Antimicrobial and cytotoxic effects of ammonium derivatives of diterpenoids steviol and isosteviol

Antimicrobial and cytotoxic effects of ammonium derivatives of
diterpenoids steviol and isosteviol
Alexandra D. Voloshina *, Anastasiia S. Sapunova, Natalia V. Kulik, Mayya G. Belenok,
Irina Yu Strobykina, Anna P. Lyubina, Syumbelya K. Gumerova, Vladimir E. Kataev
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov str., 8, Kazan 420088, Russia
A R T I C L E I N F O
Keywords:
Steviol
Isosteviol
Ammonium compounds
Antimicrobial activity
Antibacterial activity
Cytotoxicity
Hemolysis
Drug resistance
Apoptosis
Mitochondria
A B S T R A C T
Antimicrobial and cytotoxic activities of several ammonium derivatives of diterpenoids steviol and isosteviol
have been investigated in vitro. The results have showed that these compounds possess high antibacterial activity
against MRSA strains and cytotoxic effect against cancer cell lines MCF-7, M􀀀 HeLa, A-549, PC3, HepG2, T98G.
Lead compounds 4 and 5 were detected, which, in the case of the MCF-7 cell line (human breast adenocarcinoma),
showed IC50 at the doxorubicin level with a selectivity index of 5.0–5.2. Flow cytometry and laser
confocal microscopy analysis demonstrated that the mechanism of cytotoxic effects of the tested compounds on
MCF-7 cells could be associated with the induction of apoptosis along the mitochondrial pathway. At the same
time, they did not cause hemolysis and showed only slight cytotoxicity with respect to normal human cells of
embryonic lung (Wi-38).
The obtained results allow us to consider the studied compounds as promising scaffolds for the design of new
effective antibacterial drugs and anticancer agents targeting mitochondria.