Preparation of Some 2,5-Dibromo-3,6-Diisoxazolyl-1,4-Benzoquinone Derivatives

Abstract

In the present study a number of α,β-unsaturated carbonyl compounds were prepared followed by cyclization with hydroxylamine hydrochloride to yield the isoxazoles derivatives. These α,β-unsaturated carbonyl compounds were prepared using Claisen Schmidt condensation by the reaction of different substituted aromatic aldehydes with p-aminoacetophenone in NaOH in absolute ethanol at room temperature. The compounds formed i.e (the amino-isoxazoles) were allowed to react with 2,3,5,6-tetrabromo-1,4-Benzoquinone (bromanil) in the ratio of 2:3reaction in presence of sodium acetate and ethanol to give the p-quinones derivatives. On the other hand the p-quinones derivatives were synthesized by the reactionof the bromanil with the p-aminoacetophenone giving the intermediate(2,5-dibromo-3,6-diamino-(p-diacetylphenyl)-1,4-dione. which was reacted with the substituted aromatic aldehydes to yield the α,β-unsaturated carbonyl compounds derivatives ,which was cyclised with hydroxylamine hydrochloride in presence of in ethanolic sodium acetate at room temperature. The reaction progress for the synthesized compounds was checked by (TLC) technique, MP. ,and yield percentage. The structures of synthesized compounds were confirmed by spectroscopic techniques, Infra-red (I.R), Proton Magnetic Resonance, (1HNMR), and Mass spectrum ( MS). In this work the two routes, which were used for the preparation of the target compounds were found to be identical. This show that different quinones can be produced, and can be tested against the fatal diseases like cancer. Quantitive structure- activity relationship (QSAR) study was carried out using ACD/lab and MOE softwares, for developing a correlation between the structural properties of p-quinones derivatives (in which the benzoquinone is basic molecule in its structure), and their anti-cancer activities. From this correlation, new chemical entities were designed, and their biological activities were predicted from their physicochemical IV descriptors using multiple linear regression method. The QSAR models were considered to be good in accordance to acceptable statistical values obtained. (r = 0.932, r 2 = 0.868, RSME = 0.1235, Q2= 0.7623 ,S= 0.146, P value= 0.0001). Molecular Docking was also carried out to find out the binding affinity of target compounds with suitable protein that was obtained from the Protein Data bank (PDB) i.e. (Albumin 4L69) by using (Epotoside) as a reference drug.