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Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action

Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substitute...

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Autores principales: Morak-Młodawska, Beata, Jeleń, Małgorzata, Martula, Emilia, Korlacki, Rafał
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138389/
https://www.ncbi.nlm.nih.gov/pubmed/37108135
http://dx.doi.org/10.3390/ijms24086970
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author Morak-Młodawska, Beata
Jeleń, Małgorzata
Martula, Emilia
Korlacki, Rafał
author_facet Morak-Młodawska, Beata
Jeleń, Małgorzata
Martula, Emilia
Korlacki, Rafał
author_sort Morak-Młodawska, Beata
collection PubMed
description Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substituted 1,9-diazaphenothiazines show promising if not impressive in vitro anticancer potential, which is associated with the activation of the mitochondrial apoptosis pathway connected with to induction BAX, forming a channel in MOMP and releasing cytochrome c for the activation of caspases 9 and 3. In this publication, the lipophilicity of previously obtained 1,9-diazaphenothiazines was determined theoretically using various computer programs and experimentally using reverse-phase thin-layer chromatography (RP-TLC) and a standard curve. The study presents other physicochemical, pharmacokinetic, and toxicological properties affecting the bioavailability of the test compounds. ADME analysis was determined in silico using the SwissADME server. Molecular targets studies were identified in silico using the SwissTargetPrediction server. Lipinski’s rule of five, Ghose’s, and Veber’s rules were checked for the tested compounds, confirming their bioavailability.
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spelling pubmed-101383892023-04-28 Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action Morak-Młodawska, Beata Jeleń, Małgorzata Martula, Emilia Korlacki, Rafał Int J Mol Sci Communication Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substituted 1,9-diazaphenothiazines show promising if not impressive in vitro anticancer potential, which is associated with the activation of the mitochondrial apoptosis pathway connected with to induction BAX, forming a channel in MOMP and releasing cytochrome c for the activation of caspases 9 and 3. In this publication, the lipophilicity of previously obtained 1,9-diazaphenothiazines was determined theoretically using various computer programs and experimentally using reverse-phase thin-layer chromatography (RP-TLC) and a standard curve. The study presents other physicochemical, pharmacokinetic, and toxicological properties affecting the bioavailability of the test compounds. ADME analysis was determined in silico using the SwissADME server. Molecular targets studies were identified in silico using the SwissTargetPrediction server. Lipinski’s rule of five, Ghose’s, and Veber’s rules were checked for the tested compounds, confirming their bioavailability. MDPI 2023-04-09 /pmc/articles/PMC10138389/ /pubmed/37108135 http://dx.doi.org/10.3390/ijms24086970 Text en © 2023 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 Communication
Morak-Młodawska, Beata
Jeleń, Małgorzata
Martula, Emilia
Korlacki, Rafał
Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
title Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
title_full Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
title_fullStr Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
title_full_unstemmed Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
title_short Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
title_sort study of lipophilicity and adme properties of 1,9-diazaphenothiazines with anticancer action
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138389/
https://www.ncbi.nlm.nih.gov/pubmed/37108135
http://dx.doi.org/10.3390/ijms24086970
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