This review aims to be a comprehensive, authoritative, critical, and readable review of general interest to the medicinal chemistry community because it focuses on the pharmacological, chemical, ...structural and computational aspects of diverse chemical categories as monoamine oxidase inhibitors (MAOIs). Monoamine oxidases (MAOs), namely MAO-A and MAO-B represent an enormously valuable class of neuronal enzymes embodying neurobiological origin and functions, serving as potential therapeutic target in neuronal pharmacotherapy, and hence we have coined the term “Neurozymes” which is being introduced for the first time ever. Nowadays, therapeutic attention on MAOIs engrosses two imperative categories; MAO-A inhibitors, in certain mental disorders such as depression and anxiety, and MAO-B inhibitors, in neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD). The use of MAOIs declined due to some potential side effects, food and drug interactions, and introduction of other classes of drugs. However, curiosity in MAOIs is reviving and the recent developments of new generation of highly selective and reversible MAOIs, have renewed the therapeutic prospective of these compounds. The initial section of the review emphasizes on the detailed classification, structural and binding characteristics, therapeutic potential, current status and future challenges of the privileged pharmacophores. However, the chemical prospective of privileged scaffolds such as; aliphatic and aromatic amines, amides, hydrazines, azoles, diazoles, tetrazoles, indoles, azines, diazines, xanthenes, tricyclics, benzopyrones, and more interestingly natural products, along with their conclusive SARs have been discussed in the later segment of review. The last segment of the article encompasses some patents granted in the field of MAOIs, in a simplistic way.
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•This is a comprehensive review focusing on the pharmacological, chemical, and computational aspects of MAOIs.•We have coined the term “Neurozymes” for the MAOs, which is being introduced for the first time ever in this review.•Chemically diverse category of compounds having MAO inhibitory properties were compiled in this review.•The last section of the review gives an understanding of the patents granted on the MAOs and their inhibitors.
China's Communist Party seized power in 1949 after a long guerrilla insurgency followed by full-scale war, but the revolution was just beginning. Andrew Walder narrates the rise and fall of the ...Maoist state from 1949 to 1976--an epoch of startling accomplishments and disastrous failures, steered by many forces but dominated above all by Mao Zedong.
"The writings of Mao Zedong have been circulated throughout the world more widely, perhaps, than those of any other single person this century. The “Talks at the Yan’an Conference on Literature and ...Art” has occupied a prominent position among his many works and has been the subject of intense scrutiny both within and outside China. This text has undoubted importance to modern Chinese literature and history. In particular, it reveals Mao’s views on such questions as the relationship between writers or works of literature and their audience, or the nature and value of different kinds of literary products. In this translation and commentary, Bonnie S. McDougall finds that Mao was in fact ahead of many of his critics in the West and his Chinese contemporaries in his discussion of literary issues. Unlike the majority of modern Chinese writers deeply influenced by Western theories of literature and society (including Marxism), Mao remained close to traditional patterns of thought and avoided the often mechanical or narrowly literal interpretations that were the hallmark of Western schools current in China in the early twentieth century. Many of the detailed discussions on the “Talks” in the West have been concerned with their political and historical significance. However, since Mao is a literary figure of some importance in twentieth-century China, McDougall finds it worthwhile to follow up his published remarks on the nature and source of literature and the means of its evaluation. By better understanding the complex and revolutionary ideas contained in the “Talks,” McDougall suggests we may acquire the necessary analytical tools for a more fruitful investigation into contemporary Chinese literature."
Monoamine oxidase (MAO) is capable of catalysing the oxidative deamination of amines and neurotransmitters. MAO plays a pivotal role in maintaining neurotransmitters linked to neurological disorders ...viz. Alzheimer's disease (AD), Parkinson's disease (PD) etc. Therefore, inhibition of MAO can be implicated to the cure of such diseases. Synthetic MAO inhibitors are known to inhibit MAO activity. However, there are safety issues with synthetic MAO inhibitors and many of their effects are non-selective and irreversible. Contrasting synthetic drugs, plant-derived natural products have been popularized globally owing to their extensive acceptability and applicability, therapeutic potency and minimum side effects which potentiated the possibility of developing reversible, promising MAO inhibitors based on natural products. The present review comprehensively elucidates plant -derived natural reversible MAO inhibitors using the literature from the popular databases such as Google Scholar, Scopus, PubMed and Web of Science. This literature review reports approximately 51 plants that have been evaluated for MAO inhibitory activity. In addition, 93 plant-derived natural compounds were retrieved as MAO inhibitors. Majority of these investigations predominantly utilized an in vitro approach to evaluate the MAO inhibitors in relation to the developing treatments of related neurological diseases. However, in vivo studies and clinical trials are still lacking in evaluating the botanical-based MAO inhibitors. The aim of this review is to retrieve the recent literature to explore the in vitro and in vivo studies of plant-based natural products as MAO inhibitors, their structure-activity relationship and relevant molecular docking analyses and their roles in the emerging therapy against disorders like AD, and PD. Further, the review also discusses the shortcomings in the existing research in order to generate more coordinated and focused research in future.
