Acids In Conjunction Research Articles

Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy.

Nutrient metabolism is regulated by several factors. Social determinants of health with or without genetics are the primary regulator of metabolism, and an unhealthy lifestyle affects all modulators and mediators, leading to the adaptation and finally to the exhaustion of cellular functions. Hepatic steatosis is defined by presence of fat in more than 5% of hepatocytes. In hepatocytes, fat is stored as triglycerides in lipid droplet. Hepatic steatosis results from a combination of multiple intracellular processes. In a healthy individual nutrient metabolism is regulated at several steps. It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component. Several hormones, peptides, and genes have been described that participate in nutrient metabolism. Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP. As of now several publications have revealed very intricate regulation of nutrient metabolism, where most of the regulatory factors are tied to each other bidirectionally, making it difficult to comprehend chronological sequence of events. Insulin hormone is the primary regulator of all nutrients' metabolism both in prandial and fasting states. Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes; metabolic, inflammation and repair, and cell growth and regeneration. Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands, adiponectin, leptin, and adiponutrin. Insulin hormone has direct effect on these final modulators. Whereas blood glucose level, serum lipids, incretin hormones, bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle. The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) that help us understand the disease natural course, risk stratification, role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine. PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states; MASLD, cardiovascular disease and cancer. More than 1000 publications including original research and review papers were reviewed.

GBM tumors are heterogeneous in their fatty acid metabolism and modulating fatty acid metabolism sensitizes cancer cells derived from recurring GBM tumors to temozolomide.

Glioblastoma is a highly lethal grade of astrocytoma with very low median survival. Despite extensive efforts, there is still a lack of alternatives that might improve these prospects. We uncovered that the chemotherapeutic agent temozolomide impinges on fatty acid synthesis and desaturation in newly diagnosed glioblastoma. This response is, however, blunted in recurring glioblastoma from the same patient. Further, we describe that disrupting cellular fatty acid homeostasis in favor of accumulation of saturated fatty acids such as palmitate synergizes with temozolomide treatment. Pharmacological inhibition of SCD and/or FADS2 allows palmitate accumulation and thus greatly augments temozolomide efficacy. This effect was independent of common GBM prognostic factors and was effective against cancer cells from recurring glioblastoma. In summary, we provide evidence that intracellular accumulation of saturated fatty acids in conjunction with temozolomide based chemotherapy induces death in glioblastoma cells derived from patients.

Organic acids in conjunction with various oilseed sunflower cultivars promote Cd phytoextraction through regulating micro-environment in root zone

Exogenous chelates in conjunction with phytoextraction have been demonstrated as a prominent potential for remediating Cd-contaminated soils. Among bath chelates, low molecular-weight organic acids have the advantages of smaller impact on plant growth and lower negative effects on soil environment. In this research, oilseed sunflowers were selected as the main extraction plants, and the Cd phytoextraction effects of different cultivars, varies organic acid types and concentrations combinations were systematically examined. Results showed that adding exogenous organic acids improved biomass of all issues, but the increase varied with the cultivar. For both cultivars, their biomass increase with acid application concavely, with the acid application rate at which the biomass peaked differed between the two cultivars. Adding exogenous acids boosted Cd concentration in roots and shoots in general, but it reduced the Cd content in seeds as well as the rhizosphere and bulk soil. In addition to its impact on Cd, application of organic acids also reduced nutrient and salinity in the rhizosphere and promoted root uptake of nutrients as a result. Cd content plant an soil was closely related to nutrients in soil and plant. The organic acids reduced soil Cd and nutrients in soil proximal to the roots. It was also found that adding acids reduced Cd content in the top 0–10 cm soil but increased the Cd content in the 10–30 cm soil, alluding a potential leaching. Therefore, adding organic acids to improve phytoremediation of Cd needs to proceed with care.

Vesicle Self-Assembly of Monoalkyl Amphiphiles under the Effects of High Ionic Strength, Extreme pH, and High Temperature Environments.

