecules (Basel, Switzerland),
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
March 2020, European journal of medicinal chemistry,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
January 2022, Current computer-aided drug design,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
January 2017, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
January 2018, European journal of medicinal chemistry,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
January 2018, Chemical & pharmaceutical bulletin,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
May 2008, Archives of pharmacal research,
Zhong Chen, and Zhong-Chang Wang, and Xiao-Qiang Yan, and Peng-Fei Wang, and Xiao-Yuan Lu, and Long-Wang Chen, and Hai-Liang Zhu, and Hong-Wei Zhang
June 2014, European journal of medicinal chemistry,
Copied contents to your clipboard!