Total phenolic contents and antioxidant activities of various solvent extracts from whole wheat and bran

AbstractTwo wheat varieties grown in Upper and Delta Egypt were compared for their total phenolic content and antioxidant activities. Three solvent systems have been used to prepare the antioxidant extracts from whole wheat and its bran fraction. The three solvent systems included 50% acetone (v/v), 70% methanol (v/v) and 70% ethanol (v/v). Antioxidant activities were tested using DPPH radical scavenging activity and total flavonoid content. The results showed that the extraction solvents and wheat varieties significantly altered the total phenolics and antioxidant activity of whole wheat and bran, and 50% acetone is a recommended solvent for extracting phenolic compounds from the tested wheat and bran. Also data indicated that the bran fraction was rich in total phenolic content and high power for radical scavenging activity than whole wheat. These results showed that wheat bran could be considered as a potential source of antioxidant agent. Therefore, durum wheat variety (Beni-suef-3) showed high level of total phenol contact and antioxidant properties in bran fraction than common wheat variety (Gemiza-9). So, whole meal wheat products maximize health benefits and strongly recommended for use in food processing

Synthesis, characterization and antimicrobial activities of some 5-bromouracilmetal ion complexes

Six new complexes, [Mn(Br-U)2(H2O)2]×4H2O (1), [Cd(Br-U)2]×2H2O (2), [Cu(Br-U)2(H2O)2]×2H2O (3), [Co(Br-U)2(H2O)2]×4H2O (4), [Ni(Br-U)2(H2O)2]×4H2O (5) and [Ag(Br-U)(Br-U-H)]×2(H2O) (6)  were prepared by the reaction of 5-bromoouracil with MnCl2·4H2O, CdCl2·2.5H2O, CuSO4·5H2O, (CH3COO)2Co·4H2O, (CH3COO)2Ni·4H2O and AgNO3 respectively. The complexes were characterized by melting point, elemental microanalyses, IR and 1H NMR spectroscopy. The obtained data indicated that the ligand interacted with the metal ions in its mononegatively charged enol form in a bidentate fashion. Thermogravimetric analyses (TGA and DTG) were also carried out. The data obtained agreed well the proposed structures and showed that the complexes were finally decomposed to the corresponding metal or metal oxide. The ligand and its metal-ion complexes were tested for their antimicrobial activities against four bacterial strains (B. subtillis, S. aureus, E. coli and P. aeruginosa) by the agar-well diffusion technique using DMSO as a solvent. The obtained data showed that the complexes were more potent antimicrobial agents than the parent ligand.               KEY WORDS: 5-Bromoouracil–M2+ complexes, IR, Thermal analyses, 1H NMR, Antimicrobial activity Bull. Chem. Soc. Ethiop. 2019, 33(2), 255-268.DOI: https://dx.doi.org/10.4314/bcse.v33i2.

One pot synthesis, antimicrobial and antioxidant activities of fused uracils: pyrimidodiazepines, lumazines, triazolouracil and xanthines

Abstract Background Uracil derivatives have a great attraction because they play an important role in pharmacological activities. Pyrimidodiazepines, lumazines, triazolopyrimidines and xanthines have significant wide spectrum activities including anticancer, antiviral as well as antimicrobial activities. Results A newly synthesized compounds pyrimido[4,5-b][1, 4]diazepines 5a–e, 6a–d, lumazines 7a–d, triazolo[4,5-d]pyrimidine 8 and xanthines 9, 10 was prepared in a good yields. The antimicrobial and antioxidant activities of compounds 5a, 5b, 6a, 6d and 8 exhibited a wide range activity against the pathogenic tested microbes (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, and Saccharomyces cerevisiae). Compound 8 showed activity against the fungus Aspergillus niger. The highest antioxidant activity was noticed for compound 5a. Conclusions A series of novel pyrimido[4,5-b][1, 4]diazepines 5a–e, 6a–d, lumazines 7a–d, triazolo[4,5-d]pyrimidine 8 and xanthines 9, 10 was prepared from 5,6-diamino-1-(2-chlorobenzyl)uracil 3 in good yields. Compounds 5a–e, 6a–d were prepared by sequential manipulation of 3 with α,β-unsaturated ketones. Lumazines 7a–d were obtained from 3 by treatment with phenacyl bromides in the presence of TEA. Compound 8 was prepared by treatment of 3 with HNO2, while xanthines 9, 10 were obtained from 3 by consecutive acetylation then intramolecular cyclodehydration or heating with malononitrile under solvent-free condition. The antimicrobial and antioxidant activity of this series was evaluated in vitro and they showed either weak or moderate activities. Graphical abstract Several pyrimido[4,5-b][1,4]diazepines, lumazines, triazolo-, and imidazolopyrimidines were synthesized from the starting compound 4,5-diaminouracils. The newly synthesized compounds were screened for both antimicrobial and antioxidant activities

Synthesis, In Silico Prediction and In Vitro Evaluation of Antimicrobial Activity, DFT Calculation and Theoretical Investigation of Novel Xanthines and Uracil Containing Imidazolone Derivatives

Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives 2a-c as a key intermediate. The corresponding xanthine 3-5 and imidazolone derivatives 6-13 were obtained via reaction of oxazolone derivative 2a-c with 5,6-diaminouracils 1a-e under various conditions. Xanthine compounds 3-5 were obtained by cyclocondensation of 5,6-diaminouracils 1a-c with different oxazolones in glacial acetic acid. Moreover, 5,6-diaminouracils 1a-e were reacted with oxazolones 2a-c in presence of drops of acetic acid under fused condition yielding the imidazolone derivatives 6-13. Furthermore, Schiff base of compounds 14-16 were obtained by condensing 5,6-diaminouracils 1a,b,e with 4-dimethylaminobenzaldehyde in acetic acid. The structural identity of the resulting compounds was resolved by IR, 1H-, 13C-NMR and Mass spectral analyses. The novel synthesized compounds were screened for their antifungal and antibacterial activities. Compounds 3, 6, 13 and 16 displayed the highest activity against Escherichia coli as revealed from the IC50 values (1.8–1.9 µg/mL). The compound 16 displayed a significant antifungal activity against Candia albicans (0.82 µg/mL), Aspergillus flavus (1.2 µg/mL) comparing to authentic antibiotics. From the TEM microgram, the compounds 3, 12, 13 and 16 exhibited a strong deformation to the cellular entities, by interfering with the cell membrane components, causing cytosol leakage, cellular shrinkage and irregularity to the cell shape. In addition, docking study for the most promising antimicrobial tested compounds depicted high binding affinity against acyl carrier protein domain from a fungal type I polyketide synthase (ACP), and Baumannii penicillin- binding protein (PBP). Moreover, compound 12 showed high drug- likeness, and excellent pharmacokinetics, which needs to be in focus for further antimicrobial drug development. The most promising antimicrobial compounds underwent theoretical investigation using DFT calculation

Novel Aminopyrimidine-2,4-diones, 2-Thiopyrimidine-4-ones, and 6-Arylpteridines as Dual-Target Inhibitors of BRD4/PLK1: Design, Synthesis, Cytotoxicity, and Computational Studies

Structural-based drug design and solvent-free synthesis were combined to obtain three novel series of 5-arylethylidene-aminopyrimidine-2,4-diones (4, 5a–c, 6a,b), 5-arylethylidene-amino-2-thiopyrimidine-4-ones (7,8), and 6-arylpteridines (9,10) as dual BRD4 and PLK1 inhibitors. MTT assays of synthesized compounds against breast (MDA-MB-231), colorectal (HT-29), and renal (U-937) cancer cells showed excellent-to-good cytotoxic activity, compared to Methotrexate; MDA-MB-231 were the most sensitive cancer cells. The most active compounds were tested against normal Vero cells. Compounds 4 and 7 significantly inhibited BRD4 and PLK1, with IC50 values of 0.029, 0.042 µM, and 0.094, 0.02 µM, respectively, which are nearly comparable to volasertib (IC50 = 0.017 and 0.025 µM). Compound 7 triggered apoptosis and halted cell growth at the G2/M phase, similarly to volasertib. It also upregulated the BAX and caspase-3 markers while downregulating the Bcl-2 gene. Finally, active compounds fitted the volasertib binding site at BRD4 and PLK1 and showed ideal drug-like properties and pharmacokinetics, making them promising anticancer candidates

Novel pyrimidine Schiff bases and their selenium-containing nanoparticles as dual inhibitors of CDK1 and tubulin polymerase: design, synthesis, anti-proliferative evaluation, and molecular modelling

AbstractNanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases (4–9) were employed in the synthesis of selenium nanoparticle forms (4NPs–9NPs). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity. Compound 4 showed effective anti-proliferative activity against MCF-7(IC50 3.14 ± 0.04 µM), HepG-2(IC50 1.07 ± 0.03 µM), and A549(IC50 1.53 ± 0.01 µM) cell lines, while its selenium nanoform 4NPs showed excellent inhibitory effects, with efficacy increased by 96.52%, 96.45%, and 93.86%, respectively. Additionally, 4NPs outperformed 4 in selectivity against the Vero cell line by 4.5-fold. Furthermore, 4NPs exhibited strong inhibition of CDK1(IC50 0.47 ± 0.3 µM) and tubulin polymerase(IC50 0.61 ± 0.04 µM), outperforming 4 and being comparable to roscovitine (IC50 0.27 ± 0.03 µM) and combretastatin-A4(IC50 0.25 ± 0.01 µM), respectively. Moreover, both 4 and 4NPs arrested the cell cycle at G0/G1 phase and significantly forced the cells towards apoptosis. Molecular docking demonstrated that 4 and 4NPs were able to inhibit CDK1 and tubulin polymerase binding sites

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

A series of quinoline–uracil hybrids (10a–l) has been rationalized and synthesized. The inhibitory activity against hCA isoforms I, II, IX, and XII was explored. Compounds 10a–l demonstrated powerful inhibitory activity against all tested hCA isoforms. Compound 10h displayed the best selectivity profile with good activity. Compound 10d displayed the best activity profile with minimal selectivity. Compound 10l emerged as the best congener considering both activity (IC50 = 140 and 190 nM for hCA IX and hCA XII, respectively) and selectivity (S.I. = 13.20 and 9.75 for II/IX, and II/XII, respectively). The most active hybrids were assayed for antiproliferative and pro-apoptotic activities against MCF-7 and A549. In silico studies, molecular docking, physicochemical parameters, and ADMET analysis were performed to explain the acquired CA inhibitory action of all hybrids. A study of the structure–activity relationship revealed that bulky substituents at uracil N-1 were unfavored for activity while substituted quinoline and thiouracil were effective for selectivity