Article
Chemistry, Medicinal
Jing Yang, Lei Chen, Peng-Chao Wang, Bo Yang, Chuan-Zhu Gao
Summary: This study developed a series of cyclometalated platinum (II) complexes with near-infrared phosphorescent emission targeting carbonic anhydrase IX (CAIX). These complexes showed high binding affinity and effective inhibition on CAIX in vitro. The complexes demonstrated significantly enhanced therapeutic effect on multiple cancer cell lines compared to cisplatin and had higher selectivity towards cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Javier E. Lopez-Hernandez, Nazia Nayeem, Jose P. Ceron-Carrasco, Afruja Ahad, Aiman Hafeez, Ignacio E. Leon, Maria Contel
Summary: This study describes new heterometallic binuclear and trinuclear platinum(IV)-gold(I) compounds that exhibit cytotoxicity and selectivity against a small panel of cancer cell lines. One trinuclear compound accumulates in the nucleus and mitochondria, induces apoptosis, and shows antimigratory and antiangiogenic properties against triple-negative breast cancer (TNBC) cell lines, as well as potent cytotoxic effect against TNBC 3D spheroids.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Inorganic & Nuclear
Yan-Bo Peng, Wei He, Qiang Niu, Can Tao, Xiao-Lan Zhong, Cai-Ping Tan, Ping Zhao
Summary: Inorganic medicinal chemistry has largely focused on platinum or ruthenium, with insufficient research on other metal centers such as rhodium. This study synthesized a series of cyclometalated rhodium(iii) complexes, which showed stronger anticancer activity than cisplatin. Mechanistic studies revealed that these complexes induced cellular apoptosis through mitochondrial pathways by causing severe damage and cell cycle arrest.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Inorganic & Nuclear
Sergej Stipurin, Thomas Strassner
Summary: A total of six novel platinum complexes were successfully synthesized from saturated N-heterocyclic carbene precursors, showing strong emissive properties in the sky-blue region of the visible spectrum with quantum yields up to 71% in a PMMA matrix. The structures were characterized by NMR experiments and solid-state analyses, confirming the cyclometalation and saturated backbone of the NHC motif. DFT calculations were used to examine the photophysical and electrochemical properties of the platinum complexes.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Sergej Stipurin, Thomas Strassner
Summary: The synthesis of N-heterocyclic carbene precursors and their cyclometalated platinum(II) carbene complexes based on hexahydroimidazo[1,5-a]pyridine are reported in this study. The properties of these platinum complexes were characterized by various techniques, and their photophysical and electrochemical behaviors were investigated. Quantum chemical calculations were used to rationalize the experimental results.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Nazia Nayeem, Arefa Yeasmin, Samantha N. Cobos, Ali Younes, Karen Hubbard, Maria Contel
Summary: The study evaluated the effects of a water-soluble organometallic ruthenium compound Ru-IM (1) on TNBC cell lines derived from patients of European and African ancestry, showing high cytotoxicity and potential anti-metastatic and anti-angiogenic properties. The compound was found to inhibit protein expression of cytokine M-CSF involved in the PI3/AKT pathway, and demonstrated a p53-independent mechanism of action.
Article
Chemistry, Inorganic & Nuclear
Tania Zhivkova, Daniela C. Culita, Abedulkadir Abudalleh, Lora Dyakova, Teodora Mocanu, Augustin M. Madalan, Milena Georgieva, George Miloshev, Anamaria Hanganu, Gabriela Marinescu, Radostina Alexandrova
Summary: In this study, two families of homo- and heterometallic complexes were synthesized and their cytotoxic and genotoxic effects on different types of cells were investigated. The results showed that these compounds could significantly inhibit the growth and proliferation of cells within a certain concentration range, with the complexes containing Au(I) exhibiting higher cytotoxic and genotoxic activity. Some of the complexes also showed more pronounced cytotoxic potential than commercially available antitumor agents.
