Synthesis, antibacterial studies, and molecular modeling studies of 3,4-dihydropyrimidinone compounds

Abstract

The syntheses of dihydropyrimidinones (DHPMs) using solvent-free grindstone chemistry method. All the synthesized compounds exhibited significant activity against pathogenic bacteria. The current effort has been developed to obtain new DHPM derivatives that focus on the bacterial ribosomal A site RNA as a drug target. Molecular docking simulation analysis was applied to confirm the target specificity of DHPMs. The crystal structure of bacterial 16S rRNA and human 40S rRNA was taken as receptors for docking. Finally, the docking score, binding site interaction analysis revealed that DHPMs exhibit more specificity towards 16S rRNA than known antibiotic amikacin. Accordingly, targeting the bacterial ribosomal A site RNA with potential drug leads promises to overcome the bacterial drug resistance. Even though, anti-neoplastic activities of DHPMs were also predicted through prediction of activity spectra for substances (PASS) tool. Further, the results establish that the DHPMs can serve as perfect leads against bacterial drug resistance.

Synthesis of 4,4-Disubstituted 3,4-Dihydropyrimidin-2(1<i>H</i>)-ones and -thiones, the Corresponding Products of Biginelli Reaction Using Ketone, and Their Antiproliferative Effect on HL-60 Cells

“…These versatile heterocycles show a wide range of biological activities for medicinal applications. [6][7][8][9][10] For example, they display calcium channel inhibition, 11,12) anticancer, 13,14) antibacterial, 15) antifungal, 16) anti-human immunodeficiency virus (HIV), 17) antimalarial, 18) anti-inflammatory, 19) and antioxidation 20) activities. However, this type of reaction has serious synthetic limitations.…”

Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties

“…Ramachandran et al reported the syntheses of dihydropyrimidinones 67 and 68 using solvent-free grindstone chemistry method catalyzed by CuCl 2 ·2H 2 O and HCl ( Scheme 19 ) [ 91 ]. All the synthesized compounds exhibited significant activity against pathogenic bacteria Salmonella typhi and Staphylococcus aureus .…”

Chitosan-silica Sulfate Nano Hybrid: An Efficient Biopolymer Based-heterogeneous Nano Catalyst for Solvent-free Synthesis of 3,4-Dihydropyrimidine-2(1H)-one/thiones

“…4,9 Due to the problems associated with the classical Biginelli reaction such as harsh reaction conditions, low yields, and long reaction times and also regarding to the significance of DHPMs, hence the numerous reaction conditions using various Lewis and Brønsted acid catalysts have been developed so far. 5 To date, a plenty of homogeneous and heterogeneous catalysts such as nano BF 3 •SiO 2 , 10 Bi(III) supported on silica-coated Fe 3 O 4 nanoparticles, 11 TiCl 3 OTf-[bmim]Cl, 12 [TEAPS]H 2 PMo 12 O 40 , 13 CuCl 2 /HCl, 14 sulfated silica tungstic acid, 15 ErCl 3 •6H 2 O, 16 SnCl 2 /nano SiO 2 , 17 L-proline nitrate, 18 D-xylonic acid, 19 Fe(OTs) 3 •6H 2 O, 20 NiCl 2 •6H 2 O/ HCl, 21 Co@imine-Na + -montmorillonite, 22 dendrimer-attached phosphotungstic acid nanoparticles immobilized on nanosilica, 23 Ce(LS) 3 , 24 bentonite/PS-SO 3 H, 25 silica sulfuric acid, 26 HClO 4 •SiO 2 , 27 and the exchanged cations in an Algerian montmorillonite 28 under conventional heating, ultrasound and microwave irradiations as well as solvent-free conditions have been reported to achieve DH-PMs synthesis. 5 Although these protocols are accompa-nied with several advantages; however, they suffer from several defects such as the use of metal-based, corrosive, toxic, expensive, non-reusable, and moisture sensitive catalysts, tedious work-up and purification processes, environmental contaminations, the use of harmful organic solvents, inadequate yields, and also long reaction times.…”