5,6-Diphenyl triazine-thio methyl triazole hybrid as a new Alzheimer's disease modifying agents.

In this study, new derivatives of 5,6-diphenyl triazine-thio methyl triazole hybrid were designed, synthesized and evaluated as multifunctional agents for Alzheimer's disease. Among all synthesized compounds, 4a and 4h showed the best inhibitory activities against BACE1 (40% and 37.5% µM inhibition at 50 µM, respectively). Molecular docking studies showed that compound 4a occupied the entire BACE1 enzyme and the thio triazine fragment deeply penetrates into S2 binding site via two hydrogen bonds with Thr72 and Gln73 amino acids. Different aromatic moieties occupy S'2 pocket via hydrophobic interactions. 6-Phenyl ring also had a potential hydrophobic interaction with S1 pocket. In vitro ChE inhibitory assay demonstrated that most of the derivatives exhibited more selectivity toward BuChE than AChE. 4c as the most potent BuChE inhibitor displayed an IC50 value of 6.4 µM, and 4b exhibited AChE inhibitory activity with 25.1% inhibition at 50 µM. Further, molecular docking studies revealed that the thiazolidinones moiety plays a key role in the inhibition mechanism by well fitting into the enzyme bounding pocket. Moreover, molecular docking study of 4a, 4b and 4c with ChE active site was also performed.

Organocatalytic Combinatorial Synthesis of Quinazoline, Quinoxaline and Bis(indolyl)methanes.

AIMS AND OBJECTIVE: An efficient and practical procedure for the synthesis of heterocyclic compounds such as quinazolines, quinoxalines and bis(indolyl)methanes was developed using 3,5-bis(trifluoromethyl) phenyl ammonium hexafluorophosphate (BFPHP) as a novel organocatalyst. MATERIALS AND METHODS: All of the obtained products are known compounds and identified by IR, 1HNMR, 13CNMR and melting points. RESULT: Various products were obtained in good to excellent yields under reaction conditions. CONCLUSION: The BFPHP organocatalyst demonstrates a novel class of non-asymmetric organocatalysts, which has gained much attention in green chemistry.

Solvent-mediated Highly Efficient Synthesis of [1,2,4]triazolo/benzimidazoloquinazolinone Derivatives.

OBJECTIVE: An efficient and catalyst-free procedure for the synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones has been developed in 2,2,2-trifluoroethanol or deep eutectic solvent(DESs) as a clean reaction media. METHODS: All of the obtained products are known compounds and identified by IR, 1HNMR,13CNMR, and melting points. RESULT: Various products were obtained in good to excellent yields under reaction conditions. CONCLUSION: We have efficiently developed a practical and catalyst-free approach for the synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones employing TFE as a clean and reusable media.

Multi-target inhibitors against Alzheimer disease derived from 3-hydrazinyl 1,2,4-triazine scaffold containing pendant phenoxy methyl-1,2,3-triazole: Design, synthesis and biological evaluation.

Alzheimer's disease (AD) is a complex neurological disorder with diverse underlying pathological processes. Several lines of evidence suggest that BACE1 is a key enzyme in the pathogenesis of AD and its inhibition is of particular importance in AD treatment. Ten new 3-hydrazinyl-1,2,4-triazines bearing pendant aryl phenoxy methyl-1,2,3-triazole were synthesized as multifunctional ligands against AD. We show that compounds containing Cl and NO2 groups at the para position of the phenyl ring, namely compounds 7c (IC50 = 8.55 ±â€¯3.37 µM) and 7d (IC50 = 11.42 ±â€¯2.01 µM), possess promising BACE1 inhibitory potential. Furthermore, we assessed the neuroprotective activities of 7c and 7d derivatives in PC12 neuronal cell line, which showed moderate protection against amyloid ß peptide toxicity. In addition, compound 7d demonstrated metal chelating activity and moderate antioxidant potential (IC50 = 44.42 ±â€¯7.33 µM). Molecular docking studies of these molecules revealed high-affinity binding to several amino acids of BACE1, which are essential for efficient inhibition. These results demonstrate that 1,2,4-triazine derivatives bearing an aryl phenoxy methyl-1,2,3-triazole have promising properties as therapeutic agents for AD.

Marine Sponge/H3PO4: As a Naturally Occurring Chiral Catalyst for Solvent-free Fischer-Indole Synthesis.

BACKGROUND: A new and efficient method have been developed for the synthesis of different indole derivatives from various ketones, having at least one hydrogen atom attached to each of their α-carbon atoms, and hydrazines in solvent-free conditions, using marine sponge/H3PO4 as a naturally occurring chiral catalyst. OBJECTIVES: This study recommended the use of marine sponge/H3PO4 as a naturally occurring chiral catalyst for preparation of phenylhydrazones from ketones having one α-hydrogen and subsequent cyclisation of the products to indoles. MATERIALS AND METHODS: The reaction was carried out by mixing the phenylhydrazine, ketone, and marine sponge/H3PO4 powder in mortar and pestle; the mixture was ground at room temperature in an appropriate time until TLC show the completion of the reaction. The product extracted by CH2Cl2 and evaporation of solvent yields the products. RESULTS: In this research work, several indoles are synthesized using phenylhydrazine and aliphatic or aromatic ketone as starting materials, in the presence of marine sponge/H3PO4 powder as a natural catalyst under solvent-free condition. CONCLUSIONS: We found marine sponge/H3PO4 to be an effective catalyst for indolisation of phenylhydrazones from ketones having α-hydrogens in solvent-free conditions.

A facile and one pot synthesis of 1,4-disubstituted-1H-1,2,3-triazoles from terminal alkynes and phenacyl azides prepared from styrenes by CAN oxidant and sodium azide.

A facile and green synthesis of 1,4-disubstituted-1H-1,2,3-triazoles is reported. The reaction of α-azido ketones and terminal alkynes in the presence of [CuSO(4) (H(2)O)(5)/sodium ascorbate] in a mixture of H(2)O/polyethylene glycol 400 as solvent afforded the corresponding 1,4-disubstituted triazoles at ambient temperature with short reaction times and at high yields. The corresponding α-azido ketones were directly prepared in situ from various substituted styrenes using the oxidant cerium ammonium nitrate and sodium azide in oxygen-saturated methanol.

Poly(ethylene glycol) grafted onto Dowex resin: an efficient, recyclable, and mild polymer-supported phase transfer catalyst for the regioselective azidolysis of epoxides in water.

In this study, an efficient method was designed to graft poly(ethylene glycol) effectively onto commercial Dowex resin. The catalytic efficiency of the copolymer obtained as a new solid-liquid phase transfer catalyst was studied. It was proved that this organocatalyst is an efficient heterogeneous catalyst for regioselective azidolysis of epoxide in water and gave azidohydrin in excellent yield under mild reaction conditions. The polymeric catalyst was easily recovered by simple filtration and showed no appreciable loss of activity when recycled several times.