Synthesis and Biological Evaluation of Some New 3-Aryl-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones and 3-Aryl-2-(benzylthio)quinazolin-4(3H)-ones as Antioxidants; COX-2, LDHA, α-Glucosidase and α-Amylase Inhibitors; and Anti-Colon Carcinoma and Apoptosis-Inducing Agents.

Oxidative stress, COX-2, LDHA and hyperglycemia are interlinked contributing pathways in the etiology, progression and metastasis of colon cancer. Additionally, dysregulated apoptosis in cells with genetic alternations leads to their progression in malignant transformation. Therefore, quinazolinones 3a-3h and 5a-5h were synthesized and evaluated as antioxidants, enzymes inhibitors and cytotoxic agents against LoVo and HCT-116 cells. Moreover, the most active cytotoxic derivatives were evaluated as apoptosis inducers. The results indicated that 3a, 3g and 5a were efficiently scavenged DPPH radicals with lowered IC50 values (mM) ranging from 0.165 ± 0.0057 to 0.191 ± 0.0099, as compared to 0.245 ± 0.0257 by BHT. Derivatives 3h, 5a and 5h were recognized as more potent dual inhibitors than quercetin against α-amylase and α-glucosidase, in addition to 3a, 3c, 3f and 5b-5f against α-amylase. Although none of the compounds demonstrated a higher efficiency than the reference inhibitors against COX-2 and LDHA, 3a and 3g were identified as the most active derivatives. Molecular docking studies were used to elucidate the binding affinities and binding interactions between the inhibitors and their target proteins. Compounds 3a and 3f showed cytotoxic activities, with IC50 values (µM) of 294.32 ± 8.41 and 383.5 ± 8.99 (LoVo), as well as 298.05 ± 13.26 and 323.59 ± 3.00 (HCT-116). The cytotoxicity mechanism of 3a and 3f could be attributed to the modulation of apoptosis regulators (Bax and Bcl-2), the activation of intrinsic and extrinsic apoptosis pathways via the upregulation of initiator caspases-8 and -9 as well as executioner caspase-3, and the arrest of LoVo and HCT-116 cell cycles in the G2/M and G1 phases, respectively. Lastly, the physicochemical, medicinal chemistry and ADMET properties of all compounds were predicted.

Comparison of Phytochemical Composition, Antibacterial, and Antifungal Activities of Extracts from Three Organs of Pistacia lentiscus from Saudi Arabia.

This in vitro study focused on the antimicrobial activity of methanolic and aqueous extracts of three organs (stems, roots, and leaves) of Pistacia lentiscus against nine bacterial species, two fungal, and one yeast strain. A comparative study of the yield, high-performance liquid chromatography (HPLC) composition, and polyphenol content of the different extracts was conducted. The obtained data showed that the yield of the methanolic extracts (between 13% and 33.3%) was greater than that of the aqueous extracts (between 10% and 18%). The highest yield recorded was in the presence of the methanolic leaf extract, followed by the stem and root extracts. Methanolic extracts are richer in polyphenols than aqueous extracts. Indeed, the highest content was observed in the leaf methanolic extract (28.4 mg GAE/g), followed by the stem (2.96 mg GAE/g), and then the root (2.62 mg GAE/g). HPLC revealed variability in the chemical compositions of the different methanolic extracts. The leaf extract was richer in phenolic acids and flavonoids than the stem and root extracts. Regarding antimicrobial activity, it was concluded that the different methanolic extracts of lentisk were more active than the aqueous extracts. In addition, the different methanolic extracts exhibited antimicrobial activity against all tested strains, despite their morphology and Gram-staining. Indeed, the maximum inhibition zones and the minimum inhibitory concentrations for the bacterial strains sensitive to the different methanolic extracts of the mastic tree were in the range of 7 to 11 mm and 12.5 to 25 µg/mL, respectively. In addition, these extracts showed greater inhibitory activity against the tested fungal strains (A. niger and A. flavus) and yeast (C. albicans) than against the bacterial strains. These extracts can be used to treat antimicrobial infections and as food preservatives.

Mesoporous Silica Modified with 2-Phenylimidazo[1,2-a] pyridine-3-carbaldehyde as an Effective Adsorbent for Cu(II) from Aqueous Solutions: A Combined Experimental and Theoretical Study.

In this study, we will present an efficient and selective adsorbent for the removal of Cu(II) ions from aqueous solutions. The silica-based adsorbent is functionalized by 2-phenylimidazo[1,2-a] pyridine-3-carbaldehyde (SiN-imd-py) and the characterization was carried out by applying various techniques including FT-IR, SEM, TGA and elemental analysis. The SiN-imd-py adsorbent shows a good selectivity and high adsorption capacity towards Cu(II) and reached 100 mg/g at pH = 6 and T = 25 °C. This adsorption capacity is important compared to other similar adsorbents which are currently published. The adsorption mechanism, thermodynamics, reusability and the effect of different experimental conditions, such as contact time, pH and temperature, on the adsorption process, were also investigated. In addition, a theoretical study was carried out to understand the adsorption mechanism and the active sites of the adsorbent, as well as the stability of the complex formed and the nature of the bonds.

