Topoisomerases IB are anticancer and antimicrobial targets whose inhibition by several natural and non-natural compounds has been documented. The inhibition effect by berberine and some 13-(di)phenylalkyl berberine derivatives has been tested towards human topoisomerase IB. Derivatives belonging to the 13-diphenylalkyl series display an efficient inhibition of the DNA relaxation and cleavage step, that increases upon pre-incubation with the enzyme. The religation step of the enzyme catalytic cycle is not affected by compounds and only slightly upon pre-incubation. The binding of the protein to the DNA substrate occurs also in the presence of the compounds, as monitored by a DNA shift assay, indicating that the compounds are not able to inhibit the formation of the enzyme-DNA complex but that they act as catalytic inhibitors.
Vieira, S., Castelli, S., Falconi, M., Takarada, J., Fiorillo, G., Buzzetti, F., et al. (2015). Role of 13-(di)phenylalkyl berberine derivatives in the modulation of the activity of human topoisomerase IB. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 77, 68-75 [10.1016/j.ijbiomac.2015.02.051].
Role of 13-(di)phenylalkyl berberine derivatives in the modulation of the activity of human topoisomerase IB
CASTELLI, SILVIA;FALCONI, MATTIA;DESIDERI, ALESSANDRO
2015-01-01
Abstract
Topoisomerases IB are anticancer and antimicrobial targets whose inhibition by several natural and non-natural compounds has been documented. The inhibition effect by berberine and some 13-(di)phenylalkyl berberine derivatives has been tested towards human topoisomerase IB. Derivatives belonging to the 13-diphenylalkyl series display an efficient inhibition of the DNA relaxation and cleavage step, that increases upon pre-incubation with the enzyme. The religation step of the enzyme catalytic cycle is not affected by compounds and only slightly upon pre-incubation. The binding of the protein to the DNA substrate occurs also in the presence of the compounds, as monitored by a DNA shift assay, indicating that the compounds are not able to inhibit the formation of the enzyme-DNA complex but that they act as catalytic inhibitors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.