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Molecules (Basel, Switzerland) Jul 2022To realize the commercialization of sustainable materials, new polymers must be generated and systematically evaluated for material characteristics and end-of-life...
To realize the commercialization of sustainable materials, new polymers must be generated and systematically evaluated for material characteristics and end-of-life treatment. Polyester polyols made from renewable monomers have found limited adoption in thermoplastic polyurethane (TPU) applications, and their broad adoption in manufacturing may be possible with a more detailed understanding of their structure and properties. To this end, we prepared a series of bio-based crystalline and amorphous polyester polyols utilizing azelaic acid and varying branched or non-branched diols. The prepared polyols showed viscosities in the range of 504-781 cP at 70 °C, with resulting TPUs that displayed excellent thermal and mechanical properties. TPUs prepared from crystalline azelate polyester polyol exhibited excellent mechanical properties compared to TPUs prepared from amorphous polyols. These were used to demonstrate prototype products, such as watch bands and cup-shaped forms. Importantly, the prepared TPUs had up to 85% bio-carbon content. Studies such as these will be important for the development of renewable materials that display mechanical properties suitable for commercially viable, sustainable products.
Topics: Alcohols; Dicarboxylic Acids; Polyesters; Polyurethanes
PubMed: 35956835
DOI: 10.3390/molecules27154885 -
Biomolecules Oct 2019In addition to our previous efforts toward bioenzymatic and chemical transformations of ricinoleic acid and oleic acid to their corresponding ,-dicarboxylic acids via...
In addition to our previous efforts toward bioenzymatic and chemical transformations of ricinoleic acid and oleic acid to their corresponding ,-dicarboxylic acids via their ester intermediates driven in cells, several efficient oxidation conditions were investigated and optimized for the conversion of -hydroxycarboxylic acids to ,-dicarboxylic acids. Pd/C-catalyzed oxidation using NaBH in a basic aqueous alcohol and Ni(II) salt-catalyzed oxidation using aqueous sodium hypochlorite were considered to be excellent as a hybrid reaction for three successive chemical reactions (hydrogenation, hydrolysis, and oxidation) and an eco-friendly, cost-effective, and practical approach, respectively. Omega-hydroxycarboxylic acids and -aminocarboxylic acid were also easily prepared as useful building blocks for plastics or bioactive compounds from the bioenzymatically driven ester intermediate. The scope of the developed synthetic methods can be utilized for large-scale synthesis and various derivatizations.
Topics: Borohydrides; Dicarboxylic Acids; Green Chemistry Technology; Hydrogenation; Hydrolysis; Oxidation-Reduction; Ricinoleic Acids
PubMed: 31590242
DOI: 10.3390/biom9100566 -
Clinica E Investigacion En... May 2021We review all the phase II and III studies carried out with bempedoic acid at the dose of 180mg, alone or in combination with different lipid-lowering drugs and in... (Review)
Review
We review all the phase II and III studies carried out with bempedoic acid at the dose of 180mg, alone or in combination with different lipid-lowering drugs and in different subgroups of patients that unequivocally show the efficacy and safety of the drug. We point out some of the potential advantages of its use in clinical practice in patients with statin intolerance and the efficacy in reducing LDL-c when combined with statins, and with statins and ezetimibe, as well as in reducing inflammation markers pending the results of the CV Clear Outcomes trial that will end in 2022.
Topics: Cholesterol, LDL; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dicarboxylic Acids; Drug Development; Drug Therapy, Combination; Ezetimibe; Fatty Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Inflammation
PubMed: 33966815
DOI: 10.1016/j.arteri.2021.02.005 -
Journal of the American Chemical Society Aug 2020The intriguing structure of tagetitoxin (), a long-standing challenge in natural product synthesis, has been the subject of multiple revisions and has been confirmed...
The intriguing structure of tagetitoxin (), a long-standing challenge in natural product synthesis, has been the subject of multiple revisions and has been confirmed through total synthesis. The route commences from a renewable furan starting material and features a number of unusual transformations (such as rearrangements, bromocyclization, and P(V)-based phosphate installation) to arrive at the target in 15 steps. As the route was designed to enable access to both enantiomers, the absolute configuration of the natural product could be assigned using a bioassay on (+)- and (-)-.
Topics: Dicarboxylic Acids; Molecular Structure; Organophosphorus Compounds; Stereoisomerism
PubMed: 32687336
DOI: 10.1021/jacs.0c06641 -
FASEB Journal : Official Publication of... Sep 2020Cancer cells rely on several metabolic pathways such as lipid metabolism to meet the increase in energy demand, cell division, and growth and successfully adapt to... (Review)
Review
Cancer cells rely on several metabolic pathways such as lipid metabolism to meet the increase in energy demand, cell division, and growth and successfully adapt to challenging environments. Fatty acid synthesis is therefore commonly enhanced in many cancer cell lines. Thus, relevant efforts are being made by the scientific community to inhibit the enzymes involved in lipid metabolism to disrupt cancer cell proliferation. We review the rapidly expanding body of inhibitors that target lipid metabolism, their side effects, and current status in clinical trials as potential therapeutic approaches against cancer. We focus on their molecular, biochemical and structural properties, selectivity and effectiveness and discuss their potential role as antitumor drugs.