DALTON TRANSACTIONS
(2023)
Review
Chemistry, Medicinal
Suxing Jin, Yan Guo, Zijian Guo, Xiaoyong Wang
Summary: Monofunctional platinum(II) complexes are a class of non-traditional anticancer agents hopeful to overcome the defects of current platinum drugs, with designs aiming to visualize cellular distribution, reduce side effects, improve tumor selectivity, or inhibit cancer cells through non-DNA targets.
Article
Biochemistry & Molecular Biology
Brondwyn S. McGhie, Jennette Sakoff, Jayne Gilbert, Christopher P. Gordon, Janice R. Aldrich-Wright
Summary: Cancer is a significant global health threat and new treatments are needed to improve patient prognosis. Unconventional platinum complexes, consisting of polypyridyl ligands and diaminocyclohexane, have shown anticancer activity in previously undruggable KRAS mutated cells, with cytotoxicity values up to 100 times better than cisplatin. Inspired by these complexes, six novel cyclometallated examples were designed and their fluorescence was used to study the mechanism of action of platinum drugs. The cytotoxicity results showed that these cyclometallated complexes have different activity compared to the inspiring complexes, but are as cytotoxic as cisplatin and have higher selectivity indices in breast cancer cell lines. Complexes 1b, 2a, and 3b exhibited particularly high selectivity indexes. Further investigation revealed their good affinity to ctDNA, especially CMCs 1a and 3b. The fluorescence of these complexes was successfully utilized in calculating their DNA binding affinity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Adedamola S. Arojojoye, Breyanna Walker, James C. Dawahare, Maame Abena O. Afrifa, Sean Parkin, Samuel G. Awuah
Summary: Optimizing the bioavailability of metal-derived chemotherapeutic agents is crucial for successful drug development. Nanoparticle delivery strategies can improve bioavailability, pharmacokinetics, efficacy, and minimize toxicity. Using biodegradable albumin nanoconstructs to deliver gold(III) complexes improved solubility, intracellular accumulation, and anticancer activity.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Dominique Roberto, Alessia Colombo, Claudia Dragonetti, Francesco Fagnani, Massimo Cocchi, Daniele Marinotto
Summary: Substitution of the chlorido ligand with 4-phenylthiazole-2-thiolate leads to thiolato complexes with tunable emission color and high luminescence quantum yield.
Article
Materials Science, Multidisciplinary
Mikhail Dobrynin, Elina Sokolova, Mikhail A. Kinzhalov, Andrey S. Smirnov, Galina L. Starova, Vadim Yu Kukushkin, Regina M. Islamova
Summary: In this study, a family of platinum complexes were synthesized and used as hydrosilylation catalysts to prepare luminescent silicone rubbers. The silicone rubbers and the complexes exhibited similar emission spectra in the green region and strong phosphorescence, with potential applications in protective coatings and phosphor-converted white light-emitting diodes.
ACS APPLIED POLYMER MATERIALS
(2021)
Review
Chemistry, Multidisciplinary
Julien Monot, Enrico Marelli, Blanca Martin-Vaca, Didier Bourissou
Summary: The chemistry of (P,C)-cyclometalated complexes derived from naphthyl phosphines [(Np)(P,C)M] is reviewed and analysed in this paper. The three main synthetic approaches, P-chelation assisted C-H activation, oxidative addition and transmetalation, are described and compared. These complexes exhibit high thermal and chemical robustness, and have been shown to be competent catalysts in various transformations, as well as key intermediates in others.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Nanoscience & Nanotechnology
Adedamola S. Arojojoye, Breyanna Walker, James C. Dawahare, Maame Abena O. Afrifa, Sean Parkin, Samuel G. Awuah
Summary: Optimizing the bioavailability of metal-derived chemotherapeutic agents is crucial for successful drug development. Nanoparticle delivery strategies can improve solubility and anticancer activity of metal drugs, with potential translational benefits in the clinic.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Inorganic & Nuclear
Sergej Stipurin, Thomas Strassner
Summary: Three different imidazolylidene ligand precursors with methyl groups in 4- and 5-position were synthesized to build a series of nine cyclometalated platinum(II) complexes, using β-diketonate and bis(pyrazolyl)borate motifs as auxiliary ligands. The synthesized platinum complexes exhibit room temperature phosphorescence in a PMMA matrix with high quantum yields and specific color coordinates. Additional insight into the properties of these compounds was gained through quantum chemical calculations and electrochemical experiments.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Bart Hens, Isabel Gonzalez-Alvarez, Marival Bermejo
Summary: This review presents the applications and future perspectives of the in situ perfusion technique for studying drug absorption mechanisms. The differences in gastrointestinal anatomy and physiology between rats and humans are thoroughly discussed.
