Publications

Sort by: Type [ Year  (Desc)]
2024
Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes, Choroba, Katarzyna, Zowiślok Bartosz, Kula Sławomir, Machura Barbara, Maroń {Anna M. }, Erfurt Karol, Marques Cristiana, Cordeiro Sandra, Baptista {Pedro V. }, and Fernandes {Alexandra R. } , Journal Of Medicinal Chemistry, nov, (2024) Abstract

Cu(II) complexes with 2,2':6',2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl 2(L n )]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes ( Cu1a and Cu1b) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).

Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes, Choroba, K., Zowislok B., Kula S., Machura B., Maron A. M., Erfurt K., Cordeiro S., Baptista P. V., and Fernandes {Alexandra R. } , Journal Of Medicinal Chemistry, nov, Volume 67, Number 21, p.19475–19502, (2024) Abstract

Cu(II) complexes with 2,2′:6′,2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl2(Ln)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (Cu1a and Cu1b) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).

Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes, Choroba, Katarzyna, Zowiślok Bartosz, Kula Sławomir, Machura Barbara, Maroń {Anna M. }, Erfurt Karol, Marques Cristiana, Cordeiro Sandra, Baptista {Pedro V. }, and Fernandes {Alexandra R. } , Journal Of Medicinal Chemistry, Volume 67, Number 21, p.19475–19502, (2024) Abstract

Cu(II) complexes with 2,2′:6′,2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl2(Ln)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (Cu1a and Cu1b) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).

2023
Open-source tool for real-time and automated analysis of droplet-based microfluidic, Neto, {Joana P. }, Mota Ana, c}alo Lopes Gon{\c, Coelho {Beatriz J. }, Frazão João, Moura {André T. }, Oliveira Beatriz, Sieira Bárbara, Fernandes José, Fortunato Elvira, Martins Rodrigo, Igreja Rui, Baptista {Pedro V. }, and Águas Hugo , Lab On A Chip, jul, Volume 23, Number 14, p.3238–3244, (2023) Abstract

Droplet-based microfluidic technology is a powerful tool for generating large numbers of monodispersed nanoliter-sized droplets for ultra-high throughput screening of molecules or single cells. Yet further progress in the development of methods for the real-time detection and measurement of passing droplets is needed for achieving fully automated systems and ultimately scalability. Existing droplet monitoring technologies are either difficult to implement by non-experts or require complex experimentation setups. Moreover, commercially available monitoring equipment is expensive and therefore limited to a few laboratories worldwide. In this work, we validated for the first time an easy-to-use, open-source Bonsai visual programming language to accurately measure in real-time droplets generated in a microfluidic device. With this method, droplets are found and characterized from bright-field images with high processing speed. We used off-the-shelf components to achieve an optical system that allows sensitive image-based, label-free, and cost-effective monitoring. As a test of its use we present the results, in terms of droplet radius, circulation speed and production frequency, of our method and compared its performance with that of the widely-used ImageJ software. Moreover, we show that similar results are obtained regardless of the degree of expertise. Finally, our goal is to provide a robust, simple to integrate, and user-friendly tool for monitoring droplets, capable of helping researchers to get started in the laboratory immediately, even without programming experience, enabling analysis and reporting of droplet data in real-time and closed-loop experiments.

2019
Occurrence of non-toxic bioemulsifiers during polyhydroxyalkanoate production by Pseudomonas strains valorizing crude glycerol by-product, Kourmentza, Constantina, Araújo Diana, Sevrin Chantal, Roma-Rodriques Catarina, Ferreira {Joana Lia}, Freitas Filomena, Dionisio Madalena, Baptista {Pedro V. }, Fernandes {Alexandra R. }, Grandfils Christian, and Reis {Maria A. M. } , Bioresource Technology, jun, Volume 281, p.31–40, (2019) Abstract

While screening for polyhydroxyalkanoate (PHA) producing strains, using glycerol rich by-product as carbon source, it was observed that extracellular polymers were also secreted into the culture broth. The scope of this study was to characterize both intracellular and extracellular polymers, produced by Pseudomonas putida NRRL B-14875 and Pseudomonas chlororaphis DSM 50083, mostly focusing on those novel extracellular polymers. It was found that they fall into the class of bioemulsifiers (BE), as they showed excellent emulsion stability against different hydrocarbons/oils at various pH conditions, temperature and salinity concentrations. Cytotoxicity tests revealed that BE produced by P. chlororaphis inhibited the growth of highly pigmented human melanoma cells (MNT-1) by 50% at concentrations between 150 and 200 μg/mL, while no effect was observed on normal skin primary keratinocytes and melanocytes. This is the first study reporting mcl-PHA production by P. putida NRRL B-14785 and bioemulsifier production from both P. putida and P. chlororaphis strains.

