title: Design, Synthesis, In Silico and In Vitro Studies of Substituted 1, 2, 3, 4- Tetrahydro Pyrimidine Phosphorus Derivatives.
abstract: Molecular docking studies of the designed two series (4a-l, 6a-l, 9 and 10) of novel substituted phosphorylated 1, 4-dihydropyridine and 1,2,3,4-tetrahydropyrimidine derivatives against the drug targets of DHFR from Bacillus cereus, LpxC from Pseudomonas aeruginosa, IDH from E. coli and MurB from Staphylococcus aureus were encouraged for their synthesis. These compounds were synthesized from substituted aromatic aldehydes, thiourea/urea and ethyl acetoacetate in the presence of polyphosphoric acid (PPA). These were further phosphorylated with diethyl (2-chloroethoxy) methyl phosphonate to get the desired products. In vitro anti-bacterial activity against the specified bacterial strains related to docked protein exhibited good inhibitory activity at different dose concentrations. Quantitative Structure Activity Relationship (QSAR) descriptors of the designed structures have demonstrated their satisfactory drug like properties. The results from Molecular Docking, QSAR descriptors and in vitro anti-bacterial activities led to the identification of safer and potential antibacterial agents of the title compounds screened. Compounds 4a, 4d, 4i, 6a, 6d, 9 and 10 were found to be potent antibacterial agents.
authors.forename: Kilaru Ravendra
authors.initials: KR
authors.lastname: Babu
authors.forename: Yellapu Nanda
authors.initials: YN
authors.lastname: Kumar
authors.forename: Aminedi
authors.initials: A
authors.lastname: Raghavendra
authors.forename: Venukadasula
authors.initials: V
authors.lastname: Phanindra
authors.forename: Golla
authors.initials: G
authors.lastname: Madhava
authors.forename: Nuchu
authors.initials: N
authors.lastname: Ravi
authors.forename: Matcha
authors.initials: M
authors.lastname: Bhaskar
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India. rajuchamarthi10@gmail.com.
authors.forename: Chamarthi Naga
authors.initials: CN
authors.lastname: Raju
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D015195:Drug Design; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010758:Phosphorus / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011743:Pyrimidines; D010758:Phosphorus