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•Plant natural products acts as promising MAO-inhibitors.•They are capable of inhibiting both MAO-A and MAO-B.•MAO-inhibition is implicated to the treatment of many neurological diseases.•A number of in vitro and in vivo studies described MAO-inhibition by botanicals
Synthetic cannabinoid receptor agonists (SCRAs) are one of the fastest growing classes of recreational drugs. Despite their growth in use, their vast chemical diversity and rapidly changing landscape ...of structures make understanding their effects challenging. In particular, the side effects for SCRA use are extremely diverse, but notably include severe outcomes such as cardiac arrest. These side effects appear at odds with the main putative mode of action, as full agonists of cannabinoid receptors. We have hypothesized that SCRAs may act as MAO inhibitors, owing to their structural similarity to known monoamine oxidase inhibitors (MAOI's) as well as matching clinical outcomes (hypertensive crisis) of ‘monoaminergic toxicity’ for users of MAOIs and some SCRA use. We have studied the potential for SCRA‐mediated inhibition of MAO‐A and MAO‐B via a range of SCRAs used commonly in the UK, as well as structural analogues to prove the atomistic determinants of inhibition. By combining in silico and experimental kinetic studies we demonstrate that SCRAs are MAO‐A‐specific inhibitors and their affinity can vary significantly between SCRAs, most notably affected by the nature of the SCRA ‘head’ group. Our data allow us to posit a putative mechanism of inhibition. Crucially our data demonstrate that SCRA activity is not limited to just cannabinoid receptor agonism and that alternative interactions might account for some of the diversity of the observed side effects and that these effects can be SCRA‐specific.
We have studied the potential for SCRA‐mediated inhibition of MAO‐A and MAO‐B using a range of SCRAs used commonly in the UK, as well as structural analogues to prove the atomistic determinants of inhibition. By combining in silico and experimental kinetic studies, we demonstrate that SCRAs are MAO‐A‐specific inhibitors, and the affinity can vary significantly between SCRAs, with a mechanism posited.
What shaped the ideas and actions of one of the most influential leaders of the 20th century? Presenting a new account of Mao Zedong’s lifelong engagement with philosophy, Robert Allinson reveals the ...extent to which Chinese and Western thinkers determined Mao’s political career. For the first time Mao’s understanding of early philosophers such as Confucius, Laozi, Aristotle, Hegel, Schopenhauer and Nietzsche is looked at in close detail. Drawing upon his exposure as a student to both traditional Chinese and Western philosophy, Allinson shows how Mao’s reading of Marxism utilized concepts from the traditional Yijingto produce a philosophy that departs from Engels and the Soviet model. By revealing how Mao’s reading of Western political thought, as well as misreadings of traditional Chinese thought impacted his thinking, Allinson presents a fresh and challenging study of the man who ushered in anti-intellectualism during the dark period of the Cultural Revolution.
Mao Zedong's political career spanned more than half a century. The ideas he championed transformed one of the largest nations on earth and inspired revolutionary movements across the world. Even ...today Mao lives on in China, where he is regarded by many as a near-mythical figure, and in the West, where a burgeoning literature continues to debate his memory. In this book, leading scholars from different generations and around the world offer a critical evaluation of the life and legacy of China's most famous - some would say infamous - son. The book brings the scholarship on Mao up to date, and its alternative perspectives equip readers to assess for themselves the nature of this mercurial figure and his significance in modern Chinese history.
Ligands targeting tau for use with positron emission tomography have rapidly been developed during the past several years, enabling the in vivo study of tau pathology in patients with Alzheimer's ...disease and related non-Alzheimer's disease tauopathies. Several candidate compounds have been developed, showing good in vitro characteristics with respect to their ability to bind tau deposits; off-target binding, however, has also been observed. In this short commentary, we briefly summarize the available in vivo and in vitro evidence pertaining to their off-target binding and discuss the different approaches that are needed for the future development of tau positron emission tomography tracers.
A chemoenzymatic cascade process for the sustainable production of pyrroles has been developed. Pyrroles were synthesized by exploiting the previously unexplored aromatizing activity of monoamine ...oxidase enzymes (MAO-N and 6-HDNO). MAO-N/6-HDNO whole cell biocatalysts are able to convert 3-pyrrolines into pyrroles under mild conditions and in high yields. Moreover, MAO-N can work in combination with the ruthenium Grubbs catalyst, leading to the synthesis of pyrroles from diallylamines/-anilines in a one-pot cascade metathesis–aromatization sequence.
Based on archival materials from several countries, especially China, , interviews, and more than twenty years of research on the subject, Zhihua Shen and Yafeng Xia offer a comprehensive look at the ...Sino-Soviet alliance from the end of the World War II through 1959, when the alliance ended as a result of foreign and domestic policies. Mao and the Sino-Soviet Partnership, 1945-1959: A New History is a reevaluation of the history of this alliance and offers the first comprehensive account of it from a Chinese perspective.
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