Topics: Antineoplastic Agents; Azetidines; Dicarboxylic Acids; Enzyme Inhibitors; Fatty Acid Synthases; Fatty Acids; Humans; Lipid Metabolism; Lipogenesis; Neoplasms; Nitriles; Pyrazoles
PubMed: 32761847
DOI: 10.1096/fj.202000705R -
Molecular Pharmaceutics Aug 2022Acid-base multicomponent systems have become a popular choice as a strategy to fine-tune the physicochemical properties of active pharmaceutical ingredients. Current...
Acid-base multicomponent systems have become a popular choice as a strategy to fine-tune the physicochemical properties of active pharmaceutical ingredients. Current prediction tools based on the principles of anticrystal engineering cannot always accurately predict the nature of intermolecular interactions within a multicomponent system. Even small changes in the physicochemical parameters of parent components can result in unexpected outcomes, and many salt, cocrystal, and ionic liquid forms are still being discovered empirically. In this work, we aimed to establish structural consistency in a series of mixtures comprising lidocaine (LID) with decanedioic, undecanedioic, dodecanedioic, and tridecanedioic acids and to explore how length and flexibility of the acid carbon backbone affect the molecular recognition, crystallization, and thermal behavior of the expected binary systems. We found that neat grinding of LID with dicarboxylic acids results in the formation of eutectic phases. The observed eutectic melting points deviated from the ideal eutectic temperatures predicted by the Schroeder van Laar model because of hydrogen bonding between the reacting components within the mixtures. Furthermore, thermal and infrared analysis provided evidence for the possible formation of new phases stemming from partial ionization of the counterions. Besides, the structure of a previously undetermined form I of the tridecanedioic acid was solved by single crystal X-ray diffraction.
Topics: Crystallization; Dicarboxylic Acids; Hydrogen Bonding; Ionic Liquids; Lidocaine
PubMed: 35850530
DOI: 10.1021/acs.molpharmaceut.2c00381 -
Toxicological Sciences : An Official... Sep 2022Due to their endocrine disruption properties, phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) can affect the hormone-dependent development of the...
Gestational and Lactational Exposure to the Emergent Alternative Plasticizer 1,2-Cyclohexane Dicarboxylic Acid Diisononyl Ester (DINCH) Impairs Lipid Metabolism to a Greater Extent Than the Commonly Used Di(2-Ethylhexyl) Phthalate (DEHP) in the Adult Rat Mammary Gland.
Due to their endocrine disruption properties, phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) can affect the hormone-dependent development of the mammary gland. Over the past few years, DEHP has been partially replaced by 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) which also have potential endocrine disrupting properties. The goal of the present study is to understand the impact of a gestational and lactational exposure to DEHP and DINCH on mammary gland development using Sprague Dawley rats. Both plasticizers altered the adipocytes of the mammary gland fat pad of adult progeny, as demonstrated by a decrease in their size, folding of their membrane, and modulations of the lipid profiles. DEHP treatments decreased the expression of Rxrα and Scd1 at the low and high dose, respectively, but did not affect any of the other genes studied. DINCH modulation of lipid metabolism could be observed at puberty by a decreased expression of genes implicated in triglyceride synthesis, lipid transport, and lipolysis, but by an increased expression of genes of the β-oxidation pathway and of genes involved in lipid storage and fatty acid synthesis at adulthood, compared with control and DEHP-treated rats. A strong upregulation of different inflammatory markers was observed following DINCH exposure only. Together, our results indicate that a gestational and lactational exposure to DINCH has earlier and more significant effects on lipid homeostasis, adipogenesis, and the inflammatory state of the adult mammary gland than DEHP exposure. The long-term consequence of these effects on mammary gland health remained to be determined.
Topics: Animals; Cyclohexanes; Dicarboxylic Acids; Diethylhexyl Phthalate; Esters; Fatty Acids; Hormones; Lipid Metabolism; Lipids; Phthalic Acids; Plasticizers; Rats; Rats, Sprague-Dawley; Sexual Maturation; Triglycerides
PubMed: 35861430
DOI: 10.1093/toxsci/kfac076 -
Clinical Drug Investigation Jan 2021BACKGROUND AND OBJECTIVE: A limited number of trials have evaluated the efficacy of a fixed-dose combination of bempedoic acid and ezetimibe for the treatment of... (Meta-Analysis)
Meta-Analysis
UNLABELLED
BACKGROUND AND OBJECTIVE: A limited number of trials have evaluated the efficacy of a fixed-dose combination of bempedoic acid and ezetimibe for the treatment of hypercholesterolemia. The aim of this meta-analysis of existing studies was to evaluate the efficacy and safety of fixed-dose bempedoic acid and ezetimibe combination therapy for the treatment of hypercholesterolemia.
