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Alkaloids and Their Synthetic Derivatives as Inspiration for Medicinal Chemistry

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 10002

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Special Issue Editors

Prof. Dr. Lucie Cahlíková

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Guest Editor

Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
Interests: isolation of secondary metabolites from plants (with focus on alkaloids from Amaryllidaceae, Papaveraceae); preparation of analogues of Amaryllidaceae alkaloids; biological activity of alkaloids and their derivatives connected with potential treatment of neurodegenerative and oncological diseases
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Dr. Jakub Chlebek

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Guest Editor

Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
Interests: isolation of secondary metabolites from plants (mainly isoquinoline and indole alkaloids from different plant families) and their biological activities related to neurodegenerative and oncological diseases

Special Issue Information

Dear Colleagues,

Alkaloids constitute a structurally diverse array of natural products, and these compounds have attracted research interest due to their pharmacological activities, which include antitumor, antibacterial, antifungal, antimalarial, antiviral, analgesic, and acetylcholinesterase inhibitory activities. Alkaloids are produced by a large variety of organisms which includes bacteria, fungi, plants and animals, the main source of which are higher plants. More than 12,000 alkaloids, including more than 150 families, have been identified in plants, and around 20% of the “species of flowering plants” contain alkaloids. Medical use of alkaloid-containing plants has a long history, and thus, when the first alkaloids were isolated in the 19th century, they immediately found application in clinical practice. Many synthetic and semisynthetic drugs are structural modifications of the alkaloids, which were designed to enhance or change the primary effect of the drug and reduce unwanted side-effects.

This Special Issue is focused on both original research and review articles that cover the analysis, isolation, and structural elucidation of all structural types of alkaloids. Evaluation of the biological activities, structure–activity relationship, preparation of semisynthetic derivatives of alkaloids, and molecular mechanisms of action are welcomed.

Prof. Dr. Lucie Cahlíková
Dr. Jakub Chlebek
Guest Editors

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Keywords

ethnobotany
phytochemistry
alkaloids
analysis
isolation
structural elucidation
biological activities
drug discovery
structure–activity relationships
total synthesis

Published Papers (4 papers)

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Research

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15 pages, 2963 KiB

Open AccessArticle

Interactions of Isoquinoline Alkaloids with Transition Metals Iron and Copper

by Mst Shamima Parvin, Jakub Chlebek, Anna Hošťálková, Maria Carmen Catapano, Zuzana Lomozová, Kateřina Macáková and Přemysl Mladěnka

Molecules 2022, 27(19), 6429; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27196429 - 29 Sep 2022

Cited by 6 | Viewed by 1379

Abstract

Data on alkaloid interactions with the physiologically important transition metals, iron and copper, are mostly lacking in the literature. However, these interactions can have important consequences in the treatment of both Alzheimer’s disease and cancer. As isoquinoline alkaloids include galanthamine, an approved drug for Alzheimer’s disease, as well as some potentially useful compounds with cytostatic potential, 28 members from this category of alkaloids were selected for a complex screening of interactions with iron and copper at four pathophysiologically relevant pH and in non-buffered conditions (dimethyl sulfoxide) by spectrophotometric methods in vitro. With the exception of the salts, all the alkaloids were able to chelate ferrous and ferric ions in non-buffered conditions, but only five of them (galanthine, glaucine, corydine, corydaline and tetrahydropalmatine) evoked some significant chelation at pH 7.5 and only the first two were also active at pH 6.8. By contrast, none of the tested alkaloids chelated cuprous or cupric ions. All the alkaloids, with the exception of the protopines, significantly reduced the ferric and cupric ions, with stronger effects on the latter. These effects were mostly dependent on the number of free aromatic hydroxyls, but not other hydroxyl groups. The most potent reductant was boldine. As most of the alkaloids chelated and reduced the ferric ions, additional experimental studies are needed to elucidate the biological relevance of these results, as chelation is expected to block reactive oxygen species formation, while reduction could have the opposite effect. Full article

(This article belongs to the Special Issue Alkaloids and Their Synthetic Derivatives as Inspiration for Medicinal Chemistry)

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21 pages, 9022 KiB

Open AccessArticle

Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents

by Negar Maafi, Abdullah Al Mamun, Ondřej Janďourek, Jana Maříková, Kateřina Breiterová, Adéla Diepoltová, Klára Konečná, Anna Hošťálková, Daniela Hulcová, Jiří Kuneš, Eliška Kohelová, Darja Koutová, Marcela Šafratová, Lucie Nováková and Lucie Cahlíková