Vesicles and other bilayered membranous structures can self-assemble from single hydrocarbon chain amphiphiles. Their formation and stability are highly dependent on experimental conditions such as ionic strength, pH, and temperature. The addition of divalent cations, for example, often results in the disruption of vesicles made of a single fatty acid species through amphiphile precipitation. However, membranes composed of amphiphile mixtures have been shown to be more resistant to low millimolar concentrations of divalent cations at room temperature. In this report, several mixtures of amphiphiles are examined for their propensity to self-assemble into membranous vesicular structures under extreme environmental conditions of low pH, high ionic strengths, and temperatures. In particular, mixtures of decylamine with polar cosurfactants were found to efficiently form membranes under these conditions far away from those normally supporting vesicle formation. We further examined decanoic acid/decylamine mixtures in detail. At pH 2 in low ionic strength solutions, the amphiphiles formed oily or crystalline structures; however, the introduction of salts or/and strong acids in conjunction with high temperature induced a stable vesiculation. Thus, extreme environments, such as volcanic or vent environments whose environmental conditions are known to support high chemical reactivity, could have harbored and most significantly promoted the formation of simple organic compartments that preceded cells.

Assessment of Adulteration of Cosmetics Based on Vegetable Oils by GC-FID and Lipid Profile Using Direct Infusion Electrospray Ionization Mass Spectrometry (ESI-MS)

Vegetable oils have properties that are beneficial to the human skin, and so, they are being used increasingly as ingredients of many cosmetic preparations; however, they are targets of adulteration. This study will evaluate the authenticity of Brazilian cosmetics based on vegetable oils (sesame, peanut, sunflower, and almonds) to determine the composition of fatty acids by gas chromatography with flame ionization detection (GC-FID) and the percentage of fatty acids in conjunction with chemometric treatments (principal component analysis), and lipid profiles using direct infusion electrospray ionization mass spectrometry (ESI-MS). The results obtained were compared with the respective pure vegetable oils. Of the seven brands analyzed, three were revealed as authentic, three were found to be adulterated with the addition of large amounts of soybean oil, and one showed no vegetable oils. These results demonstrate the relevance of quality control for cosmetics based on vegetable oils, which are more susceptible to adulteration owing to their higher cost when compared with vegetable oils such as soybean.

Synthesis and Characterization of Some Ester-type Biolubricants of Soiabean Fatty Acids

Growing demands from industry for the use of eco-friendly lubricants led research towards finding environmentally friendly products with superior lubricating characteristics. Vegetable oils and synthetic ester oils are competitive base oils used to obtain lubricants with good physico-chemical, rheological and tribotechnical properties, biodegradable lubricants without negative environmental impacts. In this study we aimed the synthesis and characterization of bioesters with lubricant properties, using as acid component the soybean oil fatty acids in conjunction with the following hydroxyl compounds n-buthanol (P1) and 1,2-propilenglycole (P2), respectively. These complex esters were synthesized in a microwave reactor in a single stage in the presence of the catalyst at the reflux temperature. Characterization was carried out in the respective of structural point of view and as a lubricant.

Effect of Medium Chain Triglycerides on TCA and Ketogenic Capacity of Proximal Intestinal Fatty Acid Oxidation in Clofibrate Feed Newborn Pigs