METHODS
A systematic literature search was conducted to identify randomized controlled trials (RCTs) comparing bempedoic acid and ezetimibe, versus placebo or ezetimibe alone, to 30 August 2020. A meta-analysis was conducted to investigate the efficacy of bempedoic acid and ezetimibe on lipid parameters and highly sensitive C-reactive protein (hsCRP) levels in patients with hypercholesterolemia or established atherosclerotic cardiovascular disease (ASCVD). Mean differences (MDs) or relative risk (RR) with their corresponding 95% confidence intervals (CIs), using random-effects models, were used to provide pooled estimates.
RESULTS
A total of three phase II and III RCTs, comprising 388 patients, of whom 49.2% were treated with bempedoic acid and ezetimibe, and 197 controls, were identified. The duration of treatment was 12 weeks. Bempedoic acid and ezetimibe significantly reduced low-density lipoprotein cholesterol (MD - 29.14%, 95% CI - 39.52 to - 18.76; p < .001), total cholesterol (MD - 15.78%, 95% CI - 20.84 to - 10.72; p = 0.01), non-high-density lipoprotein cholesterol (MD - 18.36%, 95% CI - 24.60 to - 12.12; p = 0.01), and hsCRP levels (MD - 30.48%, 95% CI - 44.69 to - 16.28; p = 0.04). No significant effects on triglycerides (MD - 8.35%, 95% CI - 16.08 to - 0.63; p = 0.72) and improvement in high-density lipoprotein cholesterol (MD 1.63%, 95% CI - 4.03 to 7.28; p = 0.92) were observed with the fixed-dose combination therapy. Regarding safety, bempedoic acid and ezetimibe combination was associated with a non-significant increased risk of drug-related adverse events (RR 1.61, 95% CI 0.86-2.35) and overall adverse events (RR 1.16. 95% CI 0.97-1.35); however, the incidence of discontinuation of therapy (RR 0.75, 95% CI 0.35-1.49) was lower.
CONCLUSION
This review found bempedoic acid and ezetimibe significantly lowered lipid parameters, attenuated hsCRP levels, and had an acceptable safety profile for the treatment of hypercholesterolemia and ASCVD.
Topics: Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dicarboxylic Acids; Drug Combinations; Ezetimibe; Fatty Acids; Humans; Hypercholesterolemia; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 33368025
DOI: 10.1007/s40261-020-00989-1 -
PloS One 2024Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for hypercholesterolemia. Nonetheless, the outcomes of the initial investigations might have been more definitive and coherent. Our objective was to perform a quantitative meta-analysis in order to evaluate bempedoic acid's safety and effectiveness.
METHODS
A search was conducted on ClinicalTrials.gov, and PubMed from the time of inception until September 28, 2023. Randomized controlled trials comparing the safety and efficacy of bempedoic acid among patients with statin intolerance and those without were included in our analysis. The trial outcomes were summarized using a random effects model and were provided as mean differences or odds ratios (ORs) with a confidence interval of 95%. Additionally, trial heterogeneity and the possibility of bias were evaluated and investigated.
RESULTS
Bempedoic acid treatment reduced low-density lipoprotein cholesterol levels more than placebo (mean difference -2.97%, 95% CI -5.89% to -0.05%), according to a pooled analysis of 16 eligible trials. The risk of death (OR 1.18, 95% CI 0.70 to 1.98) and muscle-associated occurrences (OR 1.00, 95% CI 0.77 to 1.31) was not impacted by bempedoic acid. In contrast, discontinuation of treatment was more frequently caused by adverse events in the bempedoic acid group (OR 1.13, 95% CI 1.01 to 1.27).
CONCLUSIONS
In patients with statin intolerance as well as those without, bempedoic acid is a safe and efficacious lipid-lowering agent, according to findings from randomized controlled trials.
Topics: Humans; Dicarboxylic Acids; Fatty Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Randomized Controlled Trials as Topic
PubMed: 38277431
DOI: 10.1371/journal.pone.0297854 -
Current Atherosclerosis Reports Aug 2022There have been recent developments of novel therapeutic agents for lipid lowering. This article reviews treatment concepts for two of the newest lipid-lowering... (Review)
Review
PURPOSE OF REVIEW
There have been recent developments of novel therapeutic agents for lipid lowering. This article reviews treatment concepts for two of the newest lipid-lowering medications.
RECENT FINDINGS
Bempedoic acid inhibits adenosine citrate lyase, decreasing intracellular lipogenesis. This oral medication is a prodrug and requires activation by enzymes present in hepatocytes but absent in the skeletal muscle. Clinical trials demonstrated additive benefit with statin therapy, and it was well tolerated in statin-intolerant populations. Inclisiran uses RNA interference to prevent translation of PCSK9 mRNA. Due to its stability, it can be given as an injection every 6 months and produces consistent, durable, and potent cholesterol lowering. Bempedoic acid and inclisiran represent new avenues of treatment for the prevention and treatment of cardiovascular disease. This will allow for more comprehensive care by addressing challenges with medication adherence, such as adverse effects to prior medications as well as ease of dosing.
Topics: Dicarboxylic Acids; Fatty Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; RNA, Small Interfering
PubMed: 35666408
DOI: 10.1007/s11883-022-01036-4