A5072472177- Drug Transport and Resistance Mechanisms
- Cancer therapeutics and mechanisms
- Bioactive Natural Diterpenoids Research
- HIV/AIDS drug development and treatment
- Natural product bioactivities and synthesis
- DNA and Nucleic Acid Chemistry
- Plant-based Medicinal Research
- Antibiotic Resistance in Bacteria
- Metal complexes synthesis and properties
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Antibiotics Pharmacokinetics and Efficacy
- Power System Reliability and Maintenance
- Drug Solubulity and Delivery Systems
- Protein Structure and Dynamics
- Microgrid Control and Optimization
- Electric Vehicles and Infrastructure
- Advanced Battery Technologies Research
- Crystallization and Solubility Studies
- Pharmacological Effects and Toxicity Studies
- Bioactive Compounds and Antitumor Agents
- Bacterial Identification and Susceptibility Testing
- Plant biochemistry and biosynthesis
- Phytochemistry and Biological Activities
- Electric Power System Optimization
University of Lisbon
2013-2025
AbbVie (United States)
2025
AbbVie (Japan)
2025
Red Glead Discovery (Sweden)
2021-2023
Medicon Village
2021-2023
Uppsala University
2019-2021
Science for Life Laboratory
2019-2020
Universidade Nove de Julho
2018
INESC TEC
2013-2017
Universidade do Porto
2009-2016
P-Glycoprotein (Pgp) is one of the best characterized ABC transporters, often involved in multidrug-resistance phenotype overexpressed by several cancer cell lines. Experimental studies contributed to important knowledge concerning substrate polyspecificity, efflux mechanism, and drug-binding sites. This information is, however, scattered through different perspectives, not existing a unifying model for available this transporter. Using previously refined structure murine Pgp, three putative...
P-Glycoprotein (P-gp) is often involved in multidrug resistance (MDR) to the pharmacological action of a wide number anticancer agents. In this article, series molecular dynamics simulations murine's P-gp were developed, elucidating importance lipid membrane and linker sequence protein structure stability. The behavior several molecules inside drug-binding pocket revealed striking difference between substrates or modulators, motion patterns identified that could be correlated with...
The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2–13) and hydrolysis compound 14. vitro modulation P-gp compounds 1–14 was evaluated through combination transport chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with human MDR1 gene. Apart from D, all (2–14) showed potential as MDR reversal agents. In this small library novel bioactive macrocyclic lathyrane...
Efflux pumps of the ATP-binding cassette transporters superfamily (ABC transporters) are frequently involved in multidrug-resistance (MDR) phenomenon cancer cells. Herein, we describe a new atomistic model for MDR-related ABCG2 efflux pump, also named breast resistance protein (BCRP), based on recently published crystallographic structure ABCG5/G8 heterodimer sterol transporter, member ABCG family cholesterol homeostasis. By means molecular dynamics simulations and docking, far-reaching...
Crossing the Gram-negative bacterial membrane poses a major barrier to antibiotic development, as many small molecules that can biochemically inhibit key processes are rendered microbiologically ineffective by their poor cellular uptake. The outer is permeability for drug-like molecules, and chemical properties enable efficient uptake into mammalian cells fail predict We have developed computational method accurate prospective prediction of which we combine with new medium-throughput...
Bidirectional and efficient on-board charger systems for electric vehicles is a challenge nowadays. This paper describes novel power converter system that implements bidirectional flow between the grid an vehicle battery, where dual active bridge advantageous. With topology proper control all major constraints, such as quality, harmonic rejection, reactive control, others, can be easily satisfied. A hardware prototype of built. Experimental results from this verify preliminary operation...
Multidrug resistance related to the increased expression of P-glycoprotein (P-gp) by cancer cells is major contributor for failure chemotherapeutic treatments. Starting from pharmacophores and data already published in macrocyclic diterpenes isolated Euphorbia species, a comprehensive study pharmacophore definitions features was performed order obtain new improved four-point able detect literature in-house modulators simultaneously specific enough avoid detection most nonactive molecules...
The phytochemical study of Euphorbia pedroi led to the isolation a new tetracyclic triterpenoid with an unusual spiro scaffold, spiropedroxodiol (1), along seven known terpenoids (2–8). Aiming at obtaining compounds improved multidrug-resistance (MDR) reversal activity, compound 8, ent-abietane diterpene, was derivatized by introducing nitrogen-containing and aromatic moieties, yielding 9–14. structures were characterized detailed spectroscopic analysis, including 2D NMR experiments (COSY,...