Newborn pigs are much less efficient at utilizing milk fat as an energy source, than weaned pigs, due to a limited capacity of fatty acid oxidation. We have previously shown that clofibrate, a PPARα agonist, increases fatty acid oxidation levels in newborn pigs by increasing production of key metabolic enzymes. We hypothesize that feeding anaplerotic carbon sources or ketogenic fatty acids in conjunction with clofibrate will improve energy utilization in young pigs by increasing capacities of the TCA cycle or ketogenic activity. To test our hypothesis, suckling newborn pigs (N=48) from 6 litters, which received colostrum for 24 hours, from the North Carolina State University Swine Unit were randomly divided into a 2 (control vs clofibrate) × 4 (glycerol‐succinate, valerate, hexonoate, 2‐methylpentanoate) factorial design. All piglets were fed a standard milk replacer three times a day based on body weight (1.31±.2kg). All supplements, glycerol‐succinate (GS), triglycerides of valeric acid (triC5), hexanoic acid (triC6) or tri‐2‐methylpentanoate (2‐MPA), were fed at ~5% (w/w as fed to maintain an isocaloric diet). For the clofibrate treatment groups, clofibrate was included (.35%) only in the morning feedings. Milk was withheld on the sixth day when the mucosa was collected from the proximal small intestine. The mucosa (28.43±6.12 mg/mL protein) was homogenized and added to flasks that contained a buffer without (control) or with carnitine (1mM), L659699 (1.6 μM), or iodoacetamide (50 μM) and labeled [1–14C] palmitic acid (1mM) as the substrate. L659599 is an inhibitor of both mitochondria and cytosolic hydroxymethylglutaryl‐CoA synthase and iodoacetamide is an inhibitor of acetoacetate synthesis. After 30 mins, the reactions were terminated and 14C accumulation in CO2 and acid soluble products (ASP) was measured to determine fatty acid oxidation rates. The oxidation of palmitic acid (14C accumulations in CO2 +ASP; μmol/h.mg protein) was higher (P < 0.0001) in the pigs that received triC5 (1.54) and triC6 (1.51) than those that received GS (1.27) or 2‐MPA (1.47). No differences were detected between pigs receiving triC5 and triC6 or between GS and 2‐MPA. Clofibrate had no effects on the palmitic acid oxidation from pigs fed GS or triC6, but the 14C accumulation in CO2 and ASP was increased by 40% and 26% in pigs receiving triC5 and 2‐MPA (P <0.0003), respectively. Addition of carnitine with or without clofibrate increased palmitic acid oxidation by 44% as compared with the control (P < 0.0001), while oxidation was reduced by 9% by L659699 (P < 0.004). Oxidation rates in incubations with iodoacetamide were higher than with L659699 (P < 0.03), but were not different from controls (P =0.92). The results indicate that fatty acid oxidation in the mucosa of the proximal small intestine of newborn pigs could be increased by enhancing ketogenic activity and TCA cycle capacity, thus demonstrating that dietary supplementation of ketogenic fatty acid and anaplerotic carbon would be favorable to improve milk fat utilization in pigs during the postnatal period.Support or Funding InformationSupported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, under award number 2015‐67015‐23245.

Replication trial of omega‐3s shows no effect in preventing psychosis

A randomized clinical trial involving more than 300 patients has found no benefit from omega‐3 polyunsaturated fatty acids in conjunction with cognitive therapy in preventing onset of psychotic illness in at‐risk young adults. The trial, results of which were published online Nov. 23, 2016, in JAMA Psychiatry, failed to replicate results of an earlier study indicating that omega‐3s were superior to placebo in reducing the risk of transition to psychosis.

Solvation behaviour of some amino acids in aqueous solutions of an antibiotic drug streptomycin sulfate at different temperatures: Volumetric, acoustic and viscometric approach

The volumetric, acoustic and viscometric approach has been used for investigating the interactions of l-serine, l-threonine and l-leucine in aqueous solutions of an antimycobacterial drug, namely, streptomycin sulfate, over a temperature range of (305.15, 310.15 and 315.15) K at atmospheric pressure. The apparent molar volume, Vϕ, limiting apparent molar volume, V0ϕ, the slope, Sv, partial molar volume of transfer, V0ϕ, tr, limiting apparent molar expansivity, E0ϕ, and Hepler's constant, (∂2V0ϕ/∂T2)P, have been calculated from density data. The apparent molar isentropic compression, Kϕ,s, limiting apparent molar isentropic compression, K0ϕ,s, its slope, Sk, and partial molar isentropic compression of transfer, K0ϕ,s,tr, have been calculated from speed of sound data. The compression data is also used for calculating the number of water molecules hydrated, nH, to the amino acids. The viscosity data has been used to determine relative viscosity ηr, viscosity B-coefficients, temperature derivative of B-coefficients, dB/dT and viscosity B-coefficients of transfer, Btr. Solvation behaviour, of amino acids has also been computed. The calculated parameters have been discussed in terms of various solute–solute and solute–solvent interactions prevailing in these solutions. Further, a detailed insight into the physicochemical interactions, e.g., ion-hydrophilic and hydrophilic–hydrophilic interactions in the amino acids in conjunction with the drug along with the structure-making/structure-breaking tendency has been retrieved through the perusal of these calculated parameters.

Mechanistic insights on cooperative asymmetric multicatalysis using chiral counterions.

