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Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds

Three groups of synthetic lipids are chosen for studies: (1) 1,4-dihydropyridines (1,4-DHPs) containing two cationic moieties and their analogues; (2) 3,4-dihydro-2(1H)-pyridones containing a cationic moiety; and (3) acyclic, open-chain analogues, i.e., 2-amino-3-alkoxycarbonylalkylammonium derivati...

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Autores principales: Rucins, Martins, Smits, Rufus, Sipola, Anda, Vigante, Brigita, Domracheva, Ilona, Turovska, Baiba, Muhamadejev, Ruslan, Pajuste, Karlis, Plotniece, Mara, Sobolev, Arkadij, Duburs, Gunars, Plotniece, Aiva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790557/
https://www.ncbi.nlm.nih.gov/pubmed/33488932
http://dx.doi.org/10.1155/2020/8413713
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author Rucins, Martins
Smits, Rufus
Sipola, Anda
Vigante, Brigita
Domracheva, Ilona
Turovska, Baiba
Muhamadejev, Ruslan
Pajuste, Karlis
Plotniece, Mara
Sobolev, Arkadij
Duburs, Gunars
Plotniece, Aiva
author_facet Rucins, Martins
Smits, Rufus
Sipola, Anda
Vigante, Brigita
Domracheva, Ilona
Turovska, Baiba
Muhamadejev, Ruslan
Pajuste, Karlis
Plotniece, Mara
Sobolev, Arkadij
Duburs, Gunars
Plotniece, Aiva
author_sort Rucins, Martins
collection PubMed
description Three groups of synthetic lipids are chosen for studies: (1) 1,4-dihydropyridines (1,4-DHPs) containing two cationic moieties and their analogues; (2) 3,4-dihydro-2(1H)-pyridones containing a cationic moiety; and (3) acyclic, open-chain analogues, i.e., 2-amino-3-alkoxycarbonylalkylammonium derivatives. 1,4-DHPs possessing dodecyl alkyl chains in the ester groups in positions 3 and 5 and cationic nitrogen-containing groups in positions 2 and 6 have high cytotoxicity in cancer cells HT-1080 (human lung fibrosarcoma) and MH-22A (mouse hepatoma), but low cytotoxicity in the noncancerous NIH3T3 cells (mouse embryonic fibroblast). On the contrary, similar compounds having short (methyl, ethyl, or propoxyethyl) chains in the ester groups in positions 3 and 5 lack cytotoxicity in the cancer cells HT-1080 and MH-22A even at high doses. Inclusion of fluorine atoms in the alkyl chains in positions 3 and 5 of the DHP cycle decreases the cytotoxicity of the mentioned compounds. Structurally related dihydropyridones with a polar head group are substantially more toxic to normal and cancerous cells than the DHP analogues. Open-chain analogues of DHP lipids comprise the same conjugated aminovinylcarbonyl moiety and possess anticancer activity, but they also have high basal cytotoxicity. Electrochemical oxidation data demonstrate that oxidation potentials of selected compounds are in the range of 1.6–1.7 V for cationic 1,4-DHP, 2.0–2.4 V for cationic 3,4-dihydropyridones, and 1.2–1.5 V for 2-amino-3-alkoxycarbonylalkylammonium derivatives. Furthermore, the tested cationic 1,4-DHP amphiphiles possess antiradical activity. Molecular topological polar surface area values for the tested compounds were defined in accordance with the main fragments of compound structures. The determined logP values were highest for dodecyl ester groups in positions 3 and 5 of the 1,4-DHP and lowest for short alkyl chain-containing amphiphiles.
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spelling pubmed-77905572021-01-21 Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds Rucins, Martins Smits, Rufus Sipola, Anda Vigante, Brigita Domracheva, Ilona Turovska, Baiba Muhamadejev, Ruslan Pajuste, Karlis Plotniece, Mara Sobolev, Arkadij Duburs, Gunars Plotniece, Aiva Oxid Med Cell Longev Research Article Three groups of synthetic lipids are chosen for studies: (1) 1,4-dihydropyridines (1,4-DHPs) containing two cationic moieties and their analogues; (2) 3,4-dihydro-2(1H)-pyridones containing a cationic moiety; and (3) acyclic, open-chain analogues, i.e., 2-amino-3-alkoxycarbonylalkylammonium derivatives. 1,4-DHPs possessing dodecyl alkyl chains in the ester groups in positions 3 and 5 and cationic nitrogen-containing groups in positions 2 and 6 have high cytotoxicity in cancer cells HT-1080 (human lung fibrosarcoma) and MH-22A (mouse hepatoma), but low cytotoxicity in the noncancerous NIH3T3 cells (mouse embryonic fibroblast). On the contrary, similar compounds having short (methyl, ethyl, or propoxyethyl) chains in the ester groups in positions 3 and 5 lack cytotoxicity in the cancer cells HT-1080 and MH-22A even at high doses. Inclusion of fluorine atoms in the alkyl chains in positions 3 and 5 of the DHP cycle decreases the cytotoxicity of the mentioned compounds. Structurally related dihydropyridones with a polar head group are substantially more toxic to normal and cancerous cells than the DHP analogues. Open-chain analogues of DHP lipids comprise the same conjugated aminovinylcarbonyl moiety and possess anticancer activity, but they also have high basal cytotoxicity. Electrochemical oxidation data demonstrate that oxidation potentials of selected compounds are in the range of 1.6–1.7 V for cationic 1,4-DHP, 2.0–2.4 V for cationic 3,4-dihydropyridones, and 1.2–1.5 V for 2-amino-3-alkoxycarbonylalkylammonium derivatives. Furthermore, the tested cationic 1,4-DHP amphiphiles possess antiradical activity. Molecular topological polar surface area values for the tested compounds were defined in accordance with the main fragments of compound structures. The determined logP values were highest for dodecyl ester groups in positions 3 and 5 of the 1,4-DHP and lowest for short alkyl chain-containing amphiphiles. Hindawi 2020-12-31 /pmc/articles/PMC7790557/ /pubmed/33488932 http://dx.doi.org/10.1155/2020/8413713 Text en Copyright © 2020 Martins Rucins et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rucins, Martins
Smits, Rufus
Sipola, Anda
Vigante, Brigita
Domracheva, Ilona
Turovska, Baiba
Muhamadejev, Ruslan
Pajuste, Karlis
Plotniece, Mara
Sobolev, Arkadij
Duburs, Gunars
Plotniece, Aiva
Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds
title Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds
title_full Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds
title_fullStr Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds
title_full_unstemmed Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds
title_short Pleiotropic Properties of Amphiphilic Dihydropyridines, Dihydropyridones, and Aminovinylcarbonyl Compounds
title_sort pleiotropic properties of amphiphilic dihydropyridines, dihydropyridones, and aminovinylcarbonyl compounds
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790557/
https://www.ncbi.nlm.nih.gov/pubmed/33488932
http://dx.doi.org/10.1155/2020/8413713
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