Amide Bond Bioisosteres: Strategies, Synthesis, and Successes

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(21), P. 12290 - 12358

Published: July 20, 2020

The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed rational modification lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acquire novel chemical space secure intellectual property. introduction bioisostere leads structural changes molecular size, shape, electronic distribution, polarity, pKa, dipole or polarizability, which can be either favorable detrimental biological activity. This approach has opened up new avenues drug design development resulting more efficient candidates introduced onto market as well clinical pipeline. Herein, we review strategic decisions selecting an (the why), synthetic routes each how), success stories implementation) provide comprehensive overview this important toolbox for medicinal chemists.

Language: Английский

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Role of sleep deprivation in immune-related disease risk and outcomes

Communications Biology, Journal Year: 2021, Volume and Issue: 4(1)

Published: Nov. 18, 2021

Modern societies are experiencing an increasing trend of reduced sleep duration, with nocturnal sleeping time below the recommended ranges for health. Epidemiological and laboratory studies have demonstrated detrimental effects deprivation on Sleep exerts immune-supportive function, promoting host defense against infection inflammatory insults. has been associated alterations innate adaptive immune parameters, leading to a chronic state increased risk infectious/inflammatory pathologies, including cardiometabolic, neoplastic, autoimmune neurodegenerative diseases. Here, we review recent advancements responses as evidenced by experimental epidemiological studies, pathophysiology, role deprivation-induced changes in Gaps knowledge methodological pitfalls still remain. Further understanding causal relationship between deregulation would help identify individuals at disease prevent adverse health outcomes.

Language: Английский

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Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease

Biomolecules, Journal Year: 2020, Volume and Issue: 10(9), P. 1211 - 1211

Published: Aug. 20, 2020

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are great importance in preserving body functions homeostasis, with impact peripartum period adult life. Melatonin promotes adaptation through allostasis stands out as an endogenous, dietary, therapeutic molecule important health benefits. The effects intertwined exerted throughout pregnancy later during development aging. supplementation can reduce ischemia-induced oxidative damage fetal brain, increase offspring survival inflammatory states, blood pressure offspring. In adulthood, disturbances production negatively progression cardiovascular risk factors promote neurodegenerative diseases. most studied linked to hypertension myocardial ischemia/reperfusion injury, while promising ones regaining control metabolic syndrome components. addition, there might be emerging role for adjuvant treating coronavirus disease 2019 (COVID 19). present review summarizes comments on data regarding roles by homeostasis stress inflammation related pathologies.

Language: Английский

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The neuroprotective role of melatonin in neurological disorders

Journal of Neuroscience Research, Journal Year: 2018, Volume and Issue: 96(7), P. 1136 - 1149

Published: March 1, 2018

Melatonin is a neurohormone secreted from the pineal gland and has wide-ranging regulatory neuroprotective role. It been reported that melatonin level disturbed in some neurological conditions such as stroke, Alzheimer's disease, Parkinson's which indicates its involvement pathophysiology of these diseases. Its properties qualify it to be promising potential therapeutic agent, with no side effects, for disorders. This review discusses localizes effect

Language: Английский

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Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1135 - 1135

Published: Feb. 8, 2020

Melatonin is probably produced in all cells but only secreted by the pineal gland. The secretion of melatonin determined light–dark cycle, and it released at night. regulates biological rhythms via its receptors located suprachiasmatic nuclei hypothalamus. also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). direct radical scavenging actions are receptor independent. ROS play an important role reproductive function including ovulatory process. However, excessive can have adverse effect on oocytes because oxidative stress, thereby causing infertility. It becoming clear that ovarian follicular fluid themselves, which protects these from damage well having other beneficial oocyte maturation, fertilization, embryo development. Trials humans investigated improvement outcomes assisted technology (ART), vitro fertilization transfer (IVF-ET), way administering patients suffering In addition, clinical research examined anti-aging molecule antioxidative actions, relationship with aging diseases, e.g., Alzheimer’s Parkinson’s disease, underway. may reduce aging, a major issue technology. This review explains between human function, applications expected improve IVF, while discussing possibilities for preventing aging.