Cooperative multicatalytic methods are steadily gaining popularity in asymmetric catalysis. The use of chiral Brønsted acids such as phosphoric acids in conjunction with a range of transition metals has been proven to be effective in asymmetric synthesis. However, the lack of molecular-level understanding and the accompanying ambiguity on the role of the chiral species in stereoinduction continues to remain an unresolved puzzle. Herein, we intend to disclose some novel transition state models obtained through DFT(B3LYP and M06) computations for a quintessential reaction in this family, namely, palladium-catalyzed asymmetric Tsuji-Trost allylation of aldehydes. The aldehyde is activated as an enamine by the action of a secondary amine (organocatalysis), which then adds to an activated Pd-allylic species (transition metal catalysis) generated through the protonation of allyic alcohol by chiral BINOL-phosphoric acid (Brønsted acid catalysis). We aim to decipher the nature of chiral BINOL-phosphates and their role in creating a quaternary chiral carbon atom in this triple catalytic system. The study reports the first transition state model capable of rationalizing chiral counterion-induced enantioselectivity. It is found that the chiral phosphate acts as a counterion in the stereocontrolling event rather than the conventional ligand mode.

Role of ferrocyanides in the prebiotic synthesis of α-amino acids.

We investigated the synthesis of α-amino acids under possible prebiotic terrestrial conditions in the presence of dissolved iron (II) in a simulated prebiotic ocean. An aerosol-liquid cycle with a prebiotic atmosphere is shown to produce amino acids via Strecker synthesis with relatively high yields. However, in the presence of iron, the HCN was captured in the form of a ferrocyanide, partially inhibiting the formation of amino acids. We showed how HCN captured as Prussian Blue (or another complex compound) may, in turn, have served as the HCN source when exposed to UV radiation, allowing for the sustained production of amino acids in conjunction with the production of oxyhydroxides that precipitate as by-products. We conclude that ferrocyanides and related compounds may have played a significant role as intermediate products in the prebiotic formation of amino acids and oxyhydroxides, such as those that are found in iron-containing soils and that the aerosol cycle of the primitive ocean may have enhanced the yield of the amino acid production.

Dysglycemia and Abdominal Obesity

Dysglycemia as a pre-stage of diabetes mellitus and abdominal obesity are closely interrelated at multiple levels and by a whole array of complex mechanisms, many of which seem to have the potential of causing harm to large blood vessels, in particular to coronary and peripheral vascular segments. Both conditions are associated with elevated circulating concentrations of free fatty acids in conjunction with insulin resistance, oxidative stress, mitochondrial dysfunction, disordered nitric oxide release, and endothelial dysfunction. Oscillating glucose levels seem to be associated with the most of the injury burden to endothelial cells of large blood vessels and also generate some kind of metabolic memory. In addition, the multiple effects of insulin also on the regulation of the vasculature are shifted towards vasoconstriction and proliferation in the context of insulin resistance and the excessively high levels.

The effect of Omega-3 fatty acids on the atherogenic lipoprotein phenotype in patients with nephrotic range proteinuria

Patients with nephrotic range proteinuria are known to have an increased risk of cardiovascular disease partly due to possessing the atherogenic lipoprotein phenotype. The aim of this study was to examine the effect of high dose omega-3 fatty acids on atherogenic triglyceride rich lipoproteins in patients with nephrotic range proteinuria, comparing their effect on lipoprotein profiles in age and sex matched controls. 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied. Fasting lipids and lipoproteins were measured before and after 8 weeks treatment with 4 g daily of omega-3 fatty acids (Omacor®). In patients with proteinuria treatment reduced plasma triglyceride by a mean of 0.45 mmol/l (95%CI 0.16 - 0.74, p = 0.005) and plasma very low density lipoprotein cholesterol by a mean of 0.38 (95%CI 0.01 - 0.75, p = 0.04). LDL III concentration fell from 178.8 mg/dl (61.6 - 231.0) to 96.1 mg/dl (49.3 - 204.5), p = 0.05. In patients treatment altered the LDL profile so that LDLIII which was the major subfraction present at baseline was reduced from 49.9% to 29.8% (p = 0.01). Remnant lipoproteins (RLP) also fell with a mean reduction of 3.5 mg/dl in RLP-Cholesterol (95%CI 0.1 - 6.9, p = 0.05) and 12.4 mg/dl in RLP-triglyceride (95%CI 2.6 - 22.2, p = 0.03). There was however a 0.6 mmol/l rise in LDL-C (p = 0.06) in the patients. Treatment did not alter HDL-C. In patients with nephrotic range proteinuria, omega-3 fatty acids reduced triglyceride rich lipoproteins, LDL III and remnant lipoproteins. A tendency to an increase in LDL-C was observed but this was offset by an alteration in the distribution of the LDL profile towards lighter, larger LDL particles. We propose that treatment with omega-3 fatty acids in conjunction with a statin may be the ideal therapy in these patients.

