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Re-Use of Caco-2 Monolayers in Permeability Assays—Validation Regarding Cell Mo...

Pires, Cristiana L.; Praça, Catarina; Martins, Patrícia A. T.; Batista de Carvalho, Ana L. M.; Ferreira, Lino; Catarro, Maria Paula M. Marques

Caco-2 monolayers are a common in vitro model used to evaluate human intestinal absorption. The reference protocol requires 21 days post-seeding to establish a stable and confluent cell monolayer, which is used in a single permeability assay during the period of monolayer stability (up to day 30). In this work, we characterize variations in the tightness of the cell monolayer over the stable time interval and e...


Impact of the Pd2Spm (Spermine) Complex on the Metabolism of Triple-Negative Br...

Carneiro, Tatiana J.; Araújo, Rita; Vojtek, Martin; Gonçalves-Monteiro, Salomé; Batista de Carvalho, Ana L. M.; Marques, Maria Paula M.; Diniz, Carmen

The interest in palladium(II) compounds as potential new anticancer drugs has increased in recent years, due to their high toxicity and acquired resistance to platinum(II)-derived agents, namely cisplatin. In fact, palladium complexes with biogenic polyamines (e.g., spermine, Pd2Spm) have been known to display favorable antineoplastic properties against distinct human breast cancer cell lines. This study descri...


Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential An...

Carneiro, Tatiana J.; Araújo, Rita; Vojtek, Martin; Gonçalves-Monteiro, Salomé; Diniz, Carmen; Batista de Carvalho, Ana L. M.; Marques, Maria Paula M.

Pd(II)-compounds are presently regarded as promising anticancer drugs, as an alternative to Pt(II)-based drugs (e.g., cisplatin), which typically trigger severe side-effects and acquired resistance. Dinuclear Pd(II) complexes with biogenic polyamines such as spermine (Pd2Spm) have exhibited particularly beneficial cytotoxic properties, hence unveiling the importance of understanding their impact on organism met...


Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as ...

Martins, Ana S.; Batista de Carvalho, Ana L. M.; Marques, Maria Paula M.; Gil, Ana M

This paper reports the first metabolomics study of the impact of new chelates Pt2Spm and Pd2Spm (Spm = Spermine) on human osteosarcoma cellular metabolism, compared to the conventional platinum drugs cisplatin and oxaliplatin, in order to investigate the effects of different metal centers and ligands. Nuclear Magnetic Resonance metabolomics was used to identify meaningful metabolite variations in polar cell ext...


Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Pallad...

Vojtek, Martin; Gonçalves-Monteiro, Salomé; Pinto, Edgar; Kalivodová, Sára; Almeida, Agostinho; Marques, Maria P. M.; Batista de Carvalho, Ana L. M.

Palladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinet...


Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Pallad...

Vojtek, Martin; Gonçalves-Monteiro, Salomé; Pinto, Edgar; Kalivodová, Sára; Almeida, Agostinho; Marques, Maria P. M.; Batista de Carvalho, Ana L. M.

Palladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinet...


A New Look into the Mode of Action of Metal-Based Anticancer Drugs

Marques, Maria P. M.; Batista de Carvalho, Ana L. M.; Mamede, A. P.; Dopplapudi, Asha; Rudić, Svemir; Tyagi, Madhusudan; Garcia Sakai, Victoria

The mode of action of Pt- and Pd-based anticancer agents (cisplatin and Pd2Spm) was studied by characterising their impact on DNA. Changes in conformation and mobility at the molecular level in hydrated DNA were analysed by quasi-elastic and inelastic neutron scattering techniques (QENS and INS), coupled to Fourier transform infrared (FTIR) and microRaman spectroscopies. Although INS, FTIR and Raman revealed dr...


Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisp...

Carneiro, Tatiana J.; Araújo, Rita; Vojtek, Martin; Gonçalves-Monteiro, Salomé; Diniz, Carmen; Batista de Carvalho, Ana L. M.; Marques, Maria Paula

This work describes, to our knowledge, the first NMR metabolomics analysis of mice kidney, liver, and breast tissue in response to cisplatin exposure, in search of early metabolic signatures of cisplatin biotoxicity. Balb/c mice were exposed to a single 3.5 mg/kg dose of cisplatin and then euthanized; organs (kidney, liver, breast tissue) were collected at 1, 12, and 48 h. Polar tissue extracts were analyzed by...


Bioinspired-Metalloporphyrin Magnetic Nanocomposite as a Reusable Catalyst for ...

Dias, Lucas D.; Batista de Carvalho, Ana L. M.; Pinto, Sara M. A.; Aquino, Gilberto L. B.; Calvete, Mário J. F.; Rossi, Liane M.; Marques, Maria Paula

In the present study, we developed a green epoxidation approach for the synthesis of the diastereomers of (-)-isopulegol benzyl ether epoxide using molecular oxygen as the oxidant and a hybrid manganese(III)-porphyrin magnetic reusable nanocomposite as the catalyst. High activity, selectivity, and stability were obtained, with up to four recycling cycles without the loss of activity and selectivity for epoxide....


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