Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
Browse
2 results
Search Results
Article A Small Indole Derivative Isolated From Caper (Capparis Ovata) as an Inducer of P53-Mediated Apoptosis in Prostate Cancer: Comprehensive In Vitro and In Silico Studies(Wiley, 2025-12-31) Acar, Ozden Ozgun; Gazioglu, Isil; Oruc, Hatice; Kale, Elif; Senol, Halil; Topcu, Gulacti; Sen, AlaattinNatural products with stunning chemical diversity have been extensively researched for their anticancer potential for more than fifty years. This study aimed to determine the effect of indole derivative 1H-indole-2-hydroxy-3-carboxylic acid (IHCA), isolated as a novel alkaloid from Capparis ovata, on selected tumor suppressor, apoptotic, and cell cycle regulatory genes, which are known to be important in cancer pathophysiology, on Caco-2 and LNCaP cells in comparison with Taxol. The molecular mechanism of IHCA's anticancer activity is essentially undefined. Different concentrations of IHCA increased the expression levels of apoptosis-related genes, including BCL-2 and TNF-alpha. In addition, the tumor suppressor genes PTEN, P53, and RB were increased in LNCaP and Caco-2 cells. KRAS, an oncogenic gene, was significantly downregulated by IHCA in LNCaP cells. Western blot results showed that the protein expression levels of P53 and PTEN in LNCaP cells were increased when treated with IHCA, whereas CDK4 and TNF-alpha were decreased. Finally, IHCA and doxorubicin significantly increased P53-driven luciferase activity compared to the control. The results strongly suggest that the novel natural compound IHCA has an anticancer effect involving the regulation of the P53 gene and its networks in vitro. The molecular docking and MD simulation analyses reveal that IHCA exhibits superior binding potential to the MDM2 protein compared to Nutlin-3a. MD simulations further confirm that IHCA maintains a more stable and consistent interaction with MDM2, as indicated by lower RMSD values and reduced ligand fluctuation. These results highlight IHCA's potential as a more effective MDM2 inhibitor, suggesting its promise as a lead compound for anticancer drug development.Clinical Trial Registration: Not applicable.Article Citation - WoS: 33Citation - Scopus: 37In Silico Evaluation of Food-Derived Carotenoids Against SARS-CoV Drug Targets: Crocin Is a Promising Dietary Supplement Candidate for COVID-19(Wiley, 2022-05-11) Mujwar, Somdutt; Sun, Lei; Fidan, OzkanThe current COVID-19 pandemic is severely threatening public healthcare systems around the globe. Some supporting therapies such as remdesivir, favipiravir, and ivermectin are still under the process of a clinical trial, it is thus urgent to find alternative treatment and prevention options for SARS-CoV-2. In this regard, although many natural products have been tested and/or suggested for the treatment and prophylaxis of COVID-19, carotenoids as an important class of natural products were underexplored. The dietary supplementation of some carotenoids was already suggested to be potentially effective in the treatment of COVID-19 due to their strong antioxidant properties. In this study, we performed an in silico screening of common food-derived carotenoids against druggable target proteins of SARS-CoV-2 including main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase. Molecular docking results revealed that some of the carotenoids had low binding energies toward multiple receptors. Particularly, crocin had the strongest binding affinity (-10.5 kcal/mol) toward the replication complex of SARS-CoV-2 and indeed possessed quite low binding energy scores for other targets as well. The stability of crocin in the corresponding receptors was confirmed by molecular dynamics simulations. Our study, therefore, suggests that carotenoids, especially crocin, can be considered an effective alternative therapeutics and a dietary supplement candidate for the prophylaxis and treatment of SARS-CoV-2. Practical applications In this study, food-derived carotenoids as dietary supplements have the potential to be used for the prophylaxis and/or treatment of SARS-CoV-2. Using in silico techniques, we aimed at discovering food-derived carotenoids with inhibitory effects against multiple druggable sites of SARS-CoV-2. Molecular docking experiments against main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase resulted in a few carotenoids with multitarget inhibitory effects. Particularly, crocin as one of the main components of saffron exhibited strong binding affinities to the multiple drug targets including main protease, helicase, replication complex, mutant spike protein of lineage B.1.351, and ADP-ribose phosphatase. The stability of the crocin complexed with these drug targets was further confirmed through molecular dynamics simulations. Overall, our study provides the preliminary data for the potential use of food-derived carotenoids, particularly crocin, as dietary supplements in the prevention and treatment of COVID-19.