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Narayan D. Chaurasiya Francisco Leon Ilias Muhammad Babu L. Tekwani 《Molecules (Basel, Switzerland)》2022,27(13)
Monoamine oxidase inhibitors (MAOIs) are an important class of drugs prescribed for treatment of depression and other neurological disorders. Evidence has suggested that patients with atypical depression preferentially respond to natural product MAOIs. This review presents a comprehensive survey of the natural products, predominantly from plant sources, as potential new MAOI drug leads. The psychoactive properties of several traditionally used plants and herbal formulations were attributed to their MAOI constituents. MAO inhibitory constituents may also be responsible for neuroprotective effects of natural products. Different classes of MAOIs were identified from the natural product sources with non-selective as well as selective inhibition of MAO-A and -B. Selective reversible natural product MAOIs may be safer alternatives to the conventional MAOI drugs. Characterization of MAO inhibitory constituents of natural products traditionally used as psychoactive preparations or for treatment of neurological disorders may help in understanding the mechanism of action, optimization of these preparations for desired bioactive properties, and improvement of the therapeutic potential. Potential therapeutic application of natural product MAOIs for treatment of neuroblastoma is also discussed. 相似文献
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Open innovation initiatives provide opportunities for collaboration and sharing of knowledge and experience between industry, academia, and government institutions. Through open innovation, Merck is offering a Mini Library of 80 carefully selected compounds from previous research and development projects to a broader scientific community for testing in academic drug discovery projects. These compounds are predominantly drug-like and cover a broad range of molecular targets. They could potentially interact with other enzymes, receptors, transporters, and ion channels of interest. The Mini Library was tested on seven in-house enzymes (bacterial MurA, MurC ligase, and DdlB enzyme, human MAO-A/B, human BChE, and murine AChE), and several hits were identified. A follow-up series of structural analogues provided by Merck gave a more detailed insight into the accessibility and the quality of the hit compounds. For example, sartan derivatives were moderate inhibitors of MurC, whereas bisarylureas were potent, selective, nanomolar inhibitors of hMAO-B. Importantly, 3-n-butyl-substituted indoles were identified as low nanomolar selective inhibitors of hBChE. All in all, the hit derivatives provide new starting points for the further exploration of the chemical space of high-quality enzyme inhibitors. 相似文献
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Lung cancer is one of the most common causes of cancer-related deaths worldwide. Monoamine Oxidase-A (MAO-A) enzyme mediates the production of reactive oxygen species (ROS) that trigger DNA damage and oxidative injury of cells resulting in tumor initiation and progression. Available MAO-A inhibitors are used as antidepressants, however, their role as anticancer agents is still under investigation. Ligand- and structure-based drug design approaches guided the discovery and development of novel MAO-A inhibitors. A series of 1H indole-2-carboxamide derivatives was prepared and characterized using 1H-NMR, 13C-NMR, and IR. The antiproliferative effects of MAO-A inhibitors were evaluated using the cell viability assay (MTT), and MAO-A activity was evaluated using MAO-A activity assay. The presumed inhibitors significantly inhibited the growth of lung cell lines in a dose- and time dependent manner. The half maximal inhibitory concentration (IC50) values of MAO-A inhibitors (S1, S2, S4, S7, and S10) were 33.37, 146.1, 208.99, 307.7, and 147.2 µM, respectively, in A549. Glide docking against MAO-A showed that the derivatives accommodate MAO-A binding cleft and engage with key binding residues. MAO-A inhibitors provide significant and consistent evidence on MAO-A activity in lung cancer and present a potential target for the development of new chemotherapeutic agents. 相似文献
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