DNA interaction of selected tetrahydropyrimidine and its effects against CCl 4 -induced hepatotoxicity in vivo: Part II.

Autor: Milović E; Department of Sciences, Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac, Serbia., Matić SL; Department of Sciences, Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac, Serbia., Katanić Stanković JS; Department of Sciences, Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac, Serbia., Srećković N; Department of Chemistry, Faculty of Science, University of Kragujevac, Kragujevac, Serbia., Filipović I; Department of Chemistry, Faculty of Science, University of Kragujevac, Kragujevac, Serbia., Bradić J; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia., Petrović A; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia., Jakovljević V; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Department of Human Pathology, University IM Sechenov, First Moscow State Medical University, Moscow, Russia., Vazquez NB; Department of Health Sciences, Faculty of Health Sciences, University of Burgos, Burgos, Spain., Janković N; Department of Sciences, Institute for Information Technologies Kragujevac, University of Kragujevac, Kragujevac, Serbia.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Nov; Vol. 357 (11), pp. e2400409. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1002/ardp.202400409
Abstrakt: Tetrahydropyrimidine (compound A = methyl 4-[4'-(heptyloxy)-3'-methoxyphenyl]-1,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate) was chosen for in vivo studies after exhibiting noteworthy in vitro activity against the K562 and MDA-MB-231 cell lines, with IC 50 values of 9.20 ± 0.14 µM and 12.76 ± 1.93 µM, respectively. According to experimental (fluorescence titration, viscosity, and differential scanning calorimetry) results, A interacts with DNA via the minor groove. In vivo, acute oral toxicity studies in Wistar albino rats proved no noticeable symptoms of either toxicity or death during the follow-up period. Genotoxic and antigenotoxic studies at three different concentrations of A (5, 10, and 20 mg/kg of body weight) in Wistar albino rats showed that the dose of 5 mg/kg body weight did not cause DNA damage and had a remarkable DNA protective activity against CCl 4 -induced DNA damage, with a percentage reduction of 78.7%. It is also important to note that, under the investigated concentrations of A, liver damage is not observed. Considering all experimental outcomes realized under various in vivo investigations (acute oral toxicity, genotoxicity, antigenotoxicity, and biochemical tests), compound A could be a promising candidate for further clinical testing.
(© 2024 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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