Computational insights into β-carboline inhibition of monoamine oxidase A

Alja Prah (Author), Tanja Gavranić (Author), Andrej Perdih (Author), Marija Sollner Dolenc (Author), Janez Mavri (Author)

Abstract

Monoamine oxidases (MAOs) are an important group of enzymes involved in the degradation of neurotransmitters and their imbalanced mode of action may lead to the development of various neuropsychiatric or neurodegenerative disorders. In this work, we report the results of an in-depth computational study in which we performed a static and a dynamic analysis of a series of substituted β-carboline natural products, found mainly in roasted coffee and tobacco smoke, that bind to the active site of the MAO‑A isoform. By applying molecular docking in conjunction with structure-based pharmacophores and molecular dynamics simulations coupled with dynamic pharmacophores, we extensively investigated the geometric aspects of MAO-A binding. To gain insight into the energetics of binding, we used the linear interaction energy (LIE) method and determined the key anchors that allow productive β-carboline binding to MAO-A. The results presented herein could be applied in the rational structure-based design and optimization of β-carbolines towards preclinical candidates that would target the MAO-A enzyme and would be applicable especially in the treatment of mental disorders such as depression.

Keywords

monoaminooksidaza;β-karbolini;energija linearne interakcije;monoamine oxidase;β-carbolines;depression;linear interaction energy;

Data

Language:	English
Year of publishing:	2022
Typology:	1.01 - Original Scientific Article
Organization:	UL FFA - Faculty of Pharmacy
UDC:	616.895.4:616-085
COBISS:	124842499
ISSN:	1420-3049
Views:	4
Downloads:	0
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	Depresija (medicina);Zdravljenje;
Type (COBISS):	Article
Pages:	20 str.
Volume:	ǂVol. ǂ27
Issue:	ǂiss. ǂ19, ǂart. ǂ6711
Chronology:	2022
DOI:	10.3390/molecules27196711
ID:	16706492