The effects of added sulphur amino acids, threonine and an ideal amino acid ratio on nitrogen metabolism in mature, overweight dogs

The objectives of this study were to investigate the effects of added essential amino acids in conjunction with a dietary lysine/MJ of 0.72 on nitrogen (N) metabolism in dogs. Treatments were; a control diet, a diet that provided an ideal amino acid profile (IAA), a diet with added total sulphur amino acids (TSAA), and a diet with added TSAA and threonine (TT). Diets were fed to eight overweight, mature, female hounds using a replicated 4 × 4 Latin Square design. Food intake was similar across treatments, however, food N intake was higher (p < 0.001) for TSAA than control, IAA or TT. Nitrogen absorbed was higher (p < 0.01) for TSAA than IAA and control. Urea N excretion was greater for control than TT (p < 0.05). Urine N excretion did not differ between diets. There were no differences in digestibility or N retention of diets. There were no differences in protein turnover, synthesis, or degradation. Blood metabolites were within normal ranges and did not differ due to dietary treatment. Based on the measurements made in this study, there is no benefit for added TSAA, TT or additional EAA in diets for mature dogs formulated to provide a 0.72 g lysine/MJ ME ratio.

Effects of omega-3 supplementation in combination with diet and exercise on weight loss and body composition

In addition to the metabolic and cardiovascular benefits of omega-3 (n-3) fatty acids, several studies have suggested an added weight loss-enhancing benefit to this supplement. The objective was to assess whether supplemental omega-3 fatty acids in conjunction with diet and exercise augment weight loss over a 6-mo period. In a single-institution, placebo-controlled, randomized clinical trial, 128 individuals with a body mass index (in kg/m(2)) between 26 and 40 were assigned to receive 5 omega-3 [3.0 g eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) at a 5:1 ratio (EPA:DHA)] or placebo capsules daily in conjunction with lifestyle modification. The primary endpoint was weight loss; secondary endpoints included metabolic and psychometric variables. Analyses were by intention-to-treat. Overweight and obese individuals were assigned to the omega-3 arm (n = 64) or to the placebo arm (n = 64). Subjects in both arms received dietary and exercise counseling. Eighty-one individuals completed the 24-wk study, and the dropout rate was 27%. Subjects in both arms lost an average of >5% of their body weight. No significant differences in weight loss were observed between the omega-3 (-5.2 kg; 95% CI: -6.0, -4.4 kg) and placebo (-5.8 kg; 95% CI: -6.7, -5.1 kg) arms. The absolute mean (±SEM) change difference was 0.61 ± 0.58 kg (P = 0.29). In addition, no significant differences in the other factors assessed were observed. Omega-3 fatty acids were not effective as an adjunct for weight loss in this otherwise healthy, overweight population.

A high fat diet reduces the expression of lipogenic, lipolytic and oxidative genes in white adipose tissue. The effect of the concentration and type of fatty acid is dependent of the dietary protein

It has been postulated that not only the quantity, but also the type of dietary fat has important implications in the metabolism of lipids and glucose, therefore in obesity. Fatty acids are important mediators of gene expression of metabolic enzymes in the liver, whereas its role in adipose tissue, also involved in metabolism homeostasis, has been little studied. The present study shows that in white adipose tissue of hyperleptinemic and hyperinsulinemic Zucker fa/fa rats chronically fed 5% polyunsaturated fatty acids (PUFA), the expression of genes involved in lipogenesis (SREBP‐1, ACC, FAS, SCD‐1), fatty acid oxidation (PPARα, CPT‐1, UCP‐1, 2 and 3 and AOX) and glucose homeostasis (AMPKα, LKB1 and GLUT4) was dependent by the type of protein consumed (casein or soy), maintaining in both the functionality of the adipocyte. However, if the amount of fat increased in the diet (10%), the expression of all the measured genes was abated drastically, including the lipolytic ones (HSL and perilipin). Gene expression was dependent of the type of fat consumed (PUFA or saturated fatty acids) as well as of the type of protein. Of the four groups tested with 10% of dietary fat, the least affected was the group fed PUFA with soy protein. The action of the different sort of fatty acids in conjunction with the type of protein as regulators of gene expression in the adipose tissue was independent of insulin and leptin.Supported by the INCMNSZ

