A one-pot multicomponent facile synthesis of dihydropyrimidin-2(1)-thione derivatives using triphenylgermane as a catalyst and its binding pattern validation

• Published in: RSC advances 2016-01, Vol.6 (83), p.79651-79661
• Main Authors: Andleeb, Sohaila, Imtiaz-ud-Din, Rauf, Muhammad Khawar, Azam, Syed Sikander, Badshah, Amin, Sadaf, Haseeba, Raheel, Ahmed, Tahir, Muhammad Nawaz, Raza, Saad
• Format: Article
• Language: English
• Subjects: Binding; Catalysts; Derivatives; Docking; Enzymes; Inhibitors; Molecular dynamics; Reaction time
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c6ra19162b

A series of substituted dihydropyrimidin-2(1 H )-thione derivatives ( 1-8 ) have been synthesized using a facile and modified procedure with triphenylgermyl propionate as a catalyst. In comparison with the classical Biginelli reaction, this new protocol has the advantages of excellent yield and shorter reaction times. The synthesized compounds have been characterized by various spectroscopic techniques such as FT-IR, multinuclear ( 1 H/ 13 C) NMR spectroscopy and single crystal XRD analysis. Molecular docking studies were performed to identify the probable binding modes of potent inhibitors in the active site of the enzymes human topoisomerase II alpha ( 4FM9 ) and Helicobacter pylori urease ( 1E9Y ). Compound 3 was found to be the most potent inhibitor according to the molecular docking scores and molecular dynamic simulations which suggests it can be further processed as a lead molecule to interpret the pharmacological properties of these compounds. A series of substituted dihydropyrimidin-2(1 H )-thione derivatives ( 1-8 ) have been synthesized and docked against enzymes human topoisomerase II alpha ( 4FM9 ) and Helicobacter pylori urease ( 1E9Y ) for binding mode validation.