| Autor: |
Gomaa M; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia., Gad W; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh 6860404, Egypt., Hussein D; Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia., Pottoo FH; Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia., Tawfeeq N; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia., Alturki M; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia., Alfahad D; College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia., Alanazi R; College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia., Salama I; Department of Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 8366004, Egypt., Aziz M; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh 6860404, Egypt., Zahra A; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh 6860404, Egypt., Hanafy A; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh 6860404, Egypt. |
| Abstrakt: |
Drug repurposing is a promising approach that has the potential to revolutionize the drug discovery and development process. By leveraging existing drugs, we can bring new treatments to patients more quickly and affordably. Anti-inflammatory drugs have been shown to target multiple pathways involved in cancer development and progression. This suggests that they may be more effective in treating cancer than drugs that target a single pathway. Cell viability was measured using the MTT assay. The expression of genes related to inflammation (TNFa, IL1b, COX-1, COX-2, and 5-LOX) was measured in HepG2, MCF7, and THLE-2 cells using qPCR. The levels of TNFα, IL1b, COX-1, COX-2, and 5-LOX were also measured in these cells using an ELISA kit. An enzyme binding assay revealed that sulfadiazine expressed weaker inhibitory activity against COX-2 (IC 50 = 5.27 μM) in comparison with the COX-2 selective reference inhibitor celecoxib (COX-2 IC 50 = 1.94 μM). However, a more balanced inhibitory effect was revealed for sulfadiazine against the COX/LOX pathway with greater affinity towards 5-LOX (IC 50 = 19.1 μM) versus COX-1 (IC 50 = 18.4 μM) as compared to celecoxib (5-LOX IC 50 = 16.7 μM, and COX-1 IC 50 = 5.9 μM). MTT assays revealed the IC 50 values of 245.69 ± 4.1 µM and 215.68 ± 3.8 µM on HepG2 and MCF7 cell lines, respectively, compared to the standard drug cisplatin (66.92 ± 1.8 µM and 46.83 ± 1.3 µM, respectively). The anti-inflammatory effect of sulfadiazine was also depicted through its effect on the levels of inflammatory markers and inflammation-related genes (TNFα, IL1b, COX-1, COX-2, 5-LOX). Molecular simulation studies revealed key binding interactions that explain the difference in the activity profiles of sulfadiazine compared to celecoxib. The results suggest that sulfadiazine exhibited balanced inhibitory activity against the 5-LOX/COX-1 enzymes compared to the selective COX-2 inhibitor, celecoxib. These findings highlight the potential of sulfadiazine as a potential anticancer agent through balanced inhibitory activity against the COX/LOX pathway and reduction in the expression of inflammatory genes. |
