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International Journal of Molecular... Mar 2022Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to...
Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol β-amino alcohol and β-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three β-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.
Topics: Alcohols; Amino Alcohols; Antineoplastic Agents; Apoptosis; Clove Oil; Eugenol; Humans
PubMed: 35409123
DOI: 10.3390/ijms23073759 -
Critical Care (London, England) Mar 2023The Chain of Survival highlights the effectiveness of early recognition of cardiac arrest and call for help, early cardiopulmonary resuscitation and early... (Review)
Review
The Chain of Survival highlights the effectiveness of early recognition of cardiac arrest and call for help, early cardiopulmonary resuscitation and early defibrillation. Most patients, however, remain in cardiac arrest despite these interventions. Drug treatments, particularly the use of vasopressors, have been included in resuscitation algorithms since their inception. This narrative review describes the current evidence base for vasopressors and reports that adrenaline (1 mg) is highly effective at achieving return of spontaneous circulation (number needed to treat 4) but is less effective on long-term outcomes (survival to 30 days, number needed to treat 111) with uncertain effects on survival with a favourable neurological outcome. Randomised trials evaluating vasopressin, either as an alternative to or in addition to adrenaline, and high-dose adrenaline have failed to find evidence of improved long-term outcomes. There is a need for future trials to evaluate the interaction between steroids and vasopressin. Evidence for other vasopressors (e.g. noradrenaline, phenylephedrine) is insufficient to support or refute their use. The use of intravenous calcium chloride as a routine intervention in out of hospital cardiac arrest is not associated with benefit and may cause harm. The optimal route for vascular access between peripheral intravenous versus intraosseous routes is currently the subject of two large randomised trials. Intracardiac, endobronchial, and intramuscular routes are not recommended. Central venous administration should be limited to patients where an existing central venous catheter is in situ and patent.
Topics: Humans; Epinephrine; Heart; Norepinephrine; Out-of-Hospital Cardiac Arrest; Vasoconstrictor Agents; Heart Arrest
PubMed: 36864469
DOI: 10.1186/s13054-023-04301-3 -
Advances in Experimental Medicine and... 2022Sphingosine 1-phosphate (S1P) is a well-defined bioactive lipid molecule derived from membrane sphingolipid metabolism. In the past decades, a series of key enzymes...
Sphingosine 1-phosphate (S1P) is a well-defined bioactive lipid molecule derived from membrane sphingolipid metabolism. In the past decades, a series of key enzymes involved in generation of S1P have been identified and characterized in detail, as well as enzymes degrading S1P. S1P requires transporter to cross the plasma membrane and carrier to deliver to its cognate receptors and therefore transduces signaling in autocrine, paracrine, or endocrine fashions. The essential roles in regulation of development, metabolism, inflammation, and many other aspects of life are mainly executed when S1P binds to receptors provoking the downstream signaling cascades in distinct cells. This chapter will review the synthesis, degradation, transportation, and signaling of S1P and try to provide a comprehensive view of the biology of S1P, evoking new enthusiasms and ideas into the field of the fascinating S1P.
Topics: Lysophospholipids; Signal Transduction; Sphingosine
PubMed: 35503175
DOI: 10.1007/978-981-19-0394-6_6 -
Microbial Pathogenesis Jul 2023Human microbiome interact reciprocally with the host. Recent findings showed the capability of microorganisms to response towards host signaling molecules, such as... (Review)
Review
Human microbiome interact reciprocally with the host. Recent findings showed the capability of microorganisms to response towards host signaling molecules, such as hormones. Studies confirmed the complex response of bacteria in response to hormones exposure. These hormones impact many aspects on bacteria, such as the growth, metabolism, and virulence. The effects of each hormone seem to be species-specific. The most studied hormones are cathecolamines also known as stress hormones that consists of epinephrine, norepinephrine and dopamine. These hormones affect the growth of bacteria either inhibit or enhance by acting like a siderophore. Epinephrine and norepinephrine have also been reported to activate QseBC, a quorum sensing in Gram-negative bacteria and eventually enhances the virulence of pathogens. Other hormones were also reported to play a role in shaping human microbiome composition and affect their behavior. Considering the complex response of bacteria on hormones, it highlights the necessity to take the impact of hormones on bacteria into account in studying human health in relation to human microbiome.
Topics: Humans; Norepinephrine; Epinephrine; Bacteria; Quorum Sensing; Hormones
PubMed: 37119938
DOI: 10.1016/j.micpath.2023.106125 -
Molecules (Basel, Switzerland) Oct 2021A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully...
A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.
Topics: Amino Alcohols; Animals; Apoptosis; Cell Survival; Cells, Cultured; Eugenol; Humans; Insecticides; Models, Molecular; Molecular Structure; Spodoptera
PubMed: 34771025
DOI: 10.3390/molecules26216616 -
Profiles of Drug Substances,... 2021The present study describes a comprehensive profile of Bisoprolol including detailed nomenclature; formulae, elemental analysis, appearance, its uses, applications, and...
The present study describes a comprehensive profile of Bisoprolol including detailed nomenclature; formulae, elemental analysis, appearance, its uses, applications, and methods for the preparation are outlined. The profile contains physicochemical properties of Bisoprolol including pKa value, solubility, X-ray powder diffraction, and methods of analysis (including compendial, electrochemical, spectroscopic, chromatographic and capillary electrophoresis). The study also covers thermal analysis such as differential scanning calorimetry and thermogravimetry of Bisoprolol. Which gives a brief idea of melting point, glass transition as well as differentiation between anhydrous and hydrated forms. In addition to these functional groups and structural confirmation of bisoprolol also presented with the help of Fourier transform infrared spectrometry and nuclear magnetic resonance spectroscopy, respectively. The mass fragmentation pattern of bisoprolol fumarate was reported using the electrospray ionization technique. Some recently reported methods for pharmacokinetic analysis of bisoprolol using high-performance liquid chromatography as well as liquid chromatography-mass spectrometry were also included in the study.
Topics: Bisoprolol; Chromatography, High Pressure Liquid; Drug Stability; Mass Spectrometry; Nuclear Magnetic Resonance, Biomolecular; Solubility; Spectroscopy, Fourier Transform Infrared
PubMed: 33461700
DOI: 10.1016/bs.podrm.2020.07.006 -
Chemical & Pharmaceutical Bulletin 2021Catalytic chemoselective reactions of innately less reactive functionalities over more reactive functionalities are described. A cooperative catalyst comprising a soft... (Review)
Review
Catalytic chemoselective reactions of innately less reactive functionalities over more reactive functionalities are described. A cooperative catalyst comprising a soft Lewis acid/hard Brønsted base enabled chemoselective activation of a hydroxyl group over an amino group, allowing for nucleophilic addition to electron-deficient olefins. The reaction could be applicable for a variety of amino alcohols, including pharmaceuticals, without requiring a tedious protection-deprotection process. Chemoselective enolization and subsequent α-functionalization of carboxylic acid derivatives were also achieved by a redox active catalyst through the radical process, providing unnatural α-amino/hydroxy acid derivatives bearing a complex carbon framework and a diverse set of functionalities. The present chemoselective catalysis described herein offers new opportunities to expand the chemical space for innovative drug discovery research.
Topics: Alkenes; Amino Alcohols; Carboxylic Acids; Catalysis; Drug Development; Lewis Acids; Molecular Structure
PubMed: 34078797
DOI: 10.1248/cpb.c21-00092 -
The Cochrane Database of Systematic... Dec 2023Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme... (Review)
Review
BACKGROUND
Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme deficiency; people with late-onset Pompe disease (LOPD) retain some residual enzyme activity. GAA deficiency is treated with an intravenous infusion of recombinant human acid alglucosidase alfa, an enzyme replacement therapy (ERT). Alglucosidase alfa and avalglucosidase alfa are approved treatments, but cipaglucosidase alfa with miglustat is not yet approved.
OBJECTIVES
To assess the effects of enzyme replacement therapies in people with late-onset Pompe disease.
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched MEDLINE OvidSP, clinical trial registries, and the reference lists of relevant articles and reviews. Date of last search: 21 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of ERT in people with LOPD of any age.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias and the certainty of the evidence (using GRADE). We resolved disagreements through discussion and by consulting a third author.
MAIN RESULTS
We included six trials (358 randomised participants) lasting from 12 to 78 weeks. A single trial reported on each comparison listed below. None of the included trials assessed two of our secondary outcomes: need for respiratory support and use of a walking aid or wheelchair. Certainty of evidence was most commonly downgraded for selective reporting bias. Alglucosidase alfa versus placebo (90 participants) After 78 weeks, alglucosidase alfa probably improves the six-minute walk test (6MWT) distance compared to placebo (mean difference (MD) 30.95 metres, 95% confidence interval (CI) 7.98 to 53.92; moderate-certainty evidence) and probably improves respiratory function, measured as the change in per cent (%) predicted forced vital capacity (FVC) (MD 3.55, 95% CI 1.46 to 5.64; moderate-certainty evidence). There may be little or no difference between the groups in occurrence of infusion reactions (risk ratio (RR) 1.21, 95% CI 0.57 to 2.61; low-certainty evidence), quality of life physical component score (MD -1.36 points, 95% CI -5.59 to 2.87; low-certainty evidence), or adverse events (RR 0.94, 95% CI 0.64 to 1.39; low-certainty evidence). Alglucosidase alfa plus clenbuterol versus alglucosidase alfa plus placebo (13 participants) The evidence is very uncertain about the effect of alglucosidase alfa plus clenbuterol compared to alglucosidase alfa plus placebo on: change in 6MWT distance after 52 weeks (MD 34.55 metres, 95% CI-10.11 to 79.21; very low-certainty evidence) and change in % predicted FVC (MD -13.51%, 95% CI -32.44 to 5.41; very low-certainty evidence). This study did not measure infusion reactions, quality of life, and adverse events. Alglucosidase alfa plus albuterol versus alglucosidase alfa plus placebo (13 participants) The evidence is very uncertain about the effect of alglucosidase alfa plus albuterol compared to alglucosidase alfa plus placebo on: change in 6MWT distance after 52 weeks (MD 30.00 metres, 95% CI 0.55 to 59.45; very low-certainty evidence), change in % predicted FVC (MD -4.30%, 95% CI -14.87 to 6.27; very low-certainty evidence), and risk of adverse events (RR 0.67, 95% CI 0.38 to 1.18; very low-certainty evidence). This study did not measure infusion reactions and quality of life. VAL-1221 versus alglucosidase alfa (12 participants) Insufficient information was available about this trial to generate effect estimates measured at one year or later. Compared to alglucosidase alfa, VAL-1221 may increase or reduce infusion-associated reactions at three months, but the evidence is very uncertain (RR 2.80, 95% CI 0.18 to 42.80). This study did not measure quality of life and adverse events. Cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo (125 participants) Compared to alglucosidase alfa plus placebo, cipaglucosidase alfa plus miglustat may make little or no difference to: 6MWT distance at 52 weeks (MD 13.60 metres, 95% CI -2.26 to 29.46); infusion reactions (RR 0.94, 95% CI 0.49 to 1.80); quality of life scores for physical function (MD 1.70, 95% CI -2.13 to 5.53) and fatigue (MD -0.30, 95% CI -2.76 to 2.16); and adverse effects potentially related to treatment (RR 0.83, 95% CI 0.49 to 1.40) (all low-certainty evidence). Cipaglucosidase alfa plus miglustat probably improves % predicted FVC compared to alglucosidase alfa plus placebo (MD 3.10%, 95% CI 1.04 to 5.16; moderate-certainty evidence); however, it may make little or no change in % predicted sniff nasal inspiratory pressure (MD -0.06%, 95% CI -8.91 to 7.71; low-certainty evidence). Avalglucosidase alfa versus alglucosidase alfa (100 participants) After 49 weeks, avalglucosidase alfa probably improves 6MWT compared to alglucosidase alfa (MD 30.02 metres, 95% CI 1.84 to 58.20; moderate-certainty evidence). Avalglucosidase alfa probably makes little or no difference to % predicted FVC compared to alglucosidase alfa (MD 2.43%, 95% CI -0.08 to 4.94; moderate-certainty evidence). Avalglucosidase alfa may make little or no difference to infusion reactions (RR 0.78, 95% CI 0.42 to 1.45), quality of life (MD 0.77, 95% CI -2.09 to 3.63), or treatment-related adverse events (RR 0.92, 95% CI 0.61 to 1.40), all low-certainty evidence.
AUTHORS' CONCLUSIONS
One trial compared the effect of ERT to placebo in LOPD, showing that alglucosidase alfa probably improves 6MWT and respiratory function (both moderate-certainty evidence). Avalglucosidase alfa probably improves 6MWT compared with alglucosidase alfa (moderate-certainty evidence). Cipaglucosidase plus miglustat probably improves FVC compared to alglucosidase alfa plus placebo (moderate-certainty evidence). Other trials studied the adjunct effect of clenbuterol and albuterol along with alglucosidase alfa, with little to no evidence of benefit. No significant rise in adverse events was noted with all ERTs. The impact of ERT on some outcomes remains unclear, and longer RCTs are needed to generate relevant information due to the progressive nature of LOPD. Alternative resources, such as post-marketing registries, could capture some of this information.
Topics: Humans; Glycogen Storage Disease Type II; Enzyme Replacement Therapy; Clenbuterol; Albuterol
PubMed: 38084761
DOI: 10.1002/14651858.CD012993.pub2 -
Chemical Communications (Cambridge,... Feb 2022Herein, a new strategy for the direct synthesis of functionalized pyrroles from β-amino alcohols and ynones ruthenium-catalyzed acceptorless dehydrogenative coupling...
Herein, a new strategy for the direct synthesis of functionalized pyrroles from β-amino alcohols and ynones ruthenium-catalyzed acceptorless dehydrogenative coupling has been demonstrated. This developed methodology proceeds in an atom- and step-economic fashion together with the merits of broad substrate scope, operational simplicity, and water and hydrogen gas as the sole by-products, which provides an alternative and sustainable way to access functionalized pyrroles. Further, this method was applied to the rapid synthesis of the COX-1/COX-2 inhibitor and boron dipyrromethene derivative successfully.
Topics: Amino Alcohols; Catalysis; Hydrogenation; Ketones; Molecular Structure; Pyrroles; Ruthenium
PubMed: 35080540
DOI: 10.1039/d1cc07018e -
Clinics in Dermatology 2023Chronic stress is an inextricable part of modern daily living; practically all human diseases, particularly cancer, are negatively affected by it. Numerous studies have...
Chronic stress is an inextricable part of modern daily living; practically all human diseases, particularly cancer, are negatively affected by it. Numerous studies have shown that stressors, depression, social isolation, and adversity correlate with a worse prognosis for patients with cancer, with increased symptoms, early metastasis, and a shortened life span. Prolonged or very intense adverse life episodes are perceived and assessed by the brain and translated into physiologic responses mediated through relays to the hypothalamus and locus coereleus. This response triggers the activation of the hypothalamus-pituitary-adrenal axis (HPA) and the peripheral nervous system (PNS) with the secretion of glucocorticosteroids/epinephrine and norepinephrine (NE). These hormones and neurotransmitters affect immune surveillance and the immune response to malignancies by skewing immunity from a type 1 to a type 2 response; this process not only impedes the detection and killing of cancer cells but induces immune cells to facilitate cancer growth and systemic spread. It may be mediated by the engagement of norepinephrine to β-adrenergic receptors, which can be partially reversed by the administration of β-blockers.
Topics: Humans; Norepinephrine; Epinephrine; Hypothalamo-Hypophyseal System; Neoplasms; Stress, Psychological
PubMed: 36882133
DOI: 10.1016/j.clindermatol.2023.03.008