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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Published in:Biomedicines 2023-02, Vol.11 (2), p.605
Main Authors: Milusheva, Miglena, Gledacheva, Vera, Stefanova, Iliyana, Pencheva, Mina, Mihaylova, Rositsa, Tumbarski, Yulian, Nedialkov, Paraskev, Cherneva, Emiliya, Todorova, Mina, Nikolova, Stoyanka
Format: Article
Language:English
Subjects:
Anticholinergics
antispasmodics
bioelectrical activity
Biofilms
Biological activity
Calcium influx
Cell lines
Chloride channels
Chromatography
Cytotoxicity
Dosage and administration
Drug therapy
Gas flow
IBS
in silico
Irritable bowel syndrome
Leukemia
mebeverine precursor
Parasympatholytic agents
Patient outcomes
Pharmacodynamics
Physiology
Potassium
Quality of life
Smooth muscle
Solvents
synthesis
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Summary: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. 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. All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine showed a significant change in BEA due to Ca channel regulation, Ca 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 as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine as a potential effective choice for orally active long-term therapy of IBS.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines11020605