Carla Rios-Luci

• KU Leuven

Cancer immunotherapy is often hindered by an immunosuppressive tumor microenvironment (TME). Various strategies are being evaluated to shift the TME from an immunologically ‘cold’ to ‘hot’ tumor and hereby improve current immune checkpoint blockades (ICB). One particular hot topic is the use of combination therapies. Here, we set out to screen a va...

Cancer immunotherapy is often hindered by an immunosuppressive tumor microenvironment (TME). Various strategies are being evaluated to shift the TME from an immunologically ‘cold’ to ‘hot’ tumor and hereby improve current immune checkpoint blockades (ICB). One particular hot topic is the use of combination therapies. Here, we set out to screen a va...

The ability to improve nanoparticle delivery to solid tumors is an actively studied domain, where various mechanisms are looked into. In previous work, the authors have looked into nanoparticle size, tumor vessel normalization, and disintegration, and here it is aimed to continue this work by performing an in‐depth mechanistic study on the use of c...

Nanoparticle delivery to solid tumors is known to be an inefficient process and various studies have tried to increase efficacy, but mechanistic and comparative studies remain scarce. Here, we use pharmacological agents to study the effect of vessel normalization or vessel disintegration on nanoparticle delivery to solid tumors. Using a multiparame...

Nanoparticle-mediated cancer immunotherapy holds great promise, but more efforts are needed to obtain nanoformulations that result in a full scale activation of innate and adaptive immune components that specifically target the tumors. We generated a series of copper-doped TiO2 nanoparticles in order to tune the kinetics and full extent of Cu²⁺ ion...

Nanoparticle (NP) delivery to solid tumors remains an actively studied field, where several recent studies have shed new insights into the underlying mechanisms and the still overall poor efficacy. In the present study, Au NPs of different sizes were used as model systems to address this topic, where delivery of the systemically administered NPs to...

Microtubule targeting agents (MTAs) are extensively used in cancer treatment and many have achieved substantial clinical success. In recent years, targeting microtubules to inhibit cell division has become a widespread pharmaceutical approach for treatment of various cancer types. Nevertheless, the development of multidrug resistance (MDR) in cance...

The progress in nanomedicine (NM) using nanoparticles (NPs) is mainly based on drug carriers for the delivery of classical chemotherapeutics. As low NM delivery rates limit therapeutic efficacy, an entirely different approach was investigated. A homologous series of engineered CuO NPs was designed for dual purposes (carrier and drug) with a direct...

The controlled dissolution kinetics of iron‐doped copper oxide nanoparticles are applied in targeted nanomedicine. In their Research Article (DOI: 10.1002/anie.201912312), L. Mädler, S. J. Soenen et al. present a model‐based approach for adjusting the dissolution kinetics and intracellular release of copper that opens a therapeutic window for cance...

Die kontrollierte Auflösungskinetik Eisen‐dotierter Kupferoxid‐Nanopartikel wird in der gezielten Nanomedizin eingesetzt. In ihrem Forschungsartikel (DOI: 10.1002/ange.201912312) stellen L. Mädler, S. J. Soenen et al. einen Modell‐basierten Ansatz zur Anpassung der Auflösungskinetik und interzellulären Freigabe von Kupfer vor, der neue Krebstherapi...

The progress in nanomedicine (NM) using nanoparticles (NPs) is mainly based on drug carriers for the delivery of classical chemotherapeutics. While low NM delivery rates limit therapeutic efficacy, an entirely different approach was investigated. A homologous series of engineered CuO NPs was designed for dual purpose (carrier and drug) with a direc...

Small molecule inhibitors (TKIs) of HER2 have demonstrated clinical benefit in HER2-positive breast tumors. One of them, lapatinib, is used once advanced tumors become refractory to the HER2 antibody trastuzumab. Another one, neratinib, has shown benefit in high-risk early-stage breast cancer after trastuzumab-based therapies. A common characterist...

