Enhancing effect of cystamine in its amides with betulinic acid as antimicrobial and antitumor agent in vitro

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 mu M; 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 mu M; MBC 3.125 mu M) and Bacillus cereus (MIC 25 mu M; MBC 25 mu M). 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 mu M; TI = 10, against G361) or antimicrobial activity (7; both against Actinomyces odontolycus and Clostridium perfrigens with MIC 12.5 mu M and MBC 12.5 mu M). The experimental data were compared with the in silica calculated physico-chemical and ADME parameters of the target compounds, including successful intermediates.