Profiling Pancreatic Cancer-Secreted Proteome Using 15N Amino Acids and Serum-Free Media

A new method of determining protein turnover by labeling protein with N amino acids was used in conjunction with serum-free cell culture to profile secreted proteins that are released by MIA PaCa-2 pancreatic cancer cells in culture. MIA PaCa-2 cells were first cultured in Dulbecco modified Eagle medium (Gibco by Invitrogen, Carlsbad, Calif) with 10% fetal bovine serum, then in serum-free modified Eagle medium with or without 50% N algal amino acid mixture. The effect of oxythiamine chloride on secreteome was studied. Secreteome from cell culture media was analyzed by 2-dimensional (2D) gel electrophoresis. Differentially expressed proteins were detected and identified. Protein turnover rates were calculated according to the newly established method. Western blot and enzyme-linked immunosorbent assay were used to validate identified proteins. Among the 14 differentially expressed proteins after oxythiamine treatment, tissue inhibitor of metalloproteases-1 and cytokeratin-10 were identified as 2 newly synthesized secreted proteins caused by substantial N incorporation. The inhibition of tissue inhibitor of metalloproteases-1 expression in MIA PaCa-2 cells by oxythiamine treatment was first demonstrated by 2D gel electrophoresis and further validated by Western blotting and enzyme-linked immunosorbent assay analyses. Our method of labeling protein with N amino acids in conjunction with serum-free cell culture allows the identification of actively secreted proteins from pancreatic cancer cells and is a useful method for serum biomarker discovery.

A universal approach for continuum solvent pK a calculations: are we there yet?

This paper reviews several pKa calculation strategies that are commonly used in aqueous acidity predictions. Among those investigated were the direct or absolute method, the proton exchange scheme, and the hybrid cluster–continuum (Pliego and Riveros) and implicit–explicit (Kelly, Cramer and Truhlar) models. Additionally, these protocols are applied in the pKa calculation of 55 neutral organic and inorganic acids in conjunction with various solvent models, including the CPCM-UAKS/UAHF, IPCM, SM6 and COSMO-RS, with a view to identifying a universal approach for accurate pKa predictions. The results indicate that the direct method is unsuitable for general pKa calculations, although moderately accurate results (MAD <3 units) are possible for certain classes of acids, depending on the choice of solvent model. The proton exchange scheme generally delivers good results (MAD <2 units), with CPCM-UAKS giving the best performance. Furthermore, the sensitivity of this approach to the choice of reference acid can be substantially lessened if the solvation energies for ionic species are calculated via the IPCM cluster–continuum approach. Reference-independent hybrid approaches that include explicit water molecules can potentially give reasonably accurate values (MAD generally ~2 units) depending on the solvent model and the number of explicit water molecules added.

Synthesis of Second-Generation Sansalvamide A Derivatives: Novel Templates as Potential Antitumor Agents

We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.

Coupling Reaction of CO2 with Epoxides by Binary Catalytic System of Lewis Acids and Onium Salts

Various off-the-shelf Lewis acids in conjunction with various onium salts are screened for coupling reaction of <TEX>$CO_2$</TEX> with epoxides. Among the tested ones, <TEX>$VCl_3/n-Bu_4NOAc$</TEX>, <TEX>$VCl_3/(n-Bu_4NCl$</TEX> or PPNCl), <TEX>$FeCl_3/ n-Bu_4NOAc$</TEX>, and <TEX>$FeCl_3/ n-Bu_4NOAc$</TEX>are proved to be highly active. Propylene oxide, epichlorohydrin, styrene oxide, and cyclohexene oxide can be converted over 90% yields to the corresponding cyclic carbonates without the use of organic solvents under mild conditions by 0.1-1.0 mol% catalyst charge.