Synthesis of novel benzofurocoumarin analogues and their anti-proliferative effect on human cancer cell lines

The synthesis of five new tetracyclic benzofurocoumarin (benzopsoralen) analogues is described. Their inhibitory effects on the growth of three human tumour cell lines (MDA MB 231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma)) were evaluated, and discussed in terms of structure–activity relationship.FCT and FEDER, for National NMR Network (Bruker Avance II 400), REEQ/630/QUI/2005 (LC/MS instrument) and the PhD grant (SFRH/BD/48636/2008)

Synthesis of novel psoralen analogues and in vitro antitumor activity

Psoralens are natural products present in several plant families that are extremely toxic to a wide variety of prokaryotic and eukaryotic organisms. They are potentially active in diseases such as vitiligo, psoriasis, and several types of cancer. Following our interest on this type of compounds 1 four new psoralen analogues were prepared, 1a-1c and 1e. To synthesize 1a (R = H) the method of Harayama and Ishii was used where the cinnamate was obtained by the Wittig reaction followed by ring closure. Condensation of 1-formyl-2-hydroxycarbazole with diethyl malonate gave 1b which by basic hydrolysis yielded compound 1c. Compound 1d was prepared before.2 Condensation of the 2-hydroxycarbazole with ethyl acetoacetate gave 1e. The products were characterized by elemental analysis, 1H and 13C NMR. Moreover, the anti-proliferative effect of compounds 1a-1e on human cancer cell lines (MDA-MB 231, HeLa and TCCSUP) was evaluated. Results suggest that these psoralen analogues possess a potent cytotoxic effect against the cell lines studied. Computational and molecular docking studies are being carried out.Fundação para a Ciência e a Tecnologia (FCT)(PEst-C/QUI/UI0686/2011), FEDER-COMPET

New insights about the monomer and homodimer structures of the human AOX1

UID/MULTI/04378/2019. IF/01310/2013 . PhD Grant SFRH/BD/119206/2016.Human aldehyde oxidase (hAOX1) is a molybdenum dependent enzyme that plays an important role in the metabolism of various compounds either endogenous or xenobiotics. Due to its promiscuity, hAOX1 plays a major role in the pharmacokinetics of many drugs and therefore has gathered a lot of attention from the scientific community and, particularly, from the pharmaceutical industry. In this work, homology modelling, molecular docking and molecular dynamics simulations were used to study the structure of the monomer and dimer of human AOX. The results with the monomer of hAOX1 allowed to shed some light on the role played by thioridazine and two malonate ions that are co-crystalized in the recent X-ray structure of hAOX1. The results show that these molecules endorse several conformational rearrangements in the binding pocket of the enzyme and these changes have an impact in the active site topology as well as in the stability of the substrate (phthalazine). The results show that the presence of both molecules open two gates located at the entrance of the binding pocket, from which results the flooding of the active site. They also endorse several modifications in the shape of the binding pocket (namely the position of Lys893) that, together with the presence of the solvent molecules, favour the release of the substrate to the solvent. Further insights were also obtained with the assembled homodimer of hAOX1. The allosteric inhibitor (THI) binds closely to the region where the dimerization of both monomers occur. These findings suggest that THI can interfere with protein dimerization.publishe

Novel benzopsoralen analogues : synthesis, biological activity and molecular docking studies

New benzopsoralen analogues were synthesized and their inhibitory effect on the growth of tumourtumour cell lines (MDA MB231 and TCC-SUP) was evaluated. The in vitro antitumour activity of the new benzopsoralen analogues was discussed in terms of structure–activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds to evaluate the potential of these molecules to interact with the haem group of the enzymes. The results demonstrated that the compounds that are able to interact with the iron ion of the haem cofactor and at the same time with active site Asn297 are those that have better anti-proliferative activity.To the Foundation for the Science and Technology (FCT, Portugal) for financial support to the NMR Portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to the Chemistry Research Centre, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)], to REQUIMTE (PEst-C/EQB/LA0006/2011), to the Centre of Biological Engineering (PEst-OE/EQB/LA0023/2013) and the PhD grant to C.S.F. (SFRH/BD/48636/2008). The authors also acknowledge the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP, Porto, Portugal) for kindly providing the breast cancer cell lines used in this work

