Microwave-Mediated, Catalyst-Free Synthesis of 1,2,4-Triazolo[1,5-a]pyridines from Enaminonitriles.

A catalyst-free, additive-free, and eco-friendly method for synthesizing 1,2,4-triazolo[1,5-a]pyridines under microwave conditions has been established. This tandem reaction involves the use of enaminonitriles and benzohydrazides, a transamidation mechanism followed by nucleophilic addition with nitrile, and subsequent condensation to yield the target compound in a short reaction time. The methodology demonstrates a broad substrate scope and good functional group tolerance, resulting in the formation of products in good-to-excellent yields. Furthermore, the scale-up reaction and late-stage functionalization of triazolo pyridine further demonstrate its synthetic utility. A plausible reaction pathway, based on our findings, has been proposed.

Total Synthesis of Isohericerinol A and Its Analogues to Access Their Potential Neurotrophic Effects.

The secondary metabolites from Hericium erinaceus are well-known to have neurotrophic and neuroprotective effects. Isohericerinol A (1), isolated by our colleagues from its fruiting parts has a strong ability to increase the nerve growth factor secretion in C6 glioma cells. The current work describes the total synthesis of 1 and its regioisomer 5 in a few steps. We present two different approaches to 1 and a regiodivergent approach for both 1 and 5 by utilizing easily accessible feedstocks. Interestingly, the natural product 1, regioisomer 5, and their intermediates exhibited potent neurotrophic activity in in vitro experimental systems. Thus, these synthetic strategies provide access to a systematic structure-activity relationship study of natural product 1.

Design, Synthesis, and Cytotoxicity and Topoisomerase I/IIα Inhibition Activity of Pyrazolo[4,3-f]quinoline Derivatives.

With the several targets of cancer treatment, inhibition of DNA topoisomerase activity is one of the well-known focuses in cancer chemotherapy. Here, we describe the design and synthesis of a novel series of pyrazolo[4,3-f]quinolines with potential anticancer/topoisomerase inhibition activity. Forty newly designed pyrazolo[4,3-f]quinoline derivatives were synthesized via inverse imino Diels-Alder reaction. The antiproliferative activity of the synthesized derivatives was initially measured in the human NUGC-3 cancer cell line. Then, the selected compounds 1B, 1C, 1M, 2A, 2D, 2E, 2F, and 2R with higher activity among tested compounds were screened against six cancer cell lines, including ACHN, HCT-15, MM231, NCI-H23, NUGC-3, and PC-3. The results demonstrated that the compounds 1M, 2E, and 2P were most effective in all cancer cell lines exhibiting GI50 below 8 µM. Among them, 2E showed an equivalent inhibition pattern of topoisomerase IIα activity to that of etoposide, positive control at a 100 µM dose.

Inhibitory Effect of Chlorogenic Acid Analogues Comprising Pyridine and Pyrimidine on α-MSH-Stimulated Melanogenesis and Stability of Acyl Analogues in Methanol.

In continuation of studies for α-MSH stimulated melanogenesis inhibitors, we have evaluated the design, synthesis, and activity of a new series of chlorogenic acid (CGA) analogues comprising pyridine, pyrimidine, and diacyl derivatives. Among nineteen synthesized compounds, most of them (fifteen) exhibited better inhibitions of melanin formation in B16 melanoma cells. The results illustrated that a pyridine analogue 6f and a diacyl derivative 13a of CGA showed superior inhibition profiles (IC50: 2.5 ± 0.7 µM and 1.1 ± 0.1 µM, respectively) of α-MSH activities than positive controls, kojic acid and arbutin (IC50: 54 ± 1.5 µM and 380 ± 9.5 µM, respectively). The SAR studies showed that both -CF3 and -Cl groups exhibited better inhibition at the meta position on benzylamine than their ortho and para positions. In addition, the stability of diacyl analogues of CGA in methanol monitored by HPLC for 28 days indicated the steric bulkiness of acyl substituents as a key factor in their stability.

Characterization of Interfacial Microstructure of Cast Iron Inserts Dipping in Aluminum Alloy Melt.

Commercial vehicle pistons should have low thermal expansion and should be able to withstand deformation or mechanical stress. Aluminum alloys are suitable for pistons due to their light weight. However, as aluminum alloys have low strength and friction resistance, cast iron is added through the dipping process in order to increase the quality of pistons. However, the dipping process leads to defects such as defective bonding, void formation, and formation of an oxidation film at the junctions of the two materials due to differences in their properties, which adversely affects the impact resistance and mechanical strength of the product. A theoretical study on the metallurgical bond between the aluminum alloy and the cast iron insert in the piston was conducted to investigate the cause of the defects. The microstructure of the intermetallic bonding layer was observed using scanning electron microscopy and electron dispersive spectroscopy. In this study, defects were found in non-bonding and oxide films and several phases were generated corresponding to different parameters. It was found that processing time and temperature were the main causes of these defects.

α-Hydroxy acid as an aldehyde surrogate: metal-free synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and other N-heterocycles via decarboxylative oxidative annulation reaction.

A metal-free and efficient procedure for the synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and indolo[1,2-a]quinoxaline has been developed. The key features of our method include the in situ generation of aldehyde from α-hydroxy acid in the presence of TBHP (tert-butyl hydrogen peroxide), and further condensation with various amines, followed by intramolecular cyclization and subsequent oxidation to afford the corresponding quinoxalines, quinazolinones derivatives in moderate to high yields.

The associations among vitamin D deficiency, C-reactive protein, and depressive symptoms.

OBJECTIVE: Vitamin D deficiency has been reported to be associated with depression, but the underlying mechanisms aren't well understood. Our study aims to investigate the associations among serum vitamin D, C-reactive protein (CRP) level, and depressive symptoms. METHODS: Serum levels of Vitamin D and CRP were measured from 52,228 participants. Depressive symptoms were assessed using a Korean version of the CES-D scale. We used logistic regression to calculate the odds ratio (ORs) of depressive symptoms according to vitamin D and CRP levels. The regressions were adjusted for covariates, and each model was adjusted mutually for vitamin D and CRP levels. RESULTS: A significant difference was found in vitamin D status between depressed and non-depressed participants, but CRP status was not significantly different. The OR for the presence of depressive symptoms was significantly increased in participants with vitamin D deficiency after adjusting for potentially confounding factors (Adjusted OR=1.158, 95% CI=1.003-1.336, p=0.046). The OR of depressive symptoms was not significantly increased in individuals with high (3.01-10mg/L) CRP level compared to individuals with low (≤3mg/L) CRP level (Adjusted OR=1.004, 95% CI=0.821-1.227, p=0.97). There was no significant association between vitamin D and CRP level. Additional adjustment for serum CRP level did not weaken the resulting association between vitamin D deficiency and the presence of depressive symptoms. CONCLUSION: Vitamin D deficiency was associated with depressive symptoms, but elevated serum CRP level was not. The results indicate that CRP level does not account for the association between vitamin D deficiency and the presence of depressive symptoms.