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.

Synthesis and molecular docking of some new 3,5‐bis‐(diazipine, pyrazolopyrimidine, pyrimidine, and pyrazole) pyridine derivatives and their in vitro and in vivo biological evaluation as potential antitumor agents

“…Docking was used to detect the protein's binding modes to the active site of protein. It gives an investigation for the probable mechanism of action of some new compounds with promising biological activity [46]. The three‐dimensional conformations and structures of the enzyme were obtained from the Protein Data Bank (PDB) website.…”

“…Repairing of the structure of the protein was done at first and afterward protonated in presence of ligand using the Protonate 3D in MOE software. Docking process was carried out according to the previously published works [46].…”

Synthetic strategies of heterocycle-integrated pyridopyrimidine scaffolds supported by nano-catalysts

“…Fadda el al . 80 have synthesized a series of pyrido[2,3- d ]pyrimidines by reactions of 6-amino-2-thiouracil with cyanopyridine or enaminonitriles or arylidenes or ethyl 3-chloro-pyridazine-4-carboxylate or 1-(3-chloro-pyridazin-4-yl)ethan-1-one or substituted 4-chloro-pyrimidine-5-carbonitriles in the absence of nano-catalyst. Two compounds from this series e.g.…”

Aminouracil and aminothiouracil as versatile precursors for a variety of heterocyclic systems

“…Compound 77 exhibited potent anti-microbial activity against the Gram-positive Bacillus subtilis (Scheme 32). 106 Ohanjanyan et al 108 reported the synthesis of dihydropyrido [2,3-d]pyrimidin-4(3H)-ones 80a and 80b in 52% and 58% yields, respectively, via a multi-component reaction of 6-aminothiouracil 3 or 6 with aryl aldehydes 21 and pentane-2,4-dione 58 (Scheme 34, Table 15). 87) in ethanol at reflux and in the presence of trimethylamine as a catalyst (Scheme 38, Table 18).…”

“…Synthesis of pyrimido[5′,4′:5,6]pyrido[4,3c]pyridazine. Pyrimido[5′,4′:5,6]pyrido[4,3-c]pyridazines 119a, 119b and 120 were synthesized via reaction of aminothiouracil (6) with chloropyridazines 118a, 118b and 118c in DMF in the presence of piperdine as a catalyst (Scheme 55) 106.…”