Synthesis of novel psoralen analogues and their in vitro antitumor activity

New tetracyclic benzofurocoumarin (benzopsoralen) analogues were synthesized and their inhibitory effect on the growth of tumor cell lines was evaluated. The human tumor cell lines used were MDA MB231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma). The in vitro antitumor activity of the new benzopsoralens was discussed in terms of structure–activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds in order to evaluate the potential of these compounds to interact with the heme group of the enzymes. The results have demonstrated that the linear compounds have the most pronounced activity against tumor cell lines and this might be related to the better accessibility that these compounds have to the active site in relation to the angular ones that have shown in the majority of the cases multiple binding poses in the active site of CYP2A6.To the Foundation for the Science and Technology (FCT, Portugal) for financial support to the NMR portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to the Research Centre, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)], (Pest-C/EQB/LA0006/2011) and the PhD grant to C.S.F. (SFRH/BD/48636/2008). The authors also acknowledge the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP, Porto, Portugal) for kindly providing the breast cancer cell line used in this work

Synthesis of novel psoralen analogues derived from 7-hydroxy-4-methylcoumarin

Fundação para a Ciência e a Tecnologia (FCT) FEDER (European Fund for Regional Development)-COMPETE-QREN-EU FCOMP-01-0124-FEDER-022716FEDER (European Fund for Regional Development)-COMPETE-QREN-EU FCOMP-01-0124-FEDER-02271

Radial collapse of carbon nanotubes for conductivity optimized polymer composites

The optimization of the electronic conduction of carbon nanotube polymer composites is studied by tuning the radial geometry of the carbon nanotubes in a compression cycle. We have investigated the structural evolution of multi-walled carbon nanotubes in a polyamide matrix as a function of applied high pressure. Combining high resolution electron microscopy and small angle neutron scattering experiments, we conclude that the nanotube radial cross-section is irreversibly deformed following applied pressures up to 5 GPa. Studying highly percolated composites we observe that the sample resistivity drastically decreases with pressure up to about 2 GPa with no further change up to the maximum 5 GPa applied pressure. An important hysteresis is observed upon decompression which leads to an enhanced electrical conductivity of the composite in all the studied compression cycles with maximum pressures ranging from 1 to 5 GPa. Modelling the radial collapse of single-walled carbon nanotubes shows that the modified radial geometry can considerably improve the electronic transport properties in contacted carbon nanotube junctions. Our results open opportunities for engineering nanotube composites by controlling the radial collapse

Laser modulated optical reflectance of thin semiconductor films on glass

Semiconductor films, deposited by reactive magnetron sputtering on glass substrates have been analyzed with the help of laser-modulated optical reflectance. The results are discussed with respect to the thermal and charge carrier transport properties. Semiconductor properties have been identified both for micro-crystalline and amorphous film

Germinação in vitro e viabilidade polínica em Passifloras silvestres.

Os programas de melhoramento genético em Passiflora utilizam, em sua maioria, as espécies silvestres como fontes de resistência a doenças. Porém, novo enfoque vem sendo dado para sua utilização como plantas ornamentais. O objetivo do trabalho foi identificar o meio adequado para a germinação in vitro de pólen de seis espécies silvestres de maracujazeiro bem como examinar a viabilidade do pólen por meio do uso do corante 2,3,5-cloreto de trifeniltetrazólio (TTC) e do lugol. O meio de cultura contendo 0,03% de Ca(NO3).4H2O, 0,02% de Mg(SO4) . 7H2O, 0,01% de KNO3, 0,01% de H3BO3, 15% de sacarose, solidificado com 0,8% de ágar e pH ajustado para 7,0, proporcionou maior percentual de grãos de pólen germinados. O corante TTC e o lugol, superestimou a viabilidade de pólen, já que todos os acessos apresentaram índice de viabilidade alto, quando comparado aos resultados obtidos in vitro

Radiopaque Crystalline, Non-Crystalline and Nanostructured Bioceramics

Radiopacity is sometimes an essential characteristic of biomaterials that can help clinicians perform follow-ups during pre- and post-interventional radiological imaging. Due to their chemical composition and structure, most bioceramics are inherently radiopaque but can still be doped/mixed with radiopacifiers to increase their visualization during or after medical procedures. The radiopacifiers are frequently heavy elements of the periodic table, such as Bi, Zr, Sr, Ba, Ta, Zn, Y, etc., or their relevant compounds that can confer enhanced radiopacity. Radiopaque bioceramics are also intriguing additives for biopolymers and hybrids, which are extensively researched and developed nowadays for various biomedical setups. The present work aims to provide an overview of radiopaque bioceramics, specifically crystalline, non-crystalline (glassy), and nanostructured bioceramics designed for applications in orthopedics, dentistry, and cancer therapy. Furthermore, the modification of the chemical, physical, and biological properties of parent ceramics/biopolymers due to the addition of radiopacifiers is critically discussed. We also point out future research lacunas in this exciting field that bioceramists can explore further