Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives
Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory poten...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/17/3/295 |
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| author | Anamaria Apan Dorina Casoni Denisa Leonte Cristina Pop Irina Iaru Cristina Mogoșan Valentin Zaharia |
| author_facet | Anamaria Apan Dorina Casoni Denisa Leonte Cristina Pop Irina Iaru Cristina Mogoșan Valentin Zaharia |
| author_sort | Anamaria Apan |
| collection | DOAJ |
| description | Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between −1.25 and −0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry. |
| first_indexed | 2024-04-24T17:56:29Z |
| format | Article |
| id | doaj.art-c80c3d6c29334a50b1eb4099e321a519 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-04-24T17:56:29Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c80c3d6c29334a50b1eb4099e321a5192024-03-27T13:59:13ZengMDPI AGPharmaceuticals1424-82472024-02-0117329510.3390/ph17030295Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole DerivativesAnamaria Apan0Dorina Casoni1Denisa Leonte2Cristina Pop3Irina Iaru4Cristina Mogoșan5Valentin Zaharia6Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, RomaniaDepartment of Chemistry, Faculty of Chemistry and Chemical Engineering, “Babeş-Bolyai” University, 11 Arany János Street, 400028 Cluj-Napoca, RomaniaDepartment of Organic Chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, RomaniaDepartment of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, RomaniaDepartment of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, RomaniaDepartment of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, RomaniaDepartment of Organic Chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, RomaniaLipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between −1.25 and −0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry.https://www.mdpi.com/1424-8247/17/3/295lipophilicityRP-TLCADME propertiesbioactivitythiazolo[3,2-b][1,2,4]triazolesimidazo[2,1-b][1,3,4]thiadiazoles |
| spellingShingle | Anamaria Apan Dorina Casoni Denisa Leonte Cristina Pop Irina Iaru Cristina Mogoșan Valentin Zaharia Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives Pharmaceuticals lipophilicity RP-TLC ADME properties bioactivity thiazolo[3,2-b][1,2,4]triazoles imidazo[2,1-b][1,3,4]thiadiazoles |
| title | Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives |
| title_full | Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives |
| title_fullStr | Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives |
| title_full_unstemmed | Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives |
| title_short | Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives |
| title_sort | heterocycles 52 the drug likeness analysis of anti inflammatory thiazolo 3 2 b 1 2 4 triazole and imidazo 2 1 b 1 3 4 thiadiazole derivatives |
| topic | lipophilicity RP-TLC ADME properties bioactivity thiazolo[3,2-b][1,2,4]triazoles imidazo[2,1-b][1,3,4]thiadiazoles |
| url | https://www.mdpi.com/1424-8247/17/3/295 |
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