International journal of molecular sciences, 2023-01, Vol.24 (3), p.2648
2023
Details
- Autor(en) / Beteiligte
- Titel
- Discovery of Small Molecule COX-1 and Akt Inhibitors as Anti-NSCLC Agents Endowed with Anti-Inflammatory Action
- Ist Teil von
- International journal of molecular sciences, 2023-01, Vol.24 (3), p.2648
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2023
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- Targeted therapies have come into prominence in the ongoing battle against non-small cell lung cancer (NSCLC) because of the shortcomings of traditional chemotherapy. In this context, indole-based small molecules, which were synthesized efficiently, were subjected to an in vitro colorimetric assay to evaluate their cyclooxygenase (COX) inhibitory profiles. Compounds and were found to be the most selective COX-1 inhibitors in this series with IC values of 8.90 µM and 10.00 µM, respectively. In vitro and in vivo assays were performed to evaluate their anti-NSCLC and anti-inflammatory action, respectively. 2-(1 -Indol-3-yl)- '-(4-morpholinobenzylidene)acetohydrazide ( ) showed selective cytotoxic activity against A549 human lung adenocarcinoma cells through apoptosis induction and Akt inhibition. The in vivo experimental data revealed that compound decreased the serum myeloperoxidase and nitric oxide levels, pointing out its anti-inflammatory action. Moreover, compound diminished the serum aminotransferase (particularly aspartate aminotransferase) levels. Based on the in vitro and in vivo experimental data, compound stands out as a lead anti-NSCLC agent endowed with in vivo anti-inflammatory action, acting as a dual COX-1 and Akt inhibitor.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms24032648Titel-ID: cdi_doaj_primary_oai_doaj_org_article_23db509aa79b425cbd9ab752088d7afb
- Format
- –
- Schlagworte
- Adenocarcinoma, Akt, AKT protein, Angiogenesis Inhibitors - pharmacology, anti-inflammatory action, Anti-Inflammatory Agents - pharmacology, Anti-Inflammatory Agents - therapeutic use, Anti-Inflammatory Agents, Non-Steroidal - pharmacology, Apoptosis, Aspartate aminotransferase, Cancer therapies, Carcinoma, Non-Small-Cell Lung, Cell cycle, Chemotherapy, Colorimetry, COX-1, Cyclooxygenase 1 - metabolism, Cyclooxygenase 2 - metabolism, Cyclooxygenase 2 Inhibitors - pharmacology, Cyclooxygenase 2 Inhibitors - therapeutic use, Cyclooxygenase-1, Cytotoxicity, Disease prevention, FDA approval, Humans, hydrazones, Inflammation, Inhibitors, Kinases, Lung cancer, Lung Neoplasms, Medical prognosis, Metastasis, Molecular Docking Simulation, Molecular Structure, Mortality, Nitric oxide, non-small cell lung cancer, Non-small cell lung carcinoma, Nonsteroidal anti-inflammatory drugs, Pathogenesis, Peroxidase, Proteins, Proto-Oncogene Proteins c-akt, Radiation therapy, Ribonucleotide reductase, Structure-Activity Relationship, thiosemicarbazides, Transaminases, Tumorigenesis