In vitro, in silico studies of newly isolated tetrahydro-4-(7-hydroxy-10-methoxy-6, 14-dimethyl-15-m-tolylpentadec-13-enyl) pyran-2-one and isobutyryl acetate compounds from Alstonia boonei stem bark.

Alstonia boonei is a medicinal plant use for the treatment of infections. In this study, two new compounds were purified from Alstonia boonei stem bark using standard methods and their effects on mitochondrial permeability transition and antimicrobial properties in vitro and in silico were studied. Mitochondrial Permeability Transition (mPT) pore opening and antibacterial activity of these compounds were assessed. Furthermore, the structures of these compounds were docked against caspase 3, caspase 9, Bcl2-Associated X protein (Bax), Bcl-2-antagonist/killer 1 (Bak), cytochrome c , p53, B cell lymphoma 2 (Bcl-2) and bacterial Peptidoglycan Glycosyltransferases (PGT). The two new compounds isolated were: tetrahydro-4-(7-hydroxy-10-methoxy-6, 14-dimethyl-15-m-tolylpentadec-13-enyl) pyran-2-one (1) and isobutyryl acetate (2) Compound 1 which opened the mPT pore (in vitro) at the highest concentration (80 μg/mL), had significant antimicrobial effects against P. aeruginosa ATCC 19582 and Sal. Typhi while 2 had significant effects against St aureus OK2b and K. pneumoniae ATCC4352. Compound 1 preferentially bound to Bcl-2 of all the apoptotic proteins tested and it also exhibited a higher binding affinity to PGT than compound 2. The two compounds have low toxicity. These results suggested that compound 1 can cause mitochondrial dysfunction via mitochondrial-mediated apoptosis and it could also serve as an antimicrobial agent via the disruption of the bacterial glycan core. Image 1 • Two new compounds were purified from A. boonei. • These compounds have permeability potentials in mitochondrial membrane. • They have antibacterial properties in vitro and in silico. • They have good pharmacokinetic properties. [ABSTRACT FROM AUTHOR]