BIOMAT Database Logo BIOMAT Database Logo

Design, synthesis and biological evaluation of some novel benzothiazole/benzoxazole and/or benzimidazole derivatives incorporating a pyrazole scaffold as antiproliferative agents. 2017

Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka, Aljouf 2014, Saudi Arabia. Electronic address: Mohamedabdelwahab976@yahoo.com.

In an aim at developing new antiproliferative agents, new series of benzothiazole/benzoxazole and/or benzimidazole substituted pyrazole derivatives 11a-c, 12a-c and 13a-c were prepared and evaluated for their antiproliferative activity against breast carcinoma (MCF-7) and non-small cell lung cancer (A549) cell lines. The target compound, 2-acetyl-4-[(3-(1H-benzimidazol-2-yl)-phenyl]-hydrazono-5-methyl-2,4-dihydropyrazol-3-one (12a) was the most active compound against both MCF-7 and A549 cell lines with half maximal inhibitory concentrations (IC50)=6.42 and 8.46μM, respectively. Furthermore, the inhibitory activity of the all the target compounds against COX enzymes was recorded as a proposed mechanism for their antiproliferative activity. The obtained results revealed that the benzothiazolopyrazolone derivative 13c was the most potent COX-2 inhibitor (IC50=0.10μM), while the 5-acetylbenzimidazolylpyrazolone derivative 12a was the most COX-2 selective (S.I.=104.67) in comparison with celecoxib (COX-2 IC50=1.11μM, S.I.=13.33). Docking simulation on the most active compounds 12a and 13c had been performed to investigate the binding interaction of these active compounds within the binding site of COX-2 enzyme.Collectively, this work demonstrated the promising activity of the newly designed compounds as leads for further development into antiproliferative agents.

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.
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
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
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
D001562 Benzimidazoles Compounds with a BENZENE fused to IMIDAZOLES.
D001583 Benzoxazoles Benzoxazole
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

Related Publications

Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Design, synthesis and biological evaluation of benzimidazole/benzothiazole and benzoxazole derivatives as cyclooxygenase inhibitors.
February 2003, Bioorganic & medicinal chemistry letters,
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Novel benzothiazole, benzimidazole and benzoxazole derivatives as potential antitumor agents: synthesis and preliminary in vitro biological evaluation.
January 2012, Molecules (Basel, Switzerland),
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Novel flavonol derivatives containing benzoxazole as potential antiviral agents: design, synthesis, and biological evaluation.
January 2024, Molecular diversity,
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Design, synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory-antimicrobial agents.
April 2004, Bioorganic & medicinal chemistry,
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Synthesis and Biological Evaluation of Novel Amino and Amido Substituted Pentacyclic Benzimidazole Derivatives as Antiproliferative Agents.
February 2024, International journal of molecular sciences,
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Synthesis and in vitro antiproliferative evaluation of some B-norcholesteryl Benzimidazole and Benzothiazole derivatives.
April 2015, Marine drugs,
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Design, Synthesis and Antiproliferative Activity of Novel Benzothiazole Derivatives Conjugated with Semicarbazone Scaffold.
January 2016, Medicinal chemistry (Shariqah (United Arab Emirates)),
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Design, Synthesis, and Biological Evaluation of 6-Benzoxazole Benzimidazole Derivatives with Antihypertension Activities.
January 2019, ACS medicinal chemistry letters,
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Design, synthesis, antimicrobial activity and computational studies of novel azo linked substituted benzimidazole, benzoxazole and benzothiazole derivatives.
February 2019, Computational biology and chemistry,
Mohamed A Abdelgawad, and Rania B Bakr, and Hany A Omar
Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Potential Anticonvulsant Agents.
February 2016, Molecules (Basel, Switzerland),
Copied contents to your clipboard!