3D-QSAR and in-silico Studies of Natural Products and Related Derivatives as Monoamine Oxidase Inhibitors

Dhiman, Priyanka; Malik, Neelam; Khatkar, Anurag

doi:10.2174/1570159x15666171128143650

Cited by 32 publications

(14 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though some aliphatic MAO substrates and inhibitors have been identified (Yu et al, 1994;Yu et al, 1995;Kalgutkar et al, 2001), most studies have shown that the presence of an aromatic ring is essential for potent MAOI activity (Wouters, 1998;Kalgutkar et al, 2001;Tripathi et al, 2018;Dhiman et al, 2018). In the specific case of AMPH derivatives, docking simulations indicate that the benzene ring of these compounds binds to MAO-A mainly via interactions with p-systems of the catalytic site residues such as Y407, Y444 (both of which form part of the so called "aromatic cage"), Y69, F208, and/or F352 (Vallejos et al, 2005;Fierro et al, 2007;Vilches-Herrera et al, 2009;Fresqui et al, 2013;Vilches-Herrera et al, 2016; Figure 2).…”

Section: Aromatic Ring Substitutionmentioning

confidence: 99%

“…The availability of MAO crystal structures has allowed a quicker pace in the rational design of novel MAOIs and in the understanding of catalytic and inhibitory mechanisms. Thus, a vast number of studies in which molecular simulation approaches have been used to rationalize and/or to predict the functional interactions between the proteins and their substrates or inhibitors have been reported recently (Ferino et al, 2012;Vianello et al, 2016;Dhiman et al, 2017;Dhiman et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

2020

View full text Add to dashboard Cite

Amphetamine and its derivatives exhibit a wide range of pharmacological activities, including psychostimulant, hallucinogenic, entactogenic, anorectic, or antidepressant effects. The mechanisms of action underlying these effects are usually related to the ability of the different amphetamines to interact with diverse monoamine transporters or receptors. Moreover, many of these compounds are also potent and selective monoamine oxidase inhibitors. In the present work, we review how structural modifications on the aromatic ring, the amino group and/or the aliphatic side chain of the parent scaffold, modulate the enzyme inhibitory properties of hundreds of amphetamine derivatives. Furthermore, we discuss how monoamine oxidase inhibition might influence the pharmacology of these compounds.

show abstract

Section: Aromatic Ring Substitutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

2020

View full text Add to dashboard Cite

show abstract

“…Macromolecular NPs are substantially more restricted in terms of the types of descriptors that can be used effectively. Generally, 3-D conformational descriptors and binding data function best for these NPs, and yield good results (Mladenović et al, 2017; Dhiman et al, 2018). QSAR has performed adequately for predicting binding affinity of antibodies to proteins—Mandrika et al describe a model consisting of 26 physicochemical descriptors (covering hydrophobicity, polarity, electronegativity, etc.)…”

Section: Cheminformatics Methodsmentioning

confidence: 99%

Informatics and Computational Methods in Natural Product Drug Discovery: A Review and Perspectives

Romano

Tatonetti

2019

Front. Genet.

View full text Add to dashboard Cite

The discovery of new pharmaceutical drugs is one of the preeminent tasks—scientifically, economically, and socially—in biomedical research. Advances in informatics and computational biology have increased productivity at many stages of the drug discovery pipeline. Nevertheless, drug discovery has slowed, largely due to the reliance on small molecules as the primary source of novel hypotheses. Natural products (such as plant metabolites, animal toxins, and immunological components) comprise a vast and diverse source of bioactive compounds, some of which are supported by thousands of years of traditional medicine, and are largely disjoint from the set of small molecules used commonly for discovery. However, natural products possess unique characteristics that distinguish them from traditional small molecule drug candidates, requiring new methods and approaches for assessing their therapeutic potential. In this review, we investigate a number of state-of-the-art techniques in bioinformatics, cheminformatics, and knowledge engineering for data-driven drug discovery from natural products. We focus on methods that aim to bridge the gap between traditional small-molecule drug candidates and different classes of natural products. We also explore the current informatics knowledge gaps and other barriers that need to be overcome to fully leverage these compounds for drug discovery. Finally, we conclude with a “road map” of research priorities that seeks to realize this goal.

show abstract

“…In the comparison with the MAO-B selective inhibitors, the potencies of DMC and BDMC were lower than or comparable to those of maackiain (0.68 µM) [14] and the piloquinone (1.21 µM) [20]. Recently, several natural heterocyclic compounds, including curcumin, have been used in computational development for their MAO inhibitory profiling [21].…”

Section: Reversibility Of Dmc and Bdmcmentioning

confidence: 98%

Inhibition of monoamine oxidase A and B by demethoxycurcumin and bisdemethoxycurcumin

Baek

Choi

Nam

et al. 2018

JABC

View full text Add to dashboard Cite

Two curcumin derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), isolated from Curcuma longa were analyzed for their inhibitory activities against two isoforms of monoamine oxidase (MAO), which is involved in the catalysis of neurotransmitting monoamines. In the study, DMC and BDMC potently inhibited human MAO-B, with IC 50 values of 2.45 and 2.59 µM, respectively, and both compounds showed effective inhibitory activities against human MAO-A, with IC 50 values of 3.24 and 3.09 µM, respectively. The inhibitory activities of the two compounds were higher than those of curcumin. The removal of the methoxy or dimethoxy groups in curcumin might increase the inhibitory activities against human MAO-A and MAO-B. The inhibited activities were recovered to almost the values of the reversible references in the dialysis experiments with DMC and BDMC. DMC and BDMC showed competitive inhibition for MAO-A and MAO-B, respectively, with K i values of 0.91 and 0.80 µM, respectively. These results suggest that the two curcumin derivatives may be useful or lead compounds in the treatment of related disorders as potent reversible MAO inhibitors.

show abstract

3D-QSAR and in-silico Studies of Natural Products and Related Derivatives as Monoamine Oxidase Inhibitors

Abstract: It is clear that, by this computational drug design approach, more particular, reversible and potent compounds can be proposed as MAO inhibitors by exact changes on the fundamental framework.

Cited by 32 publications

References 92 publications

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Amphetamine Derivatives as Monoamine Oxidase Inhibitors

Informatics and Computational Methods in Natural Product Drug Discovery: A Review and Perspectives

Inhibition of monoamine oxidase A and B by demethoxycurcumin and bisdemethoxycurcumin

Contact Info

Product

Resources

About