title: Nanoformulation and antimicrobial evaluation of newly synthesized thiouracil derivatives.
abstract: The present work reports the synthesis of a new series of pyridopyrimidine derivatives. The newly synthesized compounds were characterized by various analytical and spectral techniques. In addition, their antimicrobial activity was evaluated as well as modeling studies were performed to investigate their ability to recognize and bind to the biotin carboxylase (BC)-active site. The results showed a broad spectrum antibacterial and antifungal profile of the synthesized derivatives. Docking results demonstrated that all members of this class of new derivatives were able to recognize the active site of Escherichia coli BC and form different types of bonding interactions with key active site amino acid residues. Besides the compounds with promising antimicrobial activity in addition to 6-aminothiouracil, as control, were incorporated into polycaprolactone nanoparticles to improve their water solubility, permeability through physiological barriers and consequently enhanced therapeutic efficacy. The compounds-loaded nanoparticles were prepared using single emulsion-solvent evaporation technique, and their diameters were found to be in the range 136 ± 30 to 213 ± 28 nm. Transmission electron microscopy (TEM) showed a spherical and dense morphology of the nanoparticles. The results also showed high entrapment efficiency of the synthesized bioactive compounds in the nanoparticles (85 ± 5% to 91 ± 2%) with a desirable in vitro biodegradation and release profiles.
authors.affiliation: a Chemistry Department , Faculty of Science, Mansoura University , Mansoura , ET , Egypt ;
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Fadda
authors.affiliation: b Chemistry Department , Faculty of Oral and Dental Medicine, Delta University for Science and Technology , Gamasa , Egypt ;
authors.forename: Nesma M
authors.initials: NM
authors.lastname: Bayoumy
authors.affiliation: c Zewail City of Science and Technology , 6th October City , Giza , Egypt.
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Sherbiny
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry; D055808:Drug Discovery / Q000379:methods*; D065546:Drug Liberation; D004926:Escherichia coli / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D011485:Protein Binding; D013499:Surface Properties; D013889:Thiouracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013889:Thiouracil; D019731:Carbon-Nitrogen Ligases; C019791:biotin carboxylase
keywords: 6-aminothiouracil; Antimicrobial; docking; nanoparticles; polycaprolactone; pyridopyrimidine