MOLECULAR PHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Georgiana Crainiciuc, Miguel Palomino-Segura, Miguel Molina-Moreno, Jon Sicilia, David G. Aragones, Jackson Liang Yao Li, Rodrigo Madurga, Jose M. Adrover, Alejandra Aroca-Crevillen, Sandra Martin-Salamanca, Alfonso Serrano del Valle, Sandra D. Castillo, Heidi C. E. Welch, Oliver Soehnlein, Mariona Graupera, Fatima Sanchez-Cabo, Alexander Zarbock, Thomas E. Smithgall, Mauro Di Pilato, Thorsten R. Mempel, Pierre-Louis Tharaux, Santiago F. Gonzalez, Angel Ayuso-Sacido, Lai Guan Ng, Gabriel F. Calvo, Ivan Gonzalez-Diaz, Fernando Diaz-de-Maria, Andres Hidalgo
Summary: Transcriptional and proteomic profiling of individual cells have provided cellular landscapes of tissues, but fail to capture dynamic scenarios. This study used live imaging to record morpho-kinetic parameters of leukocytes in active inflammation and built behavioural landscapes that identified leukocyte identities and revealed a continuum of neutrophil states. Mutant screening identified the kinase Fgr as a driver of pathogenic inflammation, and interfering with Fgr protected mice from inflammatory injury.
Article
Chemistry, Multidisciplinary
Evren Gundogdu, Emine-Selin Demir, Meliha Ekinci, Emre Ozgenc, Derya Ilem-Ozdemir, Zeynep Senyigit, Isabel Gonzalez-Alvarez, Marival Bermejo
Summary: Imatinib-loaded nanostructured lipid carrier system (F16-IMT) was successfully developed and characterized in this study. The F16-IMT formulation exhibited small particle size, stability, and efficient drug release. It also showed good cellular uptake and cytotoxicity against CRL-1739 cells. These findings suggest that F16-IMT has the potential to be an effective treatment for GIST.
Article
Oncology
Alfonso Serrano Del Valle, Manuel Beltran-Visiedo, Victoria de Poo-Rodriguez, Nelia Jimenez-Alduan, Gemma Azaceta, Rosana Diez, Beatriz Martinez-Lazaro, Isabel Izquierdo, Luis Palomera, Javier Naval, Alberto Anel, Isabel Marzo
Summary: Immunogenic cell death (ICD) is an important process for antitumor immunosurveillance, characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP) such as calreticulin (CRT). In certain cancers, high levels of CRT have been found to be associated with improved immune surveillance and better patient prognosis. This study evaluated CRT levels in CD38(+) bone marrow mononuclear cells (BMMCs) of multiple myeloma (MM) patients and found that increased cell surface-CRT levels were associated with aggressive clinical features and worse prognosis in MM.
Article
Pharmacology & Pharmacy
Teresa Garcia-Martinez, Maria Dolores Belles-Medall, Maria Garcia-Cremades, Raul Ferrando-Piqueres, Victor Mangas-Sanjuan, Matilde Merino-Sanjuan
Summary: This study aimed to develop a population pharmacokinetic/pharmacodynamic model of daptomycin and establish optimal dose recommendations in patients with normal and impaired renal function. The results indicate that bactericidal effects for Gram+ strains can be achieved with specific daily doses based on body weight and renal function. By evaluating the impact of different dosing regimens on treatment outcomes, the study provides insights for optimizing the use of daptomycin.
