IN-SILICO SCREENING OF COMPOUNDS FOR COLON CANCER (DRUG REPURPOSING)

Colon cancer ranks as the fourth leading cause of cancer-related deaths worldwide. The epidermal growth factor receptor family of tyrosine kinases (ErbBs) plays a crucial role in regulating cell proliferation, survival, differentiation, and migration. Tyrosine kinase, an enzyme within the EGFR family, may exhibit heightened activity or elevated levels in certain cancer cells; blocking these enzymes can help inhibit cancer cell growth. This inhibition can be achieved through the use of tyrosine kinase inhibitors (TKIs), whichcompete with ATP for the ATP binding site on protein tyrosine kinases (PTK). By reducing tyrosine kinase phosphorylation, TKIs effectively impede cancer cell proliferation. Pyrimidines serve as vital pharmacophores in the medicinal landscape, boasting a wide array of biological properties, including anticonvulsant, analgesic, sedative, antidepressant, antipyretic, anti-inflammatory, antiviral, anti-HIV, and antimicrobial activities. In drug discovery, drug repurposing involves investigating already approved drug candidates for the potential treatment of various other diseases. Numerous marketable drugs containing a pyrimidine ring are utilized in the treatment of different cancers, such as breast cancer, myeloid leukemia, pancreatic cancer, and liver cancer. In our present study, we selected 21 FDA approved drugs containing a pyrimidine moiety, which are currently applied to treat various diseases. Molecular docking was conducted using AutoDock Software on PDB ID 1M17. Out of 21 compounds analyzed, 13 exhibited binding energies ranging from (-8.0) to (-9.3) kcal/mol, with Erlotinib showing a binding energy of (-7.8) kcal/mol. Based on these findings, the drugs evaluated in this study may serve as lead compounds for the development of more potent tyrosine kinase inhibitors aimed at curbing the progression of colon cancer.