Anticancer profile and anti-inflammatory effect of new N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives
| Autor: | Aida A. El-Azzouny, Rasha M. Hassan, Mohammed S. Abdel-Maksoud, Mohamed Nabil Aboul-Enein, Chang-Hyun Oh |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Stereochemistry
Cell Survival Pyridines Antineoplastic Agents Pyrazole Biochemistry Nitric oxide chemistry.chemical_compound Mice Structure-Activity Relationship Cell Line Tumor Drug Discovery medicine Structure–activity relationship Animals Humans Prostaglandin E2 Molecular Biology IC50 Cell Proliferation Sulfonamides biology Dose-Response Relationship Drug Molecular Structure Kinase Organic Chemistry Anti-Inflammatory Agents Non-Steroidal Nitric oxide synthase RAW 264.7 Cells chemistry Biological target biology.protein Cytokines Pyrazoles Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | Bioorganic chemistry. 117 |
| ISSN: | 1090-2120 |
| Popis: | A new series of N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives 11a-o were designed and synthesized based on our previous works. The new series was tested for its anticancer and anti-inflammatory effects. The anticancer profile of final target compounds was obtained by testing them over 60 cell lines belong to nine types of cancers. Compound 11c showed the highest percent inhibition, so its potency was measured over the most sensitive cell line to determine its IC50 over each cell. In addition, compound 11c was tested over kinase panel to get its biological target(s). Compound 11c had strong activity over JNK1, JNK2, p38a and V600EBRAF. All final target compounds were tested against the four kinases to build a structure activity relationship. Compound 11c was subjected to cell cycle analysis to check at which phase is affected by 11c. The anti-inflammatory effect of final target compounds was screened by testing their ability to inhibit both nitric oxide release and prostaglandin E2 production on raw 264.7 macrophages in addition to test their cytotoxic effect on the same cells. Compound 11n showed the highest ability to inhibit prostaglandin E2 and all compound showed moderate to low activity regarding inhibition of nitric oxide release. Compound 11n was investigated for its ability to reduce Interleukin 6 and TNF-alpha. In addition, compound 11n was tested for its effect on induced Nitric oxide synthase (iNOS), and COX-2 mRNA expression level and its effect on nitric oxide synthase (iNOS), COX-1 and COX-2 protein levels where it showed selectivity for COX-2 compared to COX-1 and iNOS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect