1,721,050 research outputs found
Inhibition of PPARγ by Natural Compounds as a Promising Strategy in Obesity and Diabetes
Full text linkA wide group of natural compounds (flavonoids, stilbenes, neolignans and others) has been identified as Peroxisome Proliferator-Activated Receptor (PPAR) agonists, with a large variety of chemical structure and different activity versus the three PPAR subtypes. These receptors are transcription factors controlling metabolic pathways in the organism, involved in lipid and glucose metabolism, cell differentiation and energy homeostasis. Otherwise, very little is known about natural compounds able to inhibit PPARs. A number of studies demonstrate that PPARγ repression has a beneficial effect in reducing body weight and improving insulin sensitivity, suggesting a potential clinical role in obesity and type 2 diabetes. This review analyzes natural compounds able to repress PPAR activity and their potential use in metabolic disorders. © 2019 Ammazzalorso and Amoroso
Recent trends and challenges to overcome Pseudomonas aeruginosa infections
No full textIntroduction: Pseudomonas aeruginosa (PA) is a Gram-negative bacterium that can cause a wide range of severe infections in immunocompromised patients. The most difficult challenge is due to its ability to rapidly develop multi drug-resistance. New strategies are urgently required to improve the outcome of patients with PA infections. The present patent review highlights the new molecules acting on different targets involved in the antibiotic resistance. Area covered: This review offers an insight into new potential PA treatment disclosed in patent literature. From a broad search of documents claiming new PA inhibitors, we selected and summarized molecules that showed in vitro and in vivo activity against PA spp. in the period 2020 and 2023. We collected the search results basing on the targets explored. Expert opinion: This review examined the main patented compounds published in the last three years, with regard to the structural novelty and the identification of innovative targets. The main areas of antibiotic resistance have been explored. The compounds are structurally unrelated to earlier antibiotics, characterized by a medium-high molecular weight and the presence of heterocycle rings. Peptides and antibodies have also been reported as potential alternatives to chemical treatment, hereby expanding the therapeutic possibilities in this field
Peroxisome Proliferator-Activated Receptor agonists and antagonists: an updated patent review (2020–2023)
No full textIntroduction: The search for novel compounds targeting Peroxisome Proliferator-Activated Receptors (PPARs) is currently ongoing, starting from the previous successfully identification of selective, dual or pan agonists. In last years, researchers' efforts are mainly paid to the discovery of PPARγ and δ modulators, both agonists and antagonists, selective or with a dual-multitarget profile. Some of these compounds are currently under clinical trials for the treatment of primary biliary cirrhosis, nonalcoholic fatty liver disease, hepatic, and renal diseases. Areas covered: A critical analysis of patents deposited in the range 2020-2023 was carried out. The novel compounds discovered were classified as selective PPAR modulators, dual and multitarget PPAR agonists. The use of PPAR ligands in combination with other drugs was also discussed, together with novel therapeutic indications proposed for them. Expert opinion: From the analysis of the patent literature, the current emerging landscape sees the necessity to obtain PPAR multitarget compounds, with a balanced potency on three subtypes and the ability to modulate different targets. This multitarget action holds great promise as a novel approach to complex disorders, as metabolic, inflammatory diseases, and cancer. The utility of PPAR ligands in the immunotherapy field also opens an innovative scenario, that could deserve further applications
Synthesis of diastereomerically enriched 2-bromoesters and their reaction with nucleophiles
No full text-2-Bromoesters enriched in the (S,R)-diastereoisomer can be easily pre pared by coupling of racemic 2-bromoacids with (R)-pantolactone. Displacement of the bromine atom with nucleophiles, under suitable reaction conditions, occurs without epimerization of starting compounds, giving (R,R)-2-substituted carboxylic acid derivatives
Multitarget PPARγ agonists as innovative modulators of the metabolic syndrome
No full textA multitarget pharmacologic approach could be advantageous for the therapy of metabolic multiple diseases, such as the metabolic syndrome, which is characterized by metabolic abnormalities associated with diabetes, obesity, hypertension, and increased cardiovascular risk. PPAR receptors play a critical role in metabolic disorders, affecting glucose and lipid metabolism. Drugs simultaneously targeting PPAR and other validated metabolic targets, represent a promising multitarget approach to combine antihyperglycemic, antihyperlipidemic, and antihypertensive effects. This review offers a survey of recently developed multitarget PPARγ agonists as antidiabetic and antihypertensive drugs
A Review of Strategies for the Development of Alkyl Prolines in Drug Discovery
No full textAmong all natural α-amino acids, proline represents a singularity. Due to the presence of the pyrrolidine ring, proline includes a secondary amino group, that does not contain a hydrogen atom when involved in an amide bond. A variety of synthetic analogues have been developed in the last years, based on ring substitutions, incorporation of heteroatoms into the ring, expansion or contraction of the pyrrolidine ring. The present review focuses on chemical synthesis of mono substituted derivatives of proline containing leucine, isoleucine, valine side chains, and other alkyls, including the contribution of literature from 2004 to 2015 or earlier where necessary
Asymmetric synthesis of enantiomerically enriched chiral fibrates, thiols and aminoacids
No full textStilbene derivatives as new perspective in antifungal medicinal chemistry
No full textThe high incidence and mortality of invasive fungal infections and serious drug resistance have become a global public health issue. There is an urgent need for alternative antimicrobials to control fungal infections and targeting it by antifungal substances from the natural sources represents a promising new strategy for the development of novel antifungal agents. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a phytoalexin produced by plant species in response to environmental stress or pathogenic attacks. It has many known and potential therapeutic applications in human general homeostasis; it mediates a great number of biological responses relevant for human health such as anticancer, cardio and neuroprotective, antioxidant, and antimicrobial activities. Resveratrol is a natural antifungal agent, therefore it can be considered as a scaffold for designing structural relatives potentially capable of mediating more intense responses in a more specific way. Also, stilbenes produced by several plants may be useful lead structure for the chemical synthesis of antifungal. Their antifungal potential represents a useful solution to the drug resistance and side effect complications that occur after pharmacological treatment of infectious diseases. The purpose of this review is to present an overview on resveratrol derivatives, both natural and synthetic, with antifungal activity and summarize the chemical structure and the therapeutic versatility of stilbene-containing compounds
Blocking the Peroxisome Proliferator‐Activated Receptor (PPAR): An Overview
No full textPeroxisome proliferator-activated receptors (PPARs) have been studied extensively over the last few decades and have been assessed as molecular targets for the development of drugs against metabolic disorders. A rapid increase in understanding of the physiology and pharmacology of these receptors has occurred, together with the identification of novel chemical structures that are able to activate the various PPAR subtypes. More recent evidence suggests that moderate activation of these receptors could be favorable in pathological situations due to a decrease in the side effects brought about by PPAR agonists. PPAR partial agonists and antagonists are interesting tools that are currently used to better elucidate the biological processes modulated by this family of nuclear receptors. Herein we present an overview of the various molecular structures that are able to block each of the PPAR subtypes, with a focus on promising therapeutic applications
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