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- Title
4-Isobutylmethcathinone—A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers.
- Authors
Paškan, Martin; Rimpelová, Silvie; Svobodová Pavlíčková, Vladimíra; Spálovská, Dita; Setnička, Vladimír; Kuchař, Martin; Kohout, Michal
- Abstract
New psychoactive substances and among them synthetic cathinones represent a significant threat to human health globally. However, within such a large pool of substances derived from a natural compound ((S)-cathinone), substances with important pharmaceutical uses can be identified, as already documented by bupropione. Therefore, this work aimed to find a synthetic pathway for a novel synthetic cathinone, namely 4-isobutylmethcathinone, and describe its spectroscopic properties and biological activity in vitro. Since cathinones comprise a chiral center in their structure, a method for chiral separation of the substance was elaborated using high-performance liquid chromatography on an analytical and preparative scale. Preparative enantioseparation on a polysaccharide column provided a sufficient amount of the drug for the chiroptical studies leading to the determination of the absolute configuration of enantiomers as well as for their subsequent in vitro cytotoxicity study. The cytotoxicity induced by 4-isobutylmethcathinone was determined in human cells derived from the urinary bladder (5637), neuroblastoma (SH-SY5Y), microglia (HMC-3), and hepatocellular carcinoma (Hep G2), in which the IC50 values after 72 h reached an 18–65 µM concentration. This is significantly higher cytotoxicity in comparison with other synthetic cathinones. In the receptor binding studies, a significant difference in the agonistic effect on dopamine and adrenergic receptors of individual enantiomers was observed. The lack of binding affinity towards the serotonin receptors then relates 4-isobutylmethcathinone to the family of monoamine drugs, such as 3,4-methylenedioxymathamphetamine (ecstasy, MDMA).
- Subjects
ENANTIOMERS; CATHINONE; SEROTONIN receptors; HIGH performance liquid chromatography; ADRENERGIC receptors; DOPAMINE receptors; SYNTHETIC cathinone
- Publication
Pharmaceuticals (14248247), 2022, Vol 15, Issue 12, p1495
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph15121495