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 exhibited most excellent anti-proliferation activities against SW620 cells with IC of 0.86 ± 0.02 µM than Celecoxib (IC = 1.29 ± 0.04 µM). The results favored our rational design intention and provides compound as an effective COX-2 inhibitor available for the development of colon tumor therapeutics.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539903 | PMC |
| http://dx.doi.org/10.3390/molecules24091685 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chiral Aldehyde/Palladium Catalysis Enables Asymmetric Branched-Selective Ring-Opening Functionalization of Methylenecyclopropanes with Amino Acid Esters.
J Am Chem Soc
January 2025
Key Laboratory of Applied Chemistry of Chongqing Municipality and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
Achieving catalytic asymmetric functionalization of methylenecyclopropanes (MCPs) by selective C-C bond cleavage is a notable challenge due to the intricate reaction partners involved. In this work, we report that chiral aldehyde/palladium combined catalysis enables the asymmetric functionalization of MCPs with NH-unprotected amino acid esters. This reaction proceeds through a regiospecific branched ring-opening mechanism, resulting in optically active α,α-disubstituted α-amino acid esters bearing nonconjugated terminal alkene units.
View Article and Find Full Text PDFMW-19, a dihydropyrazole derivative, induces human triple-negative breast cancer cell apoptosis by targeting apoptosis-related pathways.
Chem Biol Drug Des
July 2024
School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China.
Previous studies have indicated that heterocyclic substituted dihydropyrazole derivatives, particularly MW-19, potentially exert anticancer activity in vitro; however, the underlying mechanism remains unknown. The present study was designed to investigate the mechanisms underlying MW-19 activity in triple-negative breast cancer cells. A sulforhodamine B assay was performed to evaluate cell proliferation inhibition rates, and the antitumor effect of MW-19 was evaluated in mice with HCC-1806 xenografts.
View Article and Find Full Text PDFDesign, synthesis and molecular modeling of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives as anti-inflammatory agents by inhibition of COX-2/iNOS production and down-regulation of NF-κB/MAPKs in LPS-induced RAW264.7 macrophage cells.
Eur J Med Chem
June 2024
Department of Pharmacy, The Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address:
Article Synopsis
- 4,5-dihydropyrazole and thiazole derivatives show significant anti-inflammatory properties, motivating researchers to create new steroid-based compounds.
- A specific compound, 12e, demonstrated the strongest anti-inflammatory effects by reducing key inflammatory markers and inhibiting essential enzymes in macrophage cells.
- Further analysis revealed that compound 12e effectively blocked signaling pathways linked to inflammation, with promising results from molecular docking studies suggesting its potential as a treatment for inflammatory diseases.
Design, synthesis and molecular docking of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazole derivatives that act as iNOS/COX-2 inhibitors with potent anti-inflammatory activity against LPS-induced RAW264.7 macrophage cells.
J Steroid Biochem Mol Biol
June 2024
Department of Pharmacy, The Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address:
Inflammation, an important biological protective response to tissue damage or microbial invasion, is considered to be an alarming signal for the progress of varied biological complications. Based on the previous reports in the literature that proved the noticeable efficacy of pyrazole and thiazole scaffold as well as nitrogen heterocyclic based compounds against acute and chronic inflammatory disease, a new set of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazole derivatives were synthesized and evaluated their anti-inflammatory activities in vitro. Preliminary structure-activity relationship (SAR) analysis was conducted by their inhibitory activities against nitric oxide (NO) release in lipopolysaccharide (LPS)-induced RAW 264.
View Article and Find Full Text PDFElectronic and steric substituent effects on the fluorescence emission of 2-pyrazoline derivatives.
Luminescence
November 2023
Department of Chemistry, University of Isfahan, Isfahan, Iran.
A series of substituted 2-pyrazolines were synthesized, and the steric and electronic effects of substituents on the C - and C -positions of the heterocyclic ring on their fluorescent ability were investigated. Two different conjugative intramolecular charge transfer (ICT) and intramolecular charge transfer through space (spiro-conjugation) affect the fluorescence intensity of these compounds. The extent of the ICT process and spiro-conjugation depends on the electronic nature of the additional substitution and its position on the attached aryl rings.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!