Semi-synthesis of novel thebaine derivatives with low cytotoxicity and their antibacterial and antihemolytic properties

AbstractIn the present study, some new 1,2,3-triazole-tethered analogs ofN-northebaine were designed and synthesized. The anti-bacterial properties of novel thebaine derivatives were studied onStaphylococcus aureus (S. aureus) andEscherichia coli (E. coli). Based on the results, compounds5b,5j and5m showed the best activities againstS. aureus (minimum inhibitory concentration (MIC)  ~ 25 μM) compared to the parent compound (MIC ~ 321 μM). The most active anti-bacterial derivatives (i.e.,5b,5j and5m) and thebaine were considered as potent anti-bacterial wound healing agents. In this regard, fibroblast cell cytotoxicity and proliferation as well as anti-hemolytic activities of the mentioned compounds were studied. The cytotoxicity assay by using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide (MTT) on human dermal fibroblast cell lines (HDF) revealed that products5j and5m didn ’t show inhibition of cell line growth after 24 h. Based on the investigation results on blood cell disruption for releasing of hemoglobin, compound5j didn ’t exhibit any hemolysis activity in different doses.Graphical Abstract
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research