Language: Английский

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Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti‐inflammatory phenotype through STAT3 pathway

CNS Neuroscience & Therapeutics, Journal Year: 2019, Volume and Issue: 25(12), P. 1353 - 1362

Published: Dec. 1, 2019

Microglia and infiltrated macrophages play important roles in inflammatory processes after ischemic stroke. Modulating microglia/macrophage polarization from pro-inflammatory phenotype to anti-inflammatory state has been suggested as a potential therapeutic approach the treatment of Melatonin shown be neuroprotective experimental stroke models. However, effect melatonin on microglia underlying mechanisms remain unknown.In vivo, cerebral ischemia was induced by distal middle artery occlusion (dMCAO) C57BL/6J mice. injected intraperitoneally (20 mg/kg) at 0 24 hours ischemia. In vitro, microglial cell line BV2 stimulated with conditioned media (CM) collected oxygen-glucose deprivation (OGD) challenged neuronal Neuro-2a (N2a). Real-time PCR utilized detect mRNA expression markers. Activation signal transducer activator transcription 3 (STAT3) pathway determined Western blot phosphorylated STAT3 (pSTAT3). A neuron-microglia co-culture system used determine whether can inhibit neurotoxic post-OGD neurons.Melatonin reduced brain infarct improved neurological functions days dMCAO, which accompanied decreased markers increased brain. vitro studies confirmed that directly inhibited responses cells upon exposure OGD neuron CM. The possessing exacerbated N2a death, whereas such effect. Further, enhanced otherwise pSTAT3 treated blockade significantly shift.Melatonin ameliorates damage least partially through shifting polarity STAT3-dependent manner.

Language: Английский

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Phytomelatonin: an unexpected molecule with amazing performances in plants

Journal of Experimental Botany, Journal Year: 2022, Volume and Issue: 73(17), P. 5779 - 5800

Published: Jan. 12, 2022

Phytomelatonin, a multifunctional molecule that has been found to be present in all plants examined date, an important role as modulatory agent (a biostimulator) improves plant tolerance both biotic and abiotic stress. We review of phytomelatonin considers its roles metabolism particular interactions with hormone network. In the primary plants, melatonin rate efficiency photosynthesis, well related factors such stomatal conductance, intercellular CO2, Rubisco activity. It also shown down-regulate some senescence transcription factors. Melatonin up-regulates many enzyme transcripts carbohydrates (including sucrose starch), amino acids, lipid metabolism, optimizing N, P, S uptake. With respect secondary clear increases polyphenol, glucosinolate, terpenoid, alkaloid contents have described numerous melatonin-treated plants. Generally, most genes these biosynthesis pathways up-regulated by melatonin. The great regulatory capacity is result control redox networks. acts master regulator, up-/down-regulating different levels signalling, key player homeostasis. counteract diverse critical situations pathogen infections stresses, provide varying degrees tolerance. propose possible future applications for crop improvement post-harvest product preservation.

Language: Английский

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Oxidative stress, the blood–brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(10), P. 3988 - 4024

Published: July 16, 2023

In recent years, growing awareness of the role oxidative stress in brain health has prompted antioxidants, especially dietary to receive attention as possible treatments strategies for patients with neurodegenerative diseases (NDs). The most widely studied antioxidants include active substances such vitamins, carotenoids, flavonoids and polyphenols. Dietary are found usually consumed foods fresh fruits, vegetables, nuts oils gaining popularity due recently their potential preventive protective agents against NDs, well abundant natural sources, generally non-toxic nature, ease long-term consumption. This review article examines development explores ‘two-sidedness’ blood–brain barrier (BBB) a nervous system an impeding use drug medicinal products and/or supplements prevention therapy reviews BBB permeability common suplements efficacy treatment NDs. Finally, current challenges future directions NDs using discussed, useful information on is provided.

Language: Английский

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G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 3, 2023

Neuropsychiatric disorders are multifactorial with diverse aetiological factors. Identifying treatment targets is challenging because the diseases resulting from heterogeneous biological, genetic, and environmental Nevertheless, increasing understanding of G protein-coupled receptor (GPCR) opens a new possibility in drug discovery. Harnessing our knowledge molecular mechanisms structural information GPCRs will be advantageous for developing effective drugs. This review provides an overview role various neurodegenerative psychiatric diseases. Besides, we highlight emerging opportunities novel GPCR address recent progress development.

Language: Английский

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Therapeutic potential of melatonin related to its role as an autophagy regulator: A review

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 66(1)

Published: Oct. 17, 2018

There are several pathologies, syndromes, and physiological processes in which autophagy is involved. This process of self-digestion that cells trigger as a survival mechanism complex tightly regulated, according to the homeostatic conditions organ. However, all cases, its relationship with oxidative stress alterations evident, following pathway suggests endoplasmic reticulum and/or mitochondrial changes. accumulating evidence beneficial role melatonin has regulation restoration damaged autophagic processes. In this review, we focus on major changes such aging essential pathologies including cancer, neurodegenerative diseases, viral infections obesity, document each these different situations.

Language: Английский

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