New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and encapsulation in nanoliposomes

This work was funded by FCT-Portugal and FEDER through CFUM, CQ-UM, Project PTDC/QUI/81238/2006 cofinanced by FCT and program FEDER/COMPETE (FCOMP-01-0124-FEDER-007467) and PhD grants of M.S.D. Carvalho (SFRH/BD/47052/2008) and R.C. Calhelha (SFRH/BD/29274/2006)

Fluorescence studies of potential antitumoral 6-heteroarylthieno[3,2-b]pyridines in solution and in nanoliposomes

Fluorescence properties of new potential antitumoral 6-heteroarylthieno[3,2-b]pyridines, recently synthesized, were studied in solution and in nanoliposomes of different compositions. The results indicate that these compounds can be transported in the hydrophobic region of the lipid bilayer. The liposomal formulation Egg-PC:Ch:DPPG (7:3:1) is the one with smaller size and lowest polydispersity.CFUM - PEst-C/FIS/UI0607/2011 (F-COMP-01-0124-FEDER-022711)Fundação para a Ciência e a Tecnologia - SFRH/BD/47052/2008)CQ/UM - PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716), PTDC/QUI/81238/2006 (FCOMP-01-0124-FEDER-007467)FEDE

Fluorescence studies on new potential antitumoral benzothienopyran-1-ones in solution and in lipid membranes

This work was funded by Foundation for Science and Technology (FCT, Portugal) and FEDER through CFUM and CQ-UM, research project PTDC/QUI/81238/2006 and PhD grants of M.S.D. Carvalho SFRH/BD/47052/2008 and of R.C. Calhelha SFRH/BD/29274/2006

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

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

Fluorescence studies on potential antitumoral heteroaryl and heteroannulated indoles in solution and in lipid membranes

Fluorescence properties of three potential antitumoral 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 phosphatidylethanolamine (DOPE) and egg yolk phosphatidylcholine (Egg-PC). The 3-(dibenzofur-4-yl)indole 3 exhibits the higher fluorescence quantum yields in all solvents studied (0.32 ≤ ΦF ≤ 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. Fluorescence (steady-state) anisotropy measurements of the compounds 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.Fundação para a Ciência e a Tecnologia (FCT) - Projecto POCI/QUI/59407/2004, bolsa doutoramento SFRH/BPD/24548/2005Fundo Europeu de Desenvolvimento Regional (FEDER

Fluorescence studies of new potential antitumoral indole derivatives in lipid membranes

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

New tetracyclic heteroaromatic compounds based on dehydroamino acids : photophysical and electrochemical studies of interaction with DNA

A benzothienoindole (BTIN) and a benzofuroindole (BFIN) were synthesized in high yields, as potential new target DNA compounds, using a metal-assisted intramolecular C-N cyclization, developed by us, of the methyl esters of N-(t-butoxycarbonyl)-b,b-bis(dibenzothien-4-yl or dibenzofuro-4-yl)dehydroalanines. The latter were obtained by a bis-Suzuki coupling of a b,b-dibromodehydroalanine with the corresponding heteroarylboronic acids. The absorption and fluorescence properties of the novel tetracyclic heteroaromatic compounds were studied in different solvents and in the presence of natural double-stranded (ds) salmon sperm DNA. The results in several solvents show that either BTIN or BFIN can be used as fluorescence solvent sensitive probes. Spectroscopic studies of the interaction of both compounds with dsDNA allowed to determine binding constant (Ki) values and binding site sizes (n). Fluorescence quenching experiments using iodide ion allowed the determination of the accessibilities to the quencher, showing that intercalation is the preferred mode of binding of these molecules to DNA. From the results obtained BTIN is the more intercalative compound and has a higher affinity to DNA. The interaction of this more promising compound with DNA was also studied electrochemically, by using differential pulse voltammetry (DPV) in connection with disposable pencil graphite electrode (PGE). These studies are based on the differences in the BTIN and adenine oxidation signals. After the interaction of BTIN with DNA, the oxidation signals of BTIN and adenine strongly decreased. The latter was attributed to the binding of the BTIN to DNA and the former points to a possible damage of the oxidizable groups of the compound after intercalation into DNA. Several concentrations of BTIN were tested and 50 μg/mL was found to be the optimum concentration in order to detect its interaction with DNA. In addition, the detection limit and the reproducibility were determined by using a disposable electrochemical transducer. The results of spectroscopic and electrochemical detection of BTIN interaction with DNA are in good agreement.Academy of Pharmacists and Turkish Pharmacists Association (TEB)Turkish Academy of Sciences - Young Scientist Award Program (KAE/TUBA-GEBIP/2001-2-8)FEDERFundação para a Ciência e a Tecnologia (FCT) - Projecto POCI/QUI/59407/2004. A.S.A. acknowledges a post-doc. grant SFRH/BPD/24548/2005, Bolsa SFRH/BPD/24548/2005.Scientific and Technical Research Council of Turkey (TUBITAK)