Molecules 2021, 26(19), 6023; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26196023 - 04 Oct 2021

Cited by 1 | Viewed by 1771

Abstract

The search for novel antimycobacterial drugs is a matter of urgency, since tuberculosis is still one of the top ten causes of death from a single infectious agent, killing more than 1.4 million people worldwide each year. Nine Amaryllidaceae alkaloids (AAs) of various structural types have been screened for their antimycobacterial activity. Unfortunately, all were considered inactive, and thus a pilot series of aromatic esters of galanthamine, 3-O-methylpancracine, vittatine and maritidine were synthesized to increase biological activity. The semisynthetic derivatives of AAs were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Ra and two other mycobacterial strains (M. aurum, M. smegmatis) using a modified Microplate Alamar Blue Assay. The most active compounds were also studied for their in vitro hepatotoxicity on the hepatocellular carcinoma cell line HepG2. In general, the derivatization of the original AAs was associated with a significant increase in antimycobacterial activity. Several pilot derivatives were identified as compounds with micromolar MICs against M. tuberculosis H37Ra. Two derivatives of galanthamine, 1i and 1r, were selected for further structure optimalization to increase the selectivity index. Full article

(This article belongs to the Special Issue Alkaloids and Their Synthetic Derivatives as Inspiration for Medicinal Chemistry)

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10 pages, 2094 KiB

Open AccessArticle

Structure Elucidation and Cholinesterase Inhibition Activity of Two New Minor Amaryllidaceae Alkaloids

by Jana Maříková, Abdullah Al Mamun, Latifah Al Shammari, Jan Korábečný, Tomáš Kučera, Daniela Hulcová, Jiří Kuneš, Milan Malaník, Michaela Vašková, Eliška Kohelová, Lucie Nováková, Lucie Cahlíková and Milan Pour

Molecules 2021, 26(5), 1279; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26051279 - 26 Feb 2021

Cited by 7 | Viewed by 2601

Abstract

Two new minor Amaryllidaceae alkaloids were isolated from Hippeastrum × hybridum cv. Ferrari and Narcissus pseudonarcissus cv. Carlton. The chemical structures were identified by various spectroscopic (one- and two-dimensional (1D and 2D) NMR, circular dichroism (CD), high-resolution mass spectrometry (HRMS) and by comparison with literature data of similar compounds. Both isolated alkaloids were screened for their human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE) inhibition activity. One of the new compounds, a heterodimer alkaloid of narcikachnine-type, named narciabduliine (2), showed balanced inhibition potency for both studied enzymes, with IC₅₀values of 3.29 ± 0.73 µM for hAChE and 3.44 ± 0.02 µM for hBuChE. The accommodation of 2 into the active sites of respective enzymes was predicted using molecular modeling simulation. Full article

(This article belongs to the Special Issue Alkaloids and Their Synthetic Derivatives as Inspiration for Medicinal Chemistry)

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Review

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28 pages, 8108 KiB

Open AccessReview

Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer’s Disease

by Lucie Cahlíková, Rudolf Vrabec, Filip Pidaný, Rozálie Peřinová, Negar Maafi, Abdullah Al Mamun, Aneta Ritomská, Viriyanata Wijaya and Gerald Blunden

Molecules 2021, 26(17), 5240; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175240 - 29 Aug 2021

Cited by 13 | Viewed by 3208

Abstract

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disease recognized as the most common form of dementia among elderly people. Due to the fact that the exact pathogenesis of AD still remains to be fully elucidated, the treatment is only symptomatic and available drugs are not able to modify AD progression. Considering the increase in life expectancy worldwide, AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. Due to their complex nitrogen-containing structures, alkaloids are considered to be promising candidates for use in the treatment of AD. Since the introduction of galanthamine as an antidementia drug in 2001, Amaryllidaceae alkaloids (AAs) and further isoquinoline alkaloids (IAs) have been one of the most studied groups of alkaloids. In the last few years, several compounds of new structure types have been isolated and evaluated for their biological activity connected with AD. The present review aims to comprehensively summarize recent progress on AAs and IAs since 2010 up to June 2021 as potential drugs for the treatment of AD. Full article

(This article belongs to the Special Issue Alkaloids and Their Synthetic Derivatives as Inspiration for Medicinal Chemistry)

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