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

We describe the synthesis of 3H-benzofuro[3,2-f]chromen-3-ones. The anti-proliferative effect on human cancer cell lines (MDA-MB231 and HeLa) was evaluated.FCT and FEDER, for National NMR Networ

Synthesis and characterization of psoralen analogues based on carbazoles

Novel psoralen analogues based on carbazoles were synthesized and characterized.Fundação para a Ciência e Tecnologia (FCT) and FEDER, for National NMR Networ

Synthesis and characterization of psoralen analogues based on dibenzofuran

Fundação para a Ciência e Tecnologia (FCT) and FEDER, for National NMR Networ

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

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

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

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 tacrine analogues derived from n-aryl-5-amino-4-cyanopyrazoles

Synthesis of eleven tacrine analogues derived from N-aryl-5-amino-4-cyanopyrazoles, by a Friedländer type reaction, is described. Their structures were confirmed by 1H and 13C NMR spectroscopy, elemental analysis and/or mass spectrometry.Fundação para a Ciência e Tecnologia and FEDER (POCTI-SFA-3-686

Controlling Macrophage Polarization to Modulate Inflammatory Cues Using Immune-Switch Nanoparticles

The persistence of inflammatory mediators in tissue niches significantly impacts regenerative outcomes and contributes to chronic diseases. Interleukin-4 (IL4) boosts pro-healing phenotypes in macrophages (MÏ ) and triggers the activation of signal transducer and activator of transcription 6 (STAT6). Since the IL4/STAT6 pathway reduces MÏ responsiveness to inflammation in a targeted and precise manner, IL4 delivery offers personalized possibilities to overcome inflammatory events. Despite its therapeutic potential, the limited success of IL4-targeted delivery is hampered by inefficient vehicles. Magnetically assisted technologies offer precise and tunable nanodevices for the delivery of cytokines by combining contactless modulation, high tissue penetration, imaging features, and low interference with the biological environment. Although superparamagnetic iron oxide nanoparticles (SPION) have shown clinical applicability in imaging, SPION-based approaches have rarely been explored for targeted delivery and cell programming. Herein, we hypothesized that SPION-based carriers assist in efficient IL4 delivery to MÏ , favoring a pro-regenerative phenotype (M2Ï ). Our results confirmed the efficiency of SPION-IL4 and MÏ responsiveness to SPION-IL4 with evidence of STAT6-mediated polarization. SPION-IL4-treated MÏ showed increased expression of M2Ï associated-mediators (IL10, ARG1, CCL2, IL1Ra) when compared to the well-established soluble IL4. The ability of SPION-IL4 to direct MÏ polarization using sophisticated magnetic nanotools is valuable for resolving inflammation and assisting innovative strategies for chronic inflammatory conditions.This research was funded by the European Research Council, Consolidator Grant Magtendon, grant number 772817. FCT-Fundação para a Ciência e a Tecnologia, grant number SFDH/BD/144816/2019. FCT-Fundação para a Ciência e a Tecnologia under the Scientific Employment Stimulus—Individual Call: 2020.01157.CEECIND