Synthesis of fluorescent heteroaromatic compounds using dehydroamino acids as building blocks, studies of DNA and biomembranes interactions : evaluation of antiproliferative effects on tumor cell lines

Thanks are due to the Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER to financial support through the research centres, the research project POCI/59407/2004 and pos-Doc grants attributed to A.S.Abreu (SFRH/BPD/24548/2005) and to L.V.-S. (SFRH/BPD/29112/2006)

Benzothienoquinolines: new one-pot synthesis and fluorescence studies of their interaction with DNA and polynucleotides

Revised version. "Available online 10 August 2014"In this work, we were able to obtain the benzothieno[3,2-b]quinoline 1 and benzothieno[2,3-c]quinoline 2 using a new one-pot procedure from the reaction of the commercially available 3-bromobenzo[b]thiophene-2-carbaldehyde with 2-aminophenylpinacolborane under Suzuki coupling conditions using a stereochemically hindered ligand, 2-(cyclohexylphosphane)biphenyl and Ba(OH)2.8H2O as the base. Fluorescence properties of the benzothieno[3,2-b]quinoline 1 and the benzothieno[2,3-c]quinoline 2 were studied in solvents of different polarity. Both compounds exhibit a solvent sensitive emission, compound 1 being less fluorescent (quantum yield < 0.05) than compound 2 (quantum yield between 0.04 and 0.10). The interaction of these compounds with salmon sperm DNA and synthetic double-stranded heteropolynucleotides, poly(dA–dT)•(dA–dT) and poly(dG–dC)•(dG–dC), was studied using spectroscopic methods, allowing the determination of the intrinsic binding constants and binding site sizes. The interaction of both compounds is stronger with adenine-thymine (A-T) base pairs. Compound 1 is the most intercalative in salmon sperm DNA (47%) and polynucleotides (46%-49% of intercalated molecules), while for compound 2, 41% is intercalated in salmon sperm DNA and only 8% in poly(dG–dC)•(dG–dC). Docking studies indicate that compound 1 interacts more strongly with DNA than compound 2, with a significant value of binding free energy in the case of intercalation. Minor groove binding is also very favorable and, probably, both mechanisms occur with a preponderance of intercalation in the case of compound 1. Overall, these results indicate that both benzothienoquinolines interact with nucleic acids by both intercalation and groove binding.Foundation for the Science and Technology (FCT, Portugal), for financial support to the Portuguese NMR network (PTNMR) and also to FEDER and QREN for financial support to the Research Centres, CFUM [Strategic Project PEst-C/FIS/UI0607/2013 (FCOMP-01-0124-FEDER-037291)] and CQ/UM [Strategic Project PEst-C/QUI/UI0686/2013 (FCOMP-01-0124-FEDER-037302)], and to the research project PTDC/QUI-QUI/111060/2009 (F-COMP-01-0124-FEDER-015603) also financed by COMPETE/QREN/EU. FCT, POPH-QREN and FSE are acknowledged for the PhD grants of A.R.O.R. (SFRH/BD/90949/2012) and M.S.D.C. (SFRH/BD/47052/2008), for the Post-Doc. Grant of R.C.C. (SFRH/BPD/68344/2010) and for support to MAP-Fis Doctoral Program

New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes

Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, Ki = (8.7 ± 0.9) × 103 M-1 for compound 1 and Ki = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment