In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors
Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological...
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/605 |
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| author | Miglena Milusheva Vera Gledacheva Iliyana Stefanova Mina Pencheva Rositsa Mihaylova Yulian Tumbarski Paraskev Nedialkov Emiliya Cherneva Mina Todorova Stoyanka Nikolova |
| author_facet | Miglena Milusheva Vera Gledacheva Iliyana Stefanova Mina Pencheva Rositsa Mihaylova Yulian Tumbarski Paraskev Nedialkov Emiliya Cherneva Mina Todorova Stoyanka Nikolova |
| author_sort | Miglena Milusheva |
| collection | DOAJ |
| description | Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. Methods: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. Results: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine <b>3</b> showed a significant change in BEA due to Ca<sup>2+</sup> channel regulation, Ca<sup>2+</sup> influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine <b>3</b> as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. Conclusion: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine <b>3</b> as a potential effective choice for orally active long-term therapy of IBS. |
| first_indexed | 2024-03-11T09:05:49Z |
| format | Article |
| id | doaj.art-43e25f5ebc7e4c5887e72a9feea27636 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:05:49Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-43e25f5ebc7e4c5887e72a9feea276362023-11-16T19:20:43ZengMDPI AGBiomedicines2227-90592023-02-0111260510.3390/biomedicines11020605In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine PrecursorsMiglena Milusheva0Vera Gledacheva1Iliyana Stefanova2Mina Pencheva3Rositsa Mihaylova4Yulian Tumbarski5Paraskev Nedialkov6Emiliya Cherneva7Mina Todorova8Stoyanka Nikolova9Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, BulgariaDepartment of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, BulgariaDepartment of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, BulgariaDepartment of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, BulgariaLaboratory of Experimental Chemotherapy, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University, 1431 Sofia, BulgariaDepartment of Microbiology, Technological Faculty, University of Food Technologies, 4002 Plovdiv, BulgariaDepartment of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaDepartment of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Organic Chemistry, Faculty of Chemistry, University of Plovdiv, 4000 Plovdiv, BulgariaDepartment of Organic Chemistry, Faculty of Chemistry, University of Plovdiv, 4000 Plovdiv, BulgariaIrritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. Methods: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. Results: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine <b>3</b> showed a significant change in BEA due to Ca<sup>2+</sup> channel regulation, Ca<sup>2+</sup> influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine <b>3</b> as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. Conclusion: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine <b>3</b> as a potential effective choice for orally active long-term therapy of IBS.https://www.mdpi.com/2227-9059/11/2/605synthesismebeverine precursorIBSin silicobioelectrical activityantispasmodics |
| spellingShingle | Miglena Milusheva Vera Gledacheva Iliyana Stefanova Mina Pencheva Rositsa Mihaylova Yulian Tumbarski Paraskev Nedialkov Emiliya Cherneva Mina Todorova Stoyanka Nikolova In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors Biomedicines synthesis mebeverine precursor IBS in silico bioelectrical activity antispasmodics |
| title | In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors |
| title_full | In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors |
| title_fullStr | In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors |
| title_full_unstemmed | In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors |
| title_short | In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors |
| title_sort | in silico in vitro and ex vivo biological activity of some novel mebeverine precursors |
| topic | synthesis mebeverine precursor IBS in silico bioelectrical activity antispasmodics |
| url | https://www.mdpi.com/2227-9059/11/2/605 |
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