Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
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Published:2023-04-09
Issue:8
Volume:24
Page:6970
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Morak-Młodawska Beata1ORCID, Jeleń Małgorzata1ORCID, Martula Emilia2, Korlacki Rafał3ORCID
Affiliation:
1. Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of SilesiaJagiellońska 4, 41-200 Sosnowiec, Poland 2. Doctoral School, The Medical University of Silesia, 40-055 Katowice, Poland 3. Department of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Abstract
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.
Funder
The Medical University of Silesia in Katowice
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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