Methoxy-Substituted Tyramine Derivatives Synthesis,Computational Studies and Tyrosinase Inhibitory Kinetics

Targeting tyrosinase for melanogenesis disorders is an established strategy. Hydroxyl-substituted benzoic and cinnamic acid scaffolds were incorporated into new chemotypes that displayed in vitro inhibitory effects against mushroom and human tyrosinase for the purpose of identifying anti-melanogenic ingredients. The most active compound 2-((4-methoxyphenethyl)amino)-2-oxoethyl (E)-3-(2,4-dihydroxyphenyl) acrylate (Ph9), inhibited mushroom tyrosinase with an IC₅₀ of 0.059 nM, while 2-((4-methoxyphenethyl)amino)-2-oxoethyl cinnamate (Ph6) had an IC₅₀ of 2.1 nM compared to the positive control, kojic acid IC₅₀ 16700 nM. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound (Ph9) and Ph6 exhibited 94.6% and 92.2% inhibitory activity respectively while the positive control kojic acid showed 72.9% inhibition. Enzyme kinetics reflected a mixed type of inhibition for inhibitor Ph9 (K_i 0.093 nM) and non-competitive inhibition for Ph6 (K_i 2.3 nM) revealed from Lineweaver–Burk plots. In silico docking studies with mushroom tyrosinase (PDB ID:2Y9X) predicted possible binding modes in the catalytic site for these active compounds. Ph9 displayed no PAINS (pan-assay interference compounds) alerts. Our results showed that compound Ph9 is a potential candidate for further development of tyrosinase inhibitors.     

Energy,exergy, and sensitivity analyses of a new integrated system for generation of liquid methanol,liquefied natural gas,and crude helium using organic Rankine cycle,and solar collectors

Journal of Thermal Analysis and Calorimetry - The increasing growth of helium consumption in industries and the limited resources of this element are the challenges that industries will face in the...     

A renewable approach to capture CO2 in Iran: thermodynamic and exergy analyses

Journal of Thermal Analysis and Calorimetry - This work presents numerical simulation of two-dimensional thermogravitational energy transport in a chamber filled with copper–water ( $${\hbox...     

Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis,molecular docking,and enzyme inhibitory kinetics

The porcine pancreatic elastase inhibition and free-radical scavenging play a crucial role in age progression. All the series of 10 newly synthesized benzimidazole thioureas ( 4a-j ) were assessed for elastase inhibition and radical scavenging activity to identify the suitable anti-aging ingredient for cosmetics products. The compounds 4e , 4f , 4g , and 4h showed inhibition better than the standard, while compound 4f showed the most significant elastase inhibition with the IC₅₀ value of 1.318 ± 0.025 μM compared with oleanic acid IC₅₀ 13.451 ± 0.014 used ±1.989 and 41.563 ± 0.824, respectively, as standard. Molecular docking studies were performed and the compound 4f showed binding energy of 7.2 kcal/mol. Kinetics studies revealed inhibition of the pancreatic elastase in a competitive manner. The relative binding energy and structure activity relationship (SAR) identified compound 4f as an effective inhibitor of porcine pancreatic elastase. Compounds 4e and 4i showed remarkable free-radical scavenging activity with SC₅₀ values of 26.421.     

Potassium phthalimide-catalysed one-pot multi-component reaction for efficient synthesis of amino-benzochromenes in aqueous media

2-Amino-4-aryl-4H-benzo[h]chromenes and 3-amino-1-aryl-1H-benzo[f]chromenes were prepared by treating cyano-methylene compounds (malononitrile or ethyl cyanoacetate), substituted aromatic aldehydes, and naphtholic compounds in the presence of potassium phthalimide as a green, mild, efficient, and commercially available organocatalyst in aqueous media. The procedure was readily conducted and affords remarkable advantages such as safety, short reaction times, environmentally benign milder reaction conditions, no organic solvent required, and high yields.     

Computational studies on the conformational preference of N-(Thiazol-2-yl) benzamide

N-(Thiazol-2-yl) benzamide 1 substructures are found in some of bioactive compounds. In some of protein/ligand co-crystals, the 1 moiety adopts a conformer in which the amide O and the thiazole S atoms are close. In fact, in the crystalline structure of 1 , the O—S distance is even shorter than Van der Waals radius. Although the natural bond orbital analysis finds a weak stabilizing interaction between O and S atoms, the attractive dipole–dipole interaction between the amide N─H and thiazole N atom seems to play a more significant role. Moreover, an intramolecular O—H hydrogen bonding in dimeric forms found to have an important role in the conformation preference of 1 . Computational details for the stability of conformers have been discussed using quantum theory of atoms in molecules, natural bond orbital (NBO) and noncovalent interaction index analysis.     

Exo/endo stereocontrolled synthesis of spiroindoloindolizidines by using classical and microwave conditions via the 1,3-dipolar cycloaddition reaction

Using both classical reflux and microwave-mediated conditions, a series of new spiroindoloindolizidines was synthesized by multicomponent 1,3-dipolar cycloaddition of azomethine ylides in unprecedented exo/endo stereocontrolled. Both conditions easily afforded two identical and separable exo/endo diastereomeric ratios of cycloadducts. However, the ratio of two diastereomeric products obtained from conventional conditions was reversed in all examined cases when the reactions were explored under microwave-mediated conditions. As expected, utilizing the microwave-assisted conditions produced higher yields and reaction rates compared to classical conditions. The structure and exact stereochemistry of synthesized cycloadducts were determined by applying various 2D-NMR spectroscopic techniques and single-crystal X-ray diffraction. Finally, the mechanism of the reaction has been briefly investigated by using density functional theory (DFT) calculations.     

Synthesis of heterocycles using nanomagnetic nickel catalysts

Abstract

Heterocyclic scaffolds are important components in the structure of many drugs and natural products. They are well-known compounds because of their broad spectrum of pharmaceutical and biological activities. In this paper, we provide an overview of the utilization of nickel complexes immobilized on magnetic nanoparticles as attractive and efficient catalytic systems for synthesis of heterocyclic molecules.     

Design,Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents

Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a–e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c–e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4′-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4′-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4′-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC₅₀ of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1.     

Numerical estimation of mixed convection heat transfer in vertical helically coiled tube heat exchangers

A numerical investigation of the mixed convection heat transfer from vertical helically coiled tubes in a cylindrical shell at various Reynolds and Rayleigh numbers, various coil‐to‐tube diameter ratios and non‐dimensional coil pitches was carried out. The particular difference in this study compared with other similar studies is the boundary conditions for the helical coil. Most studies focus on constant wall temperature or constant heat flux, whereas in this study it was a fluid‐to‐fluid heat exchanger. The purpose of this article is to assess the influence of the tube diameter, coil pitch and shell‐side mass flow rate on shell‐side heat transfer coefficient of the heat exchanger. Different characteristic lengths were used in the Nusselt number calculations to determine which length best fits the data and finally it has been shown that the normalized length of the shell‐side of the heat exchanger reasonably demonstrates the desired relation. Copyright © 2010 John Wiley & Sons, Ltd.