Hybrids of Pyrimidine and Curcumin: Synthesis, DFT Calculations, Molecular Docking Studies and Biological Evaluation for Antibacterial and Antioxidant Activity
摘要
A series of new (E,E)-4,6-bis(4-substituted-styryl)-pyrimidines (6a-d) were synthesized in moderate to good yields (45–83%) and characterized by using UV, FT-IR, 1H, 13C NMR, and mass spectrometry. The B3LYP/6-31G(d,p) level was used for density functional theory (DFT) investigations of compounds 6a-d to compare the optimized geometries, spectroscopic data and vibrational frequencies, and for understanding structural characteristics by global and local reactivity descriptors, MESP, NLO and NBO analysis, and AIM approach. The resultant hybrids 6a-d were in-vitro screened for antibacterial activity against pathogenic and non-pathogenic bacterial strains using ampicillin and gentamycin as reference drugs. Among all, compound 6a exhibited the best antibacterial activity against E. coli and P. aeruginosa with an inhibition zone of 21 mm and 20 mm respectively. Further, the DPPH radical scavenging activity analysis was used to examine the antioxidant potential of these hybrids at different doses (10–250 µg/mL) and it has been found that all the compounds exhibited greater scavenging activities in comparison to the standard compound BHT (butylated hydroxytoluene). The in-silico molecular docking studies were also performed against the enzyme Lipid A (LpxH) to understand the antibacterial mechanism associated with inhibitors 6a-d. The more negative binding energies of compounds 6a-d in comparison to reference drugs ampicillin and gentamycin clearly indicates the more thermodynamically favorable and tightly bound interactions. Hence, these new hybrids 6a-d may serve as potentially effective inhibitors for developing new antibiotics.