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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/6970 |
| _version_ | 1797605178251149312 |
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| author | Beata Morak-Młodawska Małgorzata Jeleń Emilia Martula Rafał Korlacki |
| author_facet | Beata Morak-Młodawska Małgorzata Jeleń Emilia Martula Rafał Korlacki |
| author_sort | Beata Morak-Młodawska |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T04:57:26Z |
| format | Article |
| id | doaj.art-c0326a8d7df94522954f629715d704e9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:57:26Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c0326a8d7df94522954f629715d704e92023-11-17T19:33:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248697010.3390/ijms24086970Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer ActionBeata Morak-Młodawska0Małgorzata Jeleń1Emilia Martula2Rafał Korlacki3Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of SilesiaJagiellońska 4, 41-200 Sosnowiec, PolandDepartment of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of SilesiaJagiellońska 4, 41-200 Sosnowiec, PolandDoctoral School, The Medical University of Silesia, 40-055 Katowice, PolandDepartment of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USALipophilicity 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.https://www.mdpi.com/1422-0067/24/8/6970lipophilicity1,9-diazaphenothiazinesanticancer actionADMELipinski’s rule of fiveGhose’s and Veber’s rules |
| spellingShingle | Beata Morak-Młodawska Małgorzata Jeleń Emilia Martula Rafał Korlacki Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action International Journal of Molecular Sciences lipophilicity 1,9-diazaphenothiazines anticancer action ADME Lipinski’s rule of five Ghose’s and Veber’s rules |
| 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 | lipophilicity 1,9-diazaphenothiazines anticancer action ADME Lipinski’s rule of five Ghose’s and Veber’s rules |
| url | https://www.mdpi.com/1422-0067/24/8/6970 |
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