Eco-friendly synthesis, biological evaluation and QSAR studies of dihydropyrimidinone/thione derivatives

Abstract

Dihydropyrimidinone/thiones (DHPMs) hold earmarked place in the field of natural and synthetic organic chemistry, because of their therapeutic and pharmacological properties. Synthesis of such biologically important compounds assumes great concern. Objectives The aim of the present work was to synthesize structurally challenging DHPMs through green procedure, evaluated for antibacterial activity and to perform QSAR analysis to attain the structural requirements for the antibacterial activity. The synthesis of dihydropyrimidinone/thiones was accomplished via threecomponent one-pot cyclocondensation between substituted alkyl/aryl aldehydes, diketone and urea/thiourea in the presence of pine apple juice at room temperature. The structures of the compounds were established by spectral analysis and evaluated for antibacterial activity. Possible correlation between observed biological activity and physicochemical descriptors was studied. Synthesis of DHPMs by pineapple juice as a catalyst, complies with principle of green chemistry. Moreover, this solvent free approach totally offers nonpolluting environment and avoiding the usage of toxic organic solvents. The spectral analysis reveals that all the compounds 1a-1p was in good agreement with the standard values reported in the literature for these types of structures. The tested compounds 1e, 1m & 1i, 1o showed maximum activity against S. aureus and E. coli at concentrations i.e250 & 500μg /ml respectively. The statistically significant equations with good coefficient of correlation were obtained by correlating antibacterial activities as dependent variables and substituent constants as independent variable. The result of the QSAR study suggested that steric and thermodynamic descriptors contributed significantly to biological activity. Green synthesis of dihydropyrimidinone/thiones is extremely useful and improved procedure for the Biginelli reaction with excellent yields in shorter reaction time with high purity of the products. Through the iterative computational approach, this study could be utilized to design more potent dihydropyrimidinone/thione analogues as antimicrobial agents.