2018
Optical and Structural Characterization of a Chronic Myeloid Leukemia DNA Biosensor, Cordeiro, Mílton, Otrelo-Cardoso {Ana Rita Castro}, Svergun {Dmitri I. }, Konarev {Petr V. }, Lima {João Carlos}, Santos-Silva Teresa, and Baptista {Pedro Viana} , ACS Chemical Biology, may, Volume 13, Number 5, p.1235–1242, (2018) Abstract

Selective base pairing is the foundation of DNA recognition. Here, we elucidate the molecular and structural details of a FRET-based two-component molecular beacon relying on steady-state fluorescence spectroscopy, small-angle X-ray scattering (SAXS), microscale thermophoresis (MST), and differential electrophoretic mobility. This molecular beacon was designed to detect the most common fusion sequences causing chronic myeloid leukemia, e14a2 and e13a2. The emission spectra indicate that the self-assembly of the different components of the biosensor occurs sequentially, triggered by the fully complementary target. We further assessed the structural alterations leading to the specific fluorescence FRET signature by SAXS, MST, and the differential electrophoretic mobility, where the size range observed is consistent with hybridization and formation of a 1:1:1 complex for the probe in the presence of the complementary target and revelator. These results highlight the importance of different techniques to explore conformational DNA changes in solution and its potential to design and characterize molecular biosensors for genetic disease diagnosis.

2015
One nanoprobe, two pathogens: gold nanoprobes multiplexing for point-of-care, Veigas, Bruno, Pedrosa Pedro, Carlos {Fábio F. }, Mancio-Silva Liliana, Grosso {Ana Rita}, Fortunato Elvira, Mota {Maria M. }, and Baptista Pedro , Journal of Nanobiotechnology, aug, Volume 13, Number 1, (2015) Abstract

Background: Gold nanoparticles have been widely employed for biosensing purposes with remarkable efficacy for DNA detection. Amongst the proposed systems, colorimetric strategies based on the remarkable optical properties have provided for simple yet effective sequence discrimination with potential for molecular diagnostics at point of need. These systems may also been used for parallel detection of several targets to provide additional information on diagnostics of pathogens.Results: For the first time, we demonstrate that a single Au-nanoprobe may provide for detection of two distinct targets (pathogens) allowing colorimetric multi-target detection. We demonstrate this concept by using one single gold-nanoprobe capable to detect members of the Mycobacterium tuberculosis complex and Plasmodium sp., the etiologic agents of tuberculosis and malaria, respectively. Following characterisation, the developed gold-nanoprobe allowed detection of either target in individual samples or in samples containing both DNA species with the same efficacy.Conclusions: Using one single probe via the non-cross-linking colorimetric methodology it is possible to identify multiple targets in one sample in one reaction. This proof-of-concept approach may easily be integrated into sensing platforms allowing for fast and simple multiplexing of Au-nanoprobe based detection at point-of-need.

2014
Organometallic Compounds in Cancer Therapy: Past Lessons and Future Directions., de Fernandes, {Maria Alexandra Núncio Carvalho Ramos}, and Baptista {Pedro Miguel Ribeiro Viana} , Anti-Cancer Agents In Medicinal Chemistry, jan, Volume 14, Number 9, p.1199–1212, (2014) Abstract
n/a
2010
Optimizing Au-nanoprobes for specific sequence discrimination, DQ Group Author, Baptista {Pedro Miguel Ribeiro Viana}, and Franco Ricardo , Colloids And Surfaces B-Biointerfaces, jan, Volume 77, Number 1, p.122–124, (2010) Abstract

Gold nanoparticles functionalized with thiol-oligonucleotides are ideal platforms for detection of specific DNA sequences. Here we evaluate the effect of single base mismatches in hybridization efficiency according to the position of the mismatch, base pairing combination and thiol-oligonucleotide density in terms of specificity and efficiency of target recognition. Hybridization efficiency and single-nucleotide polymorphism discrimination at room temperature is maximized at a density of 83 +/- 4 thiol-oligonucleotides per 13.5 nm gold nanoparticle (24 pmol/cm(2)), and when the mismatch is localized at the 3'-end of the Au-nanoprobe, i.e. away from the gold nanoparticle surface. (C) 2010 Elsevier B.V. All rights reserved.

loading