Čeština
EnglishEnhancing effect of cystamine in its amides with betulinic acid as antimicrobial and antitumor agent in vitro
Bildziukevich U., Rárová L., Janovská L., Šaman D., Wimmer Z.
STEROIDS 148: 91-98, 2019
Keywords: betulinic acid, cystamine, cytotoxicity, apoptosis, antimicrobial activity
Abstract: Amides of betulinic acid with cystamine were synthesized to investigate their antimicrobial and antitumor activity, and their influence on the cell cycle and cell apoptosis. The former target amide (6) displayed cytotoxicity in CEM cell line after 72 h of treatment (IC50=3.0 ± 0.7 μM; TI=20), and induced apoptosis by caspase-3/7 activation in CEM cells. The latter target amide (9) displayed antimicrobial activity against Streptococcus mutans (MIC 3.125 μM; MBC 3.125 μM) and Bacillus cereus (MIC 25 μM; MBC 25 μM). The achieved results demonstrate enhancing of their biological activity over that of the parent compounds. However, two intermediate compounds (2 and 7) displayed either considerable cytotoxicity (2; 7.5 ± 0.8 μM; TI=10, against G361) or antimicrobial activity (7; both against Actinomyces odontolycus and Clostridium perfrigens with MIC 12.5 μM and MBC 12.5 μM). The experimental data were compared with the in silico calculated physico-chemical and ADME parameters of the target compounds, including successful intermediates.
DOI: 10.1016/j.steroids.2019.04.004
IEB authors: Uladzimir Bildziu..., Zdeněk Wimmer
STEROIDS 148: 91-98, 2019
Keywords: betulinic acid, cystamine, cytotoxicity, apoptosis, antimicrobial activity
Abstract: Amides of betulinic acid with cystamine were synthesized to investigate their antimicrobial and antitumor activity, and their influence on the cell cycle and cell apoptosis. The former target amide (6) displayed cytotoxicity in CEM cell line after 72 h of treatment (IC50=3.0 ± 0.7 μM; TI=20), and induced apoptosis by caspase-3/7 activation in CEM cells. The latter target amide (9) displayed antimicrobial activity against Streptococcus mutans (MIC 3.125 μM; MBC 3.125 μM) and Bacillus cereus (MIC 25 μM; MBC 25 μM). The achieved results demonstrate enhancing of their biological activity over that of the parent compounds. However, two intermediate compounds (2 and 7) displayed either considerable cytotoxicity (2; 7.5 ± 0.8 μM; TI=10, against G361) or antimicrobial activity (7; both against Actinomyces odontolycus and Clostridium perfrigens with MIC 12.5 μM and MBC 12.5 μM). The experimental data were compared with the in silico calculated physico-chemical and ADME parameters of the target compounds, including successful intermediates.
DOI: 10.1016/j.steroids.2019.04.004