IN SILICO SCREENING OF QUERCETIN ANALOGUES AS POTENTIAL INHIBITORS OF TUMOR NECROSIS FACTOR-ALPHA FOR DIARRHEA MITIGATION IN IRINOTECAN CANCER TREATMENT

Abstract

Diarrhea can be caused due to many reasons in an oncological patient. It could be due to radiation therapy, graft vs host infections, chemotherapeutic agents. Early diagnosis of causative agent can help to prevent diarrhea in cancer patients. Chemotherapeutic agents such as 5 fluorouracil with leucovorin, capecitabine and irinotecan are main causative agent of diarrhea. Loperamide and Octreotide are two recommended treatments for chemotherapy induced diarrhea. Loperamide can only treat grade 1 or 2 diarrhea, it becomes ineffective in severe cases of diarrhea. Octreotide is especially for treating grade 3 or 4 diarrhea but one drawback is that it requires hospitalization for fluid resuscitation due to dehydration in patients which thus increases the cost of treatment. The therapeutic potential of TNF- alpha inhibition for conditions including cancer, diabetes, and particularly autoimmune illnesses is significant. Even though there are several small molecule inhibitors of TNF- that have been discovered, no orally active treatment has yet been revealed that necessitates the urgent need for a small molecule drug against TNF- alpha. This research paper presents a comprehensive analysis of autodocking results obtained from virtual screening experiments conducted on a library of plant natural compound as inhibitor - Quercetin. The objective was to identify potential lead compounds with high binding affinities and favourable binding modes against the Tumor Necrosis Factor – alpha. Our findings reveal promising candidates for further investigation as potential therapeutics in the treatment of chemotherapy induced diarrhoea.