Coumarin-amino acid hybrids as promising anticancer agents: design, synthesis, docking studies and CK2 inhibition.

A series of mono-peptide, di-peptide and tri-peptide derivatives linked to a coumarin scaffold (5a-c, 7a-c, and 9a-c) were synthesized via the azide-coupling method from corresponding hydrazides 4, 6, and 8. These compounds were tested for anticancer activity against HepG-2, PC-3, and Hct-116 cell lines. Compounds, 7c, and 5b showed significant cytotoxicity, outperforming doxorubicin, with IC50 values of 34.07, 16.06, and 16.02 µM for 7c and 42.16, 59.74, and 35.05 µM for 5b. Compound 7b also displayed promising results with IC50 values of 72.13, 70.82, and 61.01 µM. Moreover, the key structural features of amino acids indicated that mono-peptide and di-peptide derivatives play a key role in increasing their anticancer activities compared with tri-peptides. In addition, the most potent compound 5b also exhibited strong CK2 kinase inhibition with an IC50 value of 0.117 ± 0.005 µM compared with roscovetine as a control drug with an IC50 value of 0.251 ± 0.011 µM. Finally, the binding mode of the chemical inhibitors at the active site of CK2 receptor was also investigated using a docking study which confirmed that the presence of the amino acid functionality is an important feature for anticancer activity and the synthesized compounds showed favorable ADME properties. Besides that, SAR analysis was implemented for the target compounds.

Highly selective BTX from catalytic fast pyrolysis of lignin over supported mesoporous silica.

The post synthesis of Al(3+) or Zr(4+) substituted MCM-48 framework with controlled acidity is challenging because the functional groups exhibiting acidity often jeopardize the framework integrity. Herein, we report the post-synthesis of two hierarchically porous MCM-48 composed of either aluminum (Al(3+)) or zirconium (Zr(4+)) clusters with high throughput. All prepared catalysts have been characterized by HR-TEM, XRD, IR, N2-adsorption, NH3-TPD, TGA and MAS NMR. They exhibit BET surface areas of 597 and 1112m(2)g(-1) for 8.4% Al/MCM-48 and 2.9% Zr/MCM-48, respectively. XRD analysis reveals that the hierarchical porosity of parental MCM-48 is reserved even after incorporation of Al(3+)or Zr(4+). Zr/MCM-48 catalysts are demonstrate a superior performance versus that of Al/MCM-48 and MCM-48 because of the mild (ZrO2) or nil (SiO2) Lewis acidity contributed from Zr-µ2-O group as well as smaller pore sizes suitable for the restriction of unwanted side reactions. The reaction conditions which were affecting the catalytic pyrolysis and final products were gas flow rate, pyrolysis temperature, and catalyst to lignin ratio. A total of 49% of BTX product were obtained over 2.9% Zr/MCM-48 at 600°C. The Lewis acid character was the governing factor which helps in pyrolysis and directly affects the BTX formation.

Synthesis of new thiolated acyclonucleosides with potential anti-HBV activity.

Treatment of the sodium salt of compounds 1, 7 or 12 with chloroethyl methyl ether, 2-chloroethyl toluoylate or 2-(2-chloro ethoxy)ethyl acetate afforded the corresponding derivatives 2, 3, 4, 8, 9, 13 and 14. Ammonolysis of 3, 4, 9 and 14 at room temperature gave the corresponding hydroxyalkyl derivatives 5, 6, 10, 11, and 15, respectively. Alkylation of 2,4-dithiouracil gave 2,4-dialkylthio pyrimidine.

Reactions with thiaxanthen-9-ol: new thiaxanthene derivatives with molluscicidal and nematocidal activity.

Thiaxanthen-9-ol (1) was condensed with nitriles 2a-e to yield the thiaxanthen-9-yl-acetonitriles 3a-e. With the thiols 7a-d, 1 yielded the thioethers 8a-d.