مشتقات الباربيتورات الجديدة كعوامل نشطة بيولوجياً

New Barbiturate Derivatives as Biological Active Agents

Abstract

This present study included two steps to prepare and characterize ten compounds; the First step was the preparation of [M1] [5-(4-hydroxybenzylidene) pyrimidine-2,4,6(1H,3H,5H)-trione] by reacting barbituric acid with 4-hydroxybenzaldehyde, in the presence of DMSO and ice.
The second step was the preparation of a number of barbiturate derivatives (M2 – M11) by adding a drug containing the carboxyl group (Ciprofloxacin, Ampicillin, Cefotaxime, Cephalexin, Diclofenac sodium, Ceftriaxone, Naproxen, Mefanemic, Ibuprofen and Folic acid). The processes were performed by converting the carboxylic group into chloride-acid group drugs by reacting with SOCl2 and then synthesizing them as a pharmacological derivative reacting with the barbituric derivative M1 in the presence of pyridine and chloroform to produce the final target molecules (M2 -M11).
Antibacterial activity against Gram-positive bacteria (Staphylococcus Aurous) and Gram-negative bacteria (Escherichia Coli). Were studied A number of prepared compounds showed higher areas of inhibition than free drugs against (staphylococcus aureus). The compounds showed higher activity against Gram-negative bacteria, the best inhibition in both cases was compound (M8, Barbiturate derivative with Naproxen), which reached (45mm) in (Staphylococcus Aurous) and (50mm) in (Escherichia Coli).
In addition, the anticancer activity of all compounds towards a breast cancer cell line (MCF7) was studied. It showed a significant inhibition of the growth of breast cancer cells, and a decrease in the growth of cancer cells, which makes it a promising drug for the treatment of breast cancer. The results from the most to the least inhibiting were shown below
M8>M6>M3>M10>M5>M7 >M9 >M2>M4 >M11
Direction of increasing inhibition
The results showed that the compound M8 is the most inhibiting. The resulting compounds were also tested for Molecular Docking and the test was on estrogen receptor alpha protein modulators (PDB id: 6wok). The compound M8 showed the best results.