Abstract

PYRIMIDINE DERIVATIVES TARGET CANCER THROUGH INHIBITION OF BRD4 EXPRESSION - RESEARCH ARTICLE

Kamrudeen Samani*, Uday Raj Sharma, Giles D., Abhishek Raj Joshi, Aditi Upadhyay, Surendra V., Manjunatha P.M.

Abstract

Series of novel pyrimidine derivatives compound were designed with the help of chemsketch for its anti-cancer activity against bromodomain containing protein (BRD4) and protein was downloaded from protein data bank with PDB code 4HY3 using Accelrys drug discovery studio 3.5. among them The compound 2C possess good CDOCKER Interaction energy, the compound 2c was further synthesized and confirmed by the both physical data as well as spectral data analysis such TLC, Melting Point and IR, 1H NMR, Mass spectroscopy,. The Cytotoxic activity of compound 2C was assessed by MTT assay on various cancer cell line such as HL-60, Hela, MCF- 7, A431 and HCT-116A. Acute toxicity was carried out based on OECD guideline 425, for Invivo model, therapeutic efficacy of compound 2c was evaluated against induced Ehrlich ascites carcinoma (EAC) cancer cell in Swiss albino mice. The animals were divided into 3 group, each group contain eight mice, Group I served as cancer control (0.9 % saline), Group II treated with 5 fluorouracil (20 mg/kg/p.o) can serve as a standard group, Group III treated with synthesized pyrimidine compound (200 mg/kg/p.o), All groups animals were induced with Ehrlich Ascites Carcinoma by injecting 1×106 cells/ml/mouse (i.p) as well as therapy was provided orally once day for 10th days and after post therapy, liver as well as kidney was isolated and antioxidant parameter was estimated, blood was withdrawn from the mice via retro orbital for haematological investigations. The set of three groups containing two mice in each group was observed for the body weight analysis and life expectancy.

Keywords: Antioxidant, Bromodomain, Catalase, Ehrlich Ascites Carcinoma, Pyrimidine.