Article
Chemistry, Multidisciplinary
Maria Gil-Moles, M. Elena Olmos, Miguel Monge, Manuel Beltran-Visiedo, Isabel Marzo, Jose M. Lopez-de-Luzuriaga, M. Concepcion Gimeno
Summary: Silver complexes with substituted terpyridine or tetra-2-pyridinylpyrazine ligands were synthesized and characterized. Despite the potential of combining metal properties and ligand's ability for DNA binding, studies on the anticancer properties of these silver complexes are limited. This study investigated the antiproliferative activity, stability, CT-DNA binding, and mechanism of cell death of these derivatives. The results showed high cytotoxicity against different tumor cells and a notable selectivity index between tumor cells and healthy lymphocytes T for certain compounds. The derivatives were found to moderately intercalate with CT-DNA and promote apoptosis through a mitochondrial pathway.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Cell Biology
Oscar Gonzalo, Andrea Benedi, Laura Vela, Alberto Anel, Javier Naval, Isabel Marzo
Summary: Evasion of apoptosis is a hallmark of cancer cells, which involves alterations in Bcl-2 family proteins. The BiFC technique was used to study interactions between different Bcl-2 family members in living cells, revealing a complex network of interactions. Differences in the regulation of Bax and Bak activation by antiapoptotic and BH3-only proteins were observed. Mutations lacking the BH3 domain did not affect the association between Bax and Bak, suggesting alternative surfaces of interaction.
Article
Pharmacology & Pharmacy
Barbara Sanchez-Dengra, Elena Garcia-Montoya, Isabel Gonzalez-Alvarez, Marival Bermejo, Marta Gonzalez-Alvarez
Summary: The aim of this study was to create and validate a new in vitro model capable of predicting the permeability across the blood-brain barrier in the presence of glioblastoma. The results showed that the co-culture model of MDCK and MDCK-MDR1 with U87-MG had high predictability in drug access to the central nervous system.
Article
Toxicology
Pablo Rodriguez-Belenguer, Eric March-Vila, Manuel Pastor, Victor Mangas-Sanjuan, Emilio Soria-Olivas
Summary: New Approach Methodologies (NAMs) have opened a new era in toxicology by aiming to replace animal testing. However, they still face complexities in terms of mechanism, chemical space, and methodology. To address these complexities, research has proposed the usage of combination predictive Quantitative Structure-Activity Relationship (QSAR) models, known as metamodels. Metamodels provide a more precise approach by focusing on different sub-mechanisms or subprocesses, consistently outperforming classical QSAR models.
TOXICOLOGY LETTERS
(2023)
Article
Biochemical Research Methods
Aymara Sancho-Araiz, Zinnia P. Parra-Guillen, Jean Bragard, Sergio Ardanza, Victor Mangas-Sanjuan, Inaki F. Troconiz
Summary: This article focuses on the mathematical modeling of unperturbed and perturbed tumor growth dynamics and aims to develop a data-driven semi-mechanistic model for describing non-monotonic tumor growth in untreated mice. The study also explores the use of the model to evaluate different drug scenarios in preclinical drug development.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Editorial Material
Pharmacology & Pharmacy
Maria Garcia-Cremades, Zinnia P. Parra-Guillen, Victor Mangas-Sanjuan, Hugo Geerts
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Barbara Sanchez-Dengra, Maria Alfonso, Isabel Gonzalez-Alvarez, Marival Bermejo, Marta Gonzalez-Alvarez, Ramon Martinez-Manez
Summary: The two types of nanoparticles loaded with ponatinib have been proven to be non-toxic to blood-brain barrier cells and have shown improved drug delivery to the brain compared to the free drug when administered intranasally. This research is significant for the treatment of brain cancer.