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

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 scre...

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Autores principales: Maafi, Negar, Mamun, Abdullah Al, Janďourek, Ondřej, Maříková, Jana, Breiterová, Kateřina, Diepoltová, Adéla, Konečná, Klára, Hošťálková, Anna, Hulcová, Daniela, Kuneš, Jiří, Kohelová, Eliška, Koutová, Darja, Šafratová, Marcela, Nováková, Lucie, Cahlíková, Lucie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512562/
https://www.ncbi.nlm.nih.gov/pubmed/34641567
http://dx.doi.org/10.3390/molecules26196023
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author Maafi, Negar
Mamun, Abdullah Al
Janďourek, Ondřej
Maříková, Jana
Breiterová, Kateřina
Diepoltová, Adéla
Konečná, Klára
Hošťálková, Anna
Hulcová, Daniela
Kuneš, Jiří
Kohelová, Eliška
Koutová, Darja
Šafratová, Marcela
Nováková, Lucie
Cahlíková, Lucie
author_facet Maafi, Negar
Mamun, Abdullah Al
Janďourek, Ondřej
Maříková, Jana
Breiterová, Kateřina
Diepoltová, Adéla
Konečná, Klára
Hošťálková, Anna
Hulcová, Daniela
Kuneš, Jiří
Kohelová, Eliška
Koutová, Darja
Šafratová, Marcela
Nováková, Lucie
Cahlíková, Lucie
author_sort Maafi, Negar
collection PubMed
description 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.
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spelling pubmed-85125622021-10-14 Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents Maafi, Negar Mamun, Abdullah Al Janďourek, Ondřej Maříková, Jana Breiterová, Kateřina Diepoltová, Adéla Konečná, Klára Hošťálková, Anna Hulcová, Daniela Kuneš, Jiří Kohelová, Eliška Koutová, Darja Šafratová, Marcela Nováková, Lucie Cahlíková, Lucie Molecules Article 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. MDPI 2021-10-04 /pmc/articles/PMC8512562/ /pubmed/34641567 http://dx.doi.org/10.3390/molecules26196023 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maafi, Negar
Mamun, Abdullah Al
Janďourek, Ondřej
Maříková, Jana
Breiterová, Kateřina
Diepoltová, Adéla
Konečná, Klára
Hošťálková, Anna
Hulcová, Daniela
Kuneš, Jiří
Kohelová, Eliška
Koutová, Darja
Šafratová, Marcela
Nováková, Lucie
Cahlíková, Lucie
Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents
title Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents
title_full Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents
title_fullStr Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents
title_full_unstemmed Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents
title_short Semisynthetic Derivatives of Selected Amaryllidaceae Alkaloids as a New Class of Antimycobacterial Agents
title_sort semisynthetic derivatives of selected amaryllidaceae alkaloids as a new class of antimycobacterial agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512562/
https://www.ncbi.nlm.nih.gov/pubmed/34641567
http://dx.doi.org/10.3390/molecules26196023
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