Synthesis, Biological Activities and in Silico ADMET Study of Coumarin3,4-Dihydropyrimidin-2(1H)-Ones

Abstract

The synthesis of hybrid molecules represents a promising pathway for the development of new drugs. Dihydropyrimidinones (DHPMs) have demonstrated significant therapeutic and pharmacological properties, particularly as the foundational structure of several calcium channel blockers and antihypertensive agents. A wide range of biological effects, including antiviral, antitumor, antibacterial, and anti-inflammatory activities, have been described for these compounds. Functionalized DHPMs have shown significant activities against bacteria, viruses, and tumors. The synthesis of DHPMs has attracted considerable interest among organic and medicinal chemists. The most common method for synthesizing DHPMs and their corresponding dihydropyrimidinethiones (DHPMTs) involves the multicomponent Biginelli reaction. Several studies have been reported in the literature on the synthesis and biological evaluation of various pyrimido-fused heterocycles, such as pyrimido[4,5-d]pyridazin-8(7H)-ones, pyrano[2,3-d]pyrimidines, pyrido[2,3-d]pyrimidines, and 2,4- diaminopyrido[2,3-d]pyrimidines. As part of our interest in the synthesis of fused heterocycles, and given the importance of hybrid molecules and their synthesis which addresses several drawbacks, we describe in this work a simple strategy for the synthesis of a new series of coumarin-dihydropyrimidinone hybrid molecules. In silico toxicity predictions indicated that these compounds should have good oral bioavailability. The compounds were screened for their antimicrobial activity, and the results showed that compound 5b was the most active against the bacterium Staphylococcus aureus. Additionally, the compounds were docked with the FtsZ protein from S. aureus.