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Dihydropyrazole Derivatives Containing Benzo Oxygen Heterocycle and Sulfonamide Moieties Selectively and Potently Inhibit COX-2: Design, Synthesis, and Anti-Colon Cancer Activity Evaluation
- Source :
- Molecules, Volume 24, Issue 9, Molecules, Vol 24, Iss 9, p 1685 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent and selective COX-2 inhibitors by computer-aided drug analysis of known COX-2 inhibitors. A total of 26 compounds were synthesized and evaluated COX-2 inhibition and pharmacological efficiency both in vitro and in vivo with multi-angle of view. Among them, compound 4b exhibited most excellent anti-proliferation activities against SW620 cells with IC50 of 0.86 &plusmn<br />0.02 &micro<br />M than Celecoxib (IC50 = 1.29 &plusmn<br />0.04 &micro<br />M). The results favored our rational design intention and provides compound 4b as an effective COX-2 inhibitor available for the development of colon tumor therapeutics.
- Subjects :
- Angiogenesis
Molecular Conformation
Pharmaceutical Science
Quantitative Structure-Activity Relationship
Apoptosis
Pharmacology
Analytical Chemistry
Mice
0302 clinical medicine
Drug Discovery
colon tumor therapeutics
dihydropyrazole derivatives
chemistry.chemical_classification
0303 health sciences
Sulfonamides
Molecular Structure
Chemistry
Molecular Docking Simulation
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Colonic Neoplasms
Molecular Medicine
medicine.drug
Antineoplastic Agents
Molecular Dynamics Simulation
pharmacological efficiency
Article
COX-2 inhibitors
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
docking simulation
In vivo
Cell Line, Tumor
sulfonamide
medicine
Cell Adhesion
Animals
Humans
Physical and Theoretical Chemistry
IC50
030304 developmental biology
Cell Proliferation
Cyclooxygenase 2 Inhibitors
Dose-Response Relationship, Drug
Organic Chemistry
Rational design
Xenograft Model Antitumor Assays
In vitro
Sulfonamide
Oxygen
Disease Models, Animal
Enzyme
Drug Design
Celecoxib
Pyrazoles
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....443957fbe29707afaa3bbdb4ac78a896
- Full Text :
- https://doi.org/10.3390/molecules24091685