The appearance of resistance to the anti-HER2 targeted drug trastuzumab constitutes, nowadays, an important challenge in the oncology clinic. To fight such resistance, we searched for potential vulnerabilities in cells resistant to that drug. To that end, we used cell lines primary resistant to trastuzumab, as well as cells made secondarily resista...

In the scenario of drug discovery, numerous in vitro testing initiatives had been established. Thus far, no general methodology is reputable and literature on this hot topic is scarce. In this respect, we propose a strategy based on a Phenotypic Drug Discovery approach. Within our program directed at the discovery of new antitumor agents, we have f...

Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) that was approved recently to treat HER2+ breast cancers. Despite its impressive clinical efficacy in many patients, intrinsic and acquired resistance to T-DM1 has emerged as a challenge. To identify mechanisms of T-DM1 resistance, we isolated several resistant HER2+ clones exhibitin...

The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently report...

Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the indu...

The antiproliferative activities of a series of 36 naphthoquinone derivatives were subjected to a Quantitative Structure-Activity Relationships (QSAR) study. For this purpose a panel of four human cancer cell lines was used, namely HBL-100 (breast), HeLa (cervix), SW-1573 (non-small cell lung) and WiDr (colon). A conformation-independent representa...

In this communication, we present the synthesis of new platinum complexes based on hydroxyquinoline ligands. We demonstrate the importance and the role of the halogen substitution as well as the chelation, which are essential structural characteristics for finding good cytotoxicities.

Having identified a novel human DNA topoisomerase IIα (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the correspondi...

In this manuscript, we describe the synthesis of new trans-N-sulfonamide platinum complexes and their antiproliferative activity (GI50, μM) in human solid tumors cells. The structure activity relationships (SAR), with different new synthesized complexes by variation in ligand, halogen and also in the stereochemistry of the ligand, has been studied....

Background Despite our increased understanding of the mechanisms involved in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), there is no specific pharmacological treatment of proven benefit. We used a novel screening methodology to examine potential anti-inflammatory effects of a small structure-focused library of synthe...

Trypan blue exclusion assay. The percentage of viable and non-viable cells in A549 and BEAS-2B cell populations after treatment with 100 ng/mL E. coli LPS in the presence or absence of different concentrations of CKT0103 (0-0.1-1-10-100-1000 µM) for 18 hours. ***p<0.001 vs. control (C); † p<0.001 vs. LPS. (TIF)

Chemical structure of natural and synthetic compounds and percentage of survival (PS) of A549 and BEAS-2B cells stimulated with 100 ng/mL E. coli LPS in combination with: 1a–c: pyrimidinyl carbamates; 2a–h: pyrimidinyl ureas; R = chemical structure. (DOC)

Survival curves of A549 and BEAS-2B cells after 6, 12 and 18 hours of 0.1-1.0-10-100 ng/mL E. coli LPS stimulation. We used A549 and BEAS-2B cells as control-vehicle (C) cells incubated in the presence of vehicle-0.5% (v/v) DMSO. The values reported for E. coli LPS concentrations have been normalized to those for untreated (no LPS) control-vehicle...

(DOC)

Selective acid-promoted cyclization of lapachols (I) affords the α- (III) and β-lapachones (II), respectively.

In this study, we synthesized a series of phenylpropanoic acid derivatives based on modifications at four selected points of the molecular scaffold. The in vitro antiproliferative activities of the compounds were examined in representative human solid tumor cell lines. A SAR was established pointing out the relevance of the substituents. The best a...

In this study, we describe the synthesis of a series of α- and β-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-β-lapachone as lead with en...

Three withanolides were isolated from the aerial parts of Jaborosa reflexa Phil. Jaborosa cabrerae Barboza yielded five sativolide withanolides (including jaborosalactones R, S, 38, and 39) and two trechonolide withanolides epimeric at C-23 (trechonolide A and jaborosalactone 32). In addition, five derivatives were obtained by chemical derivatizati...

