Deciphering the detailed structure–activity relationship of coumarins as Monoamine oxidase enzyme inhibitors—An updated review

Koyiparambath, Vishal Payyalot; Rajappan, Krishnendu Prayaga; Rangarajan, T. M.; Al‐Sehemi, Abdullah G.; Pannipara, Mehboobali; Bhaskar, Vaishnav; Nair, Aathira Sujathan; Sudevan, Sachithra Thazhathuveedu; Kumar, Sunil; Mathew, Bijo

doi:10.1111/cbdd.13919

Cited by 37 publications

(24 citation statements)

References 71 publications

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“…The coumarin scaffold shows wide industrial applications and medicinal uses, of which a notable example is warfarin, the most common anticoagulant prescribed worldwide [135]. Coumarins (Figure 9 and Table 4) have been proposed as privilege scaffold and focused on as MAO inhibitors [136,137].…”

Section: Mao Inhibitory Activity Of Coumarinsmentioning

confidence: 99%

Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

et al. 2022

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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.

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Section: Mao Inhibitory Activity Of Coumarinsmentioning

confidence: 99%

Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

et al. 2022

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“…The newest marketed FDA-approved drug safinamide and lazabemide (nonmarketed) ( Figure 2 ) are reversible selective MAO-B inhibitors. 40 , 41 Moreover, the isatin small molecule is identified as a reversible MAO enzyme. The PDB IDs 1OJA and 2XFP are two protein 3D structures in MAO-B with the isatin complex.…”

Section: Introductionmentioning

confidence: 99%

Exploration of the Detailed Structure–Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

2022

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Monoamine oxidase (MAO) is a protein with a key function in the catabolism of neuroamines in both central and peripheral parts of the body. MAO-A and -B are two isozymes of this enzyme which have emerged to be considered as a drug target for the treatment of neurodenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Isatin is an endogenous small fragment, reversible inhibitor for MAO enzymes and is more selective for MAO-B than -A. Isatin is responsible for increasing the dopamine level in the brain by the inhibition of an MAO enzyme. The very few selective and reversible inhibitors existing for MAO proteins and the intensity of neurological diseases in humanity have opened a new door for researchers. Isatin has a polypharmacological profile in medicinal chemistry, is a reversible inhibitor for both the MAOs, and shows high selectivity potent inhibition for MAO-B. In this review, we discuss isatins and their analogues phthalide and phthalimide with structure–activity relationships (SARs), and this comprehensive information accelerates the ideas for design and development of a new class of MAO inhibitors for neurodegenerative diseases.

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“…Conjugation of coumarins with a second pharmacophore is currently gaining attention to access multitarget drugs 30 . Many of such activities are the result of the inhibition of key enzymes by coumarin-containing derivatives 20 , 31–38 , either natural or synthetic; this is due to their peculiar planar structure and to the possibility of establishing strong non-covalent interactions involving the lactone moiety (hydrogen bonding, dipole-dipole) and the aromatic scaffold (π-π and cation-π interactions) 21 . Regarding CAs, the slow inhibition mode observed for coumarins compared to sulfonamido-derivatives suggested that they might behave as suicide inhibitors 39 .…”

Section: Introductionmentioning

confidence: 99%

2-Aminobenzoxazole-appended coumarins as potent and selective inhibitors of tumour-associated carbonic anhydrases

Fuentes-Aguilar

Merino-Montiel

Montiel‐Smith

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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We have carried out the design, synthesis, and evaluation of a small library of 2-aminobenzoxazole-appended coumarins as novel inhibitors of tumour-related CAs IX and XII. Substituents on C-3 and/or C-4 positions of the coumarin scaffold, and on the benzoxazole moiety, together with the length of the linker connecting both units were modified to obtain useful structure-activity relationships. CA inhibition studies revealed a good selectivity towards tumour-associated CAs IX and XII ( K i within the mid-nanomolar range in most of the cases) in comparison with CAs I, II, IV, and VII ( K i > 10 µM); CA IX was found to be slightly more sensitive towards structural changes. Docking calculations suggested that the coumarin scaffold might act as a prodrug, binding to the CAs in its hydrolysed form, which is in turn obtained due to the esterase activity of CAs. An increase of the tether length and of the substituents steric hindrance was found to be detrimental to in vitro antiproliferative activities. Incorporation of a chlorine atom on C-3 of the coumarin moiety achieved the strongest antiproliferative agent, with activities within the low micromolar range for the panel of tumour cell lines tested.

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Deciphering the detailed structure–activity relationship of coumarins as Monoamine oxidase enzyme inhibitors—An updated review

Cited by 37 publications

References 71 publications

Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

Exploration of the Detailed Structure–Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

2-Aminobenzoxazole-appended coumarins as potent and selective inhibitors of tumour-associated carbonic anhydrases

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