O descolamento de retina associado à toxoplasmose ocular é uma complicação rara, mas grande relevância clínica devido ao impacto potencial na visão e qualidade vida dos pacientes. Esta revisão abrangente aborda os aspectos anatômicos, funcionais terapêuticos dessa condição, destacando principais fatores risco, complicações desfechos clínicos. Foram analisados estudos manejo cirúrgico, como vitrectomia via pars plana retinopexia pneumática, que apresentam alta eficácia no fechamento retiniano...
Aim: Naringenin (1), isolated in large amount from the aerial parts of Euphorbia pedroi, was chemically derivatized to yield 18 imine derivatives (2–19) and three alkylated through a Mannich-type reaction (20–22) that were tested as multidrug resistance (MDR) reversers cancer cells. Results/methodology: While hydrazone (2–4) azine (5–13) showed an improvement their MDR reversal activities against breast protein, carbohydrazides 14–19 revealed enhancement activity toward protein 1....
Pedrolide (1), a diterpenoid with an unprecedented carbon skeleton, pedrolane, containing bicycle[2.2.1]heptane system, is reported. This structural feature hypothesized to involve intramolecular cyclization, via Michael addition, and ring contraction, 1,2-alkyl shift or Pinacol rearrangement of rings A B, from tigliane-type 5/7/6/3-tetracyclic precursor. The structure 1 was established using spectroscopic techniques, single-crystal X-ray diffraction, ab initio calculations. reversed...
One of the greatest threats to cancer treatment is development, by some tumors, resistance pharmacological action several structurally unrelated cytotoxic agents—multidrug (MDR). As P‐glycoprotein (P‐gp) one most studied ATP‐dependent efflux pumps that are frequently involved in drug from cells, development MDR modulators with ability inhibit P‐gp considered a promising approach for overcoming MDR. However, have been hampered due absence knowledge on intrinsic molecular aspects which occurs,...
The development of multidrug resistance (MDR) is a major cause failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6β-hydroxyroyleanone (AHR, 2). royleanone derivatives were prepared through hemisynthesis natural compounds 1 2 to achieve small library products enhanced anti-P-glycoprotein activity. Nonetheless, some tend be unstable. Therefore, reason lack...
The P-glycoprotein efflux mechanism is being studied since its identification as a leading protagonist in multidrug resistance. Recently, it was suggested that drugs enter the drug-binding pocket (DBP) through gates located between transmembrane domains. For both substrate and modulator, potential of mean force curves along reaction coordinate obtained with WHAM approach were similar, no activation energy required for crossing gate. Moreover, drug transit from bulk water into DBP...
Multidrug resistance (MDR) has been regarded as one of the major hurdles for successful outcome cancer chemotherapy. The collateral sensitivity (CS) effect is most auspicious anti-MDR strategies. Epoxylathyrane derivatives 1-16 were obtained by derivatization macrocyclic diterpene epoxyboetirane A (17), a lathyrane-type isolated from Euphorbia boetica. Some these compounds found to strongly modulate P-glycoprotein (P-gp/ABCB1) efflux.The main goal was develop diterpenes with improved...
Abstract P-glycoprotein (P-gp, ABCB1) overexpression is, currently, one of the most important multidrug resistance (MDR) mechanisms in tumor cells. Thus, modulating drug efflux by P-gp has become promising approaches to overcome MDR cancer. Yet, more insights on molecular basis specificity and efflux-related signal transmission mechanism between transmembrane domains (TMDs) nucleotide binding (NBDs) are needed develop molecules with higher selectivity efficacy. Starting from a murine...
Cancer is among the leading causes of death worldwide. One most challenging obstacles in cancer treatment multidrug resistance (MDR). Overexpression P-glycoprotein (P-gp) associated with MDR. The growing incidence and development MDR drive search for novel more effective anticancer drugs to overcome problem. Royleanones are natural bioactive compounds frequently found Plectranthus spp. cytotoxic diterpene 6,7-dehydroroyleanone ( 1 ) main component P. madagascariensis (Pers.) Benth. essential...