DTA0100 is a new catalytic inhibitor of the human DNA topoisomerase IIα that induces G2/M phase cell cycle arrest in human solid tumor cells lines from various malignancies. In our study, we investigated the effectiveness of the combined treatment of ionizing radiation with DTA0100 on the survival of three representative human solid tumor cell line...

Six diiodido-diamine platinum(II) complexes, either cis or trans configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effect...

A new family of heterometallic compounds 3-6 containing ferrocenyl and platinum(II) centers has been synthesized by reaction of 1-β-aminoethylferrocene (1) and 1,1'-bis(β-aminoethyl)ferrocene (2) with Pt(II) precursors. Using K(2)[PtCl(4)] as the Pt(II) source, the cis-square-planar neutral compounds [Fe{η(5)-C(5)H(4)(CH(2))(2)NH(2)}(2)PtCl(2)] (3)...

A Phenotypic Drug Discovery strategy was applied to study a set of pyrimidine analogs prepared by means of intramolecular oxidation-reduction reactions of N-substituted-N-(2,6-disubstituted-5-nitro-4-pyrimidinyl)aminoacetic acid methyl esters in basic media. The combined and rational use of specific assays allowed in short time reducing from all po...

In this work, we described for the first time the synthesis of trans-N-sulfonamide platinum complexes. The antiproliferative activity (GI(50), mu M) of these new compounds in human solid tumors cells was compared to cisplatin.

The biological evaluation of new Ru(II) complexes carrying dmoPTA (dmoPTA=3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) ligands is reported. The results on the biological activity revealed that the organometallic complexes are active against all cell lines with GI(50) values in the range 1.1-2.6 μM. When compared to the standard anticanc...

A sequential transformation based on the titanium-mediated aldol addition of (S)-1-bromo-3-(tert-butyldimethylsilyloxy)-2-butanone, a chiral lactate-derived ketone, to tetradecanal followed by reduction of the ensuing aldolate afforded the corresponding syn-1,3-diol as a single diastereomer. Debromination and further manipulation of this intermedia...

In this work, we described for the first time the synthesis of trans-N-sulfonamide platinum complexes. The antiproliferative activity (GI50, mM) of these new compounds in human solid tumors cells was compared to cisplatin.

Six diiodido-diamine platinum(II) complexes, either cis or trans configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects...

Investigation of the organic extracts of the roots of Maytenus vitis-idaea and Maytenus spinosa, collected in the province of Salta, Argentina, led to isolation of eighteen compounds belonging to several classes. From M. vitis-idaea, eight methylenequinone celastroids (1-8) were isolated, four of which (4-7) were hitherto unknown. Additionally, fro...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A small structure-focused library of propargylic enol ethers was prepared by means of a modular and efficient chemodifferentiating organocatalyzed multicomponent reaction. The most active compound (GI(50) 0.25 microM) against solid tumor cells was selected as lead. Cell cycle analysis and immunoblotting demonstrated arrest at the metaphase, pointin...

The generation of diversity‐oriented libraries is a valuable tool for the discovery of new anticancer agents. The objective was to evaluate the anti‐proliferative activity of a set of 27 propargylic enol ethers derivatives in cancer cells. The antiproliferative activity was performed against the human solid tumor cell lines SW1573, HBL‐100 and HeLa...

A series of 2-substituted 1,2-dihydro-3-phenyl-1-(trichloromethyl)benzo[b][1,6]naphthyridines were synthesized and their in vitro antiproliferative activities were examined against human solid tumor cell lines and relevant strains of bacteria and Candida. The compounds induced considerably growth inhibition in all cancer cell lines, whilst showed i...

Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed alpha-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38-1.86muM. Cell cycle studies for the...

A series of 2,4-disubstituted 6-aryl-7H-pyrrolo[3,2-d]pyrimidin-7-one 5-oxides were synthesized and in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, HBL-100, HeLa, SW1573, T-47D, and WiDr. The most potent analog induced considerably growth inhibition in the range 0.35-2.0microM. Cell cycle studies in th...