ORIGINAL PAPER Fluorescence Studies on Potential Antitumoral Heteroaryl and Heteroannulated Indoles in Solution and in Lipid Membranes Elisabete M. S. Castanheira & Ana S. Abreu & M. Solange D. Carvalho & Maria-João R. P. Queiroz & Paula M. T. Ferreira Received: 7 August 2008 / Accepted: 3 November 2008 / Published online: 29 November 2008 # Springer Science + Business Media, LLC 2008 Abstract Fluorescence properties of three potential anti- tumoral compounds, a 3-(dibenzothien-4-yl)indole 1,a phenylbenzothienoindole 2 and a 3-(dibenzofur-4-yl)indole 3, were studied in solution and in lipid aggregates of dipalmitoyl phosphatidylcholine (DPPC), dioleoyl phos- phatidylethanolamine (DOPE) and egg yolk phosphatidyl- choline (Egg-PC). The 3-(dibenzofur-4-yl)indole 3 exhibits the higher fluorescence quantum yields in all solvents studied (0.32 ≤ Φ F ≤ 0.51). All the compounds present a solvent sensitive emission, with significant red shifts in alcohols. The results point to an ICT character of the excited state, more pronounced for compound 1. Fluores- cence (steady-state) anisotropy measurements of the com- pounds incorporated in lipid aggregates of DPPC, DOPE and Egg-PC indicate that the three compounds are deeply located in the lipid bilayer, feeling the difference between the rigid gel phase and fluid phases. Keywords Heteroaryl and heteroannulated indoles . Lipid membranes . Fluorescence anisotropy Abbreviations DPPC dipalmitoyl phosphatidylcholine DOPE dioleoyl phosphatidylethanolamine Egg-PC egg yolk phosphatidylcholine PC phosphatidylcholine PE phosphatidylethanolamine Introduction For some years now our research group has synthesized a large variety of new fluorescent planar heteroaromatic compounds from dehydroamino acid derivatives, using metal-mediated reactions [1–3] and some of them were shown to be DNA intercalators [3]. Studies of incorporation in lipid vesicles using fluores- cence techniques were also performed with biological active tetracyclic planar compounds derivatives of benzo[b]thio- phenes and pyridines, a benzothienopyridopyrimidone [4] and a thieno-δ-carboline [5], prepared by us. These studies are very useful for controlled drug release assays. More recently, some of us have described the synthesis of new heteroaryl and heteroannulated indoles from dehydro- phenylalanines, a methyl 3-(dibenzothien-4-yl)indole-2- carboxylate 1, a methyl 1-phenyl-3H-benzothieno[2,3-e] indole-2-carboxylate 2, a methyl 3-(dibenzofur-4-yl)indole- 2-carboxylate 3 and a methyl 1-phenyl-3H-benzofuro[2,3-e] indole-2-carboxylate. Compounds 1-3 (Fig. 1) were evaluat- ed for their capacity to inhibit the in vitro growth of three human tumor cell lines, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer). The indolic compounds 1 and 3 gave the best anti- proliferative results but compound 1 was shown to be the most potent with GI 50 (50% of cell growth inhibition) values ranging from 11–17μM in all cell lines studied [6]. These results suggested us to perform fluorescence studies of incorporation of compounds 1–3 in lipid J Fluoresc (2009) 19:501–509 DOI 10.1007/s10895-008-0439-6 E. M. S. Castanheira (*) : A. S. Abreu Centro de Física, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal e-mail: ecoutinho@fisica.uminho.pt A. S. Abreu : M. S. D. Carvalho : M.-J. R. P. Queiroz : P. M. T. Ferreira Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal