COMPARATIVE ANALYSIS OF DIFFERENT CURCUMIN ANALOGUES TO INHIBIT TLR4 EXPRESSION IN BREAST CANCER- AN IN-SILICO STUDY

Abstract

Chronic inflammation is closely related to the emergence of a number of cancers, including Breast cancer. Inflammation causes damage to the cell’s DNA which leads to its abnormal growth and formation of tumor mass. One of the most commonly known receptor responsible for inflammatory reactions is Toll-like receptor 4 (TLR4). It is activated majorly by bacterial LPS. Its activation further activates Cyclooxygenase enzyme that catalyzes the conversion of arachidonic acid into prostaglandins that lead to inflammation-like conditions. COX2 has also been correlated to the promotion of tumor growth. It enhances metastasis, neoplasia, lymphangiogenesis, etc., and is also related to poor prognosis in the breast cancer patients. Curcumin derived from turmeric is a proven inhibitor of COX2. In my project I have aimed to analyse and compare the inhibitory properties of other analogues of curcumin that have previously been known to inhibit COX2. The experimental layout began with screening the molecules on the basis of drug-likeness using Lipinski rule of five. The suitable ligand molecules were further subjected to other experiments, i.e., ligand docking and drug potential assessment. After all the experiments, out of the five selected Curcumin analogues, Isoeugenol (extracted from clove) was determined as the best fit molecule. The druglikeliness and drug potential assessment results further validate its use as a potential inhibitor and can further be tested for in-vivo efficacy. This drug can further be used in the 1st line therapy of locally advanced and metastatic breast cancer patients as it will inhibit COX2 that promotes metastasis of cancer cells. Isoeugenol extracted from Eugenia caryophyllus (Cloves) can further be proven as a better COX2 inhibitor than its chemical counterparts, as it is a natural compound and will therefore have significantly less side effects.