Role of 13-(di)phenylalkyl berberine derivatives in the modulation of the activity of human topoisomerase IB.

PubMed ID: 25783020

Vieira S, Castelli S, Falconi M, Takarada J, Fiorillo G, Buzzetti F, Lombardi P, Desideri A

Int J Biol Macromol. 2015

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.

doi: 10.1016/j.ijbiomac.2015.02.051S0141-8130(15)00155-5

European Union