This work was funded by FCT and FEDER through CQ-UM and CFUM, project POCI/QUI/59407/2004 and post-Doc grant (SFRH/BPD/24548/2005) of A.S.A

Abreu, Ana S.

Carvalho, M. Solange D.

Castanheira, Elisabete M. S.

Ferreira, Paula M. T.

Queiroz, Maria João R. P.

Universidade do Minho: RepositoriUM

Interaction of a potential antitumoral benzothieno[3,2-b]pyrrole with lipid membranes and salmon sperm DNA  Ana S. Abreu,a,b M. Solange D. Carvalho,a Elisabete M.S. Castanheira,b  Maria-João R.P. Queiroz,a Paula M.T. Ferreira a   a) Centre of Chemistry, b) Centre of Physics, Univ. of Minho, Campus de Gualtar,  4710-057 Braga, Portugal. e-mail: anabreu@quimica.uminho.pt    In this work, the interaction of a potential antitumoral benzothieno[3,2-b]pyrrole (BTP) with lipid membranes and natural salmon sperm DNA was studied by fluorescence techniques. Studies of the influence of BTP on the growth of human tumor cell lines showed that this compound highly inhibit the growth of NCI-H460 (non-small cell lung cancer) cells with a GI50 = 3.9 µM. The interaction of the fluorescent BTP with ds-DNA allowed the determination of a binding constant of Ki = (2.9 ± 0.3)×106 M-1 and a binding site size of n = 2.0 ± 0.7, pointing to a high affinity of this compound to the macromolecule. Fluorescence quenching experiments using I- point to an intercalative mode of binding. Fluorescence studies of BTP incorporated in lipid aggregates of DPPC, DOPE and Egg-PC (Fig. 1) indicate that this compound is located mainly near the hydrophobic lipid tails and is able to distinguish between the rigid gel phase and fluid phases.                   Fig. 1 - Fluorescence spectra of BTP in lipid membranes of DOPE, Egg-PC and DPPC. Inset: Fluorescence spectra of BTP in cyclohexane and ethanol at 55 ºC.     Acknowledgements: This work was funded by FCT and FEDER through CQ-UM and CFUM, project POCI/QUI/59407/2004 and post-Doc grant (SFRH/BPD/24548/2005) of A.S.A. N CO2MeSHSBTP

Interaction of a potential antitumoral benzothieno[3,2-b]pyrrole with lipid membranes and salmon sperm DNA

http://repositorium.sdum.uminho.pt/bitstream/1822/13799/1/Abstract%20BTP_Sofia%20Biophysics2008.pdf

Interaction of a potential antitumoral benzothieno[3,2-b]pyrrole with lipid membranes and salmon sperm DNA

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