Biological Evaluation, Molecular Docking Analyses, and ADME Profiling of Certain New Quinazolinones as Anti-colorectal Agents.

Colorectal carcinogenesis is a complex process, which is linked to dysregulation of human secretory phospholipases A2 (hsPLA2-G-IIA, hsPLA2-G-V, and hsPLA2-G-X), proteases (cathepsin-B, collagenase, thrombin, elastase, and trypsin), carbohydrate hydrolyzing enzymes (α-amylase and α-glucosidase), and free radical generating enzyme (xanthine oxidoreductase (XOR)). Therefore, some new quinazolinones were synthesized and evaluated as inhibitors against this array of enzymes as well as cytotoxic agents on LoVo and HCT-116 cells of colorectal cancer. Compounds 3g, 10, 8, 3c, and 1c exhibited promising cytotoxic effects with IC50 values ranging from 206.07 to 459.79 µM. Nine compounds showed promising enzymatic inhibitory effects, 3b, 3d, 3f, 5, 1a, and 12 (α-amylase), 8 (thrombin, elastase and trypsin), 10 (hsPLA2-G-IIA and hsPLA2-G-V), and 3f (α-glucosidase and XOR). Therefore, the most active inhibitors, were subjected to validated molecular docking studies to identify their affinities and binding modes. The expected physicochemical and pharmacokinetic features of the active candidates, 1a, 1c, 3b, 3c, 3d, 3f, 3g, 5, 8, 10, and 12 were predicted using bioavailability radar charts and boiled-egg graphical representations along with the Lipinski rule of five filter. Collectively, these studies showed the significance of derivatives 1c, 3b, 3c, 3d, 8, 10, and 12 as lead scaffolds for further optimization to develop enzymes inhibitors and anti-colorectal agents.

Highly Efficient Electrocarboxylation Method to Synthesize Novel Acid Derivatives of 1,4-Dihydropyridines and to Study Their Antimicrobial Activity.

1,4-Dihydropyridines (1,4-DHPs) hold a top-notch position in the pharmaceutical world due to a broader spectrum of applications, whereas the carboxylic moiety has been an integral part of the physiological world, effective food preservatives, and antimicrobial agents. Seeking the enormous potential and applications of these two classes, we worked to combine these to synthesize 2,2'-[3,5-bis(ethoxycarbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl]diacetic acid the novel dicarboxylic derivatives of 1,4-DHP (9a-k) achieved via the electro-carboxylation of tetrasubstituted-1,4-dihydropyridines (8a-k) derivatives using Mg-Pt electrodes in an undivided cell. The targeted compounds were established by 1H, 13C NMR, IR, and ESI-MS. Further, the synthesized compounds show excellent resistance against various microbes and the activity increased 2-3 folds after the introduction of acid groups. Compound 9b (against E. coli, S. aureus, B. subtilis, A. niger, and P. glabrum), 9d (against E. coli, K. pneumonia, S. aureus, A. janus, and F. oxysporum), 9f (against E. coli and P. fluorescens), and 9k (against F. oxysporum and P. glabrum) were found to be highly active at 4 µg/mL with reference to standard amoxicillin and fluconazole. Further, the present synthetic protocol would open new gates for other researchers to develop new molecules by bioisosteres of these substrates.

Phosphonium-based Ionic Liquid Modified Activated Carbon from Mixed Recyclable Waste for Mercury(II) Uptake.

The contamination of water surfaces by mercury is a dangerous environmental problem due to its toxicity, which leads kidney damage. Activated carbon from mixed recyclable waste modified by phosphonium-based ionic liquid (IL-ACMRW) was therefore prepared and evaluated for Hg(II) remediation. The activated carbon used in this study was prepared from mixed waste, including cardboard, papers and palm wastes as cheap raw materials. The mixed Recyclable Waste Activated Carbon was combined with trihexyl(tetradecyl)phosphonium Bis2,4,4-(trimethylpentyl)phosphinate (Cyphos® IL 104) ionic liquid to form an adsorbent with organic-inorganic content, in order to improve the Hg(II) uptake from aqueous solutions. FTIR confirms the presence of P, C=O and OH after this modification. The adsorption process was investigated and the evaluated results showed that the capacity was 124 mg/g at pH 4, with a contact time of 90 min, an adsorbent dose of 0.4 g/L, and a Hg(II) concentration of 50 mg/L. This Hg(II) adsorption capacity is superior than that reported in the literature for modified multiwall carbon nanotubes. The adsorption of Hg(II) on the modified activated carbon from mixed recyclable waste was found to follow the pseudo second-order kinetics model. Isotherms of adsorption were analyzed via Freundlich and Langmuir models. The results indicated that Freundlich is the best model to describe the process, suggesting multilayer adsorption.