Article
Chemistry, Multidisciplinary
Janske Nel, David Siniscalco, Cecilia Hognon, Mathilde Bouche, Nadege Touche, Emilie Brunner, Philippe C. Gros, Antonio Monari, Stephanie Grandemange, Gregory Francius
Summary: This study characterized the effects of iron-based complexes on the structural and morphological properties of breast cell lines. The complexes caused cell softening, increased size, and subsequent re-stiffening. They also induced cytoskeletal and mitochondrial reorganization. Molecular dynamic simulation suggested direct internalization of the complexes and demonstrated that their effects were not solely due to physical interaction with the cell membrane.
Article
Biochemistry & Molecular Biology
Lucia M. Balsa, Luisina M. Solerno, Maria R. Rodriguez, Beatriz S. Parajon-Costa, Ana C. Gonzalez-Baro, Daniel F. Alonso, Juan Garona, Ignacio E. Leon
Summary: This study evaluated the antitumor activity of a copper compound in osteosarcoma cells and found that CuHL can inhibit cell proliferation and induce apoptosis. In addition, the in vivo experiment on mice also showed that CuHL has inhibitory effects on osteosarcoma. This study provides valuable reference for the development of new treatments for osteosarcoma.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Aleksandra M. Bondzic, Jelena J. Zakula, Lela B. Koricanac, Otilija D. Keta, Goran Janjic, Ivana S. Dordevic, Snezana U. Rajkovic
Summary: The stability, lipophilicity, in vitro cytotoxicity, and influence on acetylcholinesterase of five dinuclear platinum(II) complexes were evaluated. Some of the complexes showed promising anticancer activity and selectivity, with minimal effects on normal cells. Docking studies provided insights into the binding modes with acetylcholinesterase.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Medicinal
Hana Kostrhunova, Brondwyn S. McGhie, Lenka Markova, Olga Novakova, Jana Kasparkova, Janice R. Aldrich-Wright, Viktor Brabec
Summary: The platinum(II) complex Pt(II)56MeSS exhibits high potency against cancer cells but also displays side toxicity and in vivo activity. The synthesis of new platinum(IV) prodrugs combining Pt(II)56MeSS with diclofenac (DCF) is described. These Pt(IV) complexes show similar mechanisms of action as Pt(II)56MeSS and DCF, promoting antiproliferative activity and inducing cell death and immunogenic cell death in cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Kevin Morales, Sergi Rodriguez-Calado, Jordi Hernando, Julia Lorenzo, Antonio Rodriguez-Dieguez, Carlos Jaime, Pau Nolis, Merce Capdevila, Oscar Palacios, Marta Figueredo, Pau Bayon
Summary: This study presents the synthesis, characterization, photochemical properties, and cytotoxic activity of new semisquaraine-type Pt(II) complexes towards cisplatin-resistant cancer cell lines. The complexes showed promising photoactivatable properties, inducing a higher cytotoxic effect on tested cells compared to nonphotoactivated compounds. The mechanism of action of these complexes was studied, revealing a combined mode of action. The results suggest a therapeutically potential advantage of these photoactivated platinum complexes.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Hamid R. Shahsavari, Jiyun Hu, Samira Chamyani, Yoshie Sakamaki, Reza Babadi Aghakhanpour, Christopher Salmon, Masood Fereidoonnezhad, Ayyub Mojaddami, Parnian Peyvasteh, Hudson Beyzavi
Summary: Cationic cycloplatinated(II) complexes with bisphosphine ligands showed higher cytotoxicity compared to cisplatin across various cancer cell lines, especially complex 3 exhibiting excellent antiproliferative activity. The stability of these complexes in biological environments and their mode of interaction with DNA were also investigated.
Article
Chemistry, Inorganic & Nuclear
Rossella Caligiuri, Giuseppe Di Maio, Nicolas Godbert, Francesca Scarpelli, Angela Candreva, Isabella Rimoldi, Giorgio Facchetti, Maria Giovanna Lupo, Emilia Sicilia, Gloria Mazzone, Fortuna Ponte, Isabella Romeo, Massimo La Deda, Alessandra Crispini, Renata De Rose, Iolinda Aiello
Summary: A series of novel cationic curcumin-based Pt(II) complexes with neutral ligands and triflate anions have been synthesized and characterized. The antioxidant activity of these complexes was measured using DPPH and computational strategies were used to determine their mechanism of action. In addition, the growth inhibitory activity of the complexes against bacteria was tested using the disk diffusion technique.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Anup Paul, Priya Singh, Maxim L. Kuznetsov, Anirban Karmakar, M. Fatima C. Guedes da Silva, Biplob Koch, Armando J. L. Pombeiro
Summary: The two newly synthesized copper(II) compounds exhibit significant in vitro cytotoxic effects, particularly showing pronounced inhibitory effects on the proliferation of the breast cancer cell line MCF-7. Through various biological studies, the effective antiproliferative mechanism of compound 1 on breast cancer cells has been confirmed.
DALTON TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Angelico D. Aputen, Maria George Elias, Jayne Gilbert, Jennette A. Sakoff, Christopher P. Gordon, Kieran F. Scott, Janice R. Aldrich-Wright
Summary: The DNA-alkylating derivative chlorambucil was coordinated with atypical cytotoxic platinum(IV) complexes, resulting in prodrugs with remarkable antitumor potential. The prodrug 56CLB showed exceptionally high activity in multiple cancer cell lines and induced significant production of reactive oxygen species in treated cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Umut Dogan, Ozge Ozcan, Gizem Alaca, Aydan Ari, Salih Gunnaz, H. Tansel Yalcin, Onur Sahin, Sevil Irisli
Summary: Three new Platinum complexes were synthesized and characterized, showing moderate cytotoxic activities against cancer cell lines and antimicrobial effects on both gram positive and gram negative bacteria.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Inorganic & Nuclear
Pragti, Sreshtha Nayek, Satyam Singh, Avinash Sonawane, Ivo Grabchev, Rakesh Ganguly, Suman Mukhopadhyay
Summary: In this study, three Ru(II) arene complexes with a bidentate benzimidazole-based ligand were synthesized and their antitumor activity was studied by varying the co-ligand X. The synthesized compounds showed good interactions with serum albumin proteins, had good drug stability and lipophilic character. They were found to bind with DNA and could induce apoptosis in cancer cells, as well as upregulate cleaved caspase-3 expression and downregulate BCLXL expression. These findings provide a new direction for the investigation of antitumor ruthenium-based metallodrugs using benzimidazole-based ligands.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Stefano Scoditti, Gloria Mazzone, Nico Sanna, Emilia Sicilia
Summary: This study presents an in-depth computational investigation into the ability of a recently proposed multi-action Ru(II)-Pt(IV) conjugate to act as a photosensitizer in photodynamic therapy (PDT) and chemo-therapeutic drugs. The results show that the investigated complex is capable of releasing a light-absorbing chromophore for use in PDT, and it can also generate cytotoxic reactive oxygen species.
INORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kirill K. Geyl, Sergey V. Baykov, Stanislav A. Kalinin, Alexandr S. Bunev, Marina A. Troshina, Tatiana V. Sharonova, Mikhail Yu. Skripkin, Svetlana O. Kasatkina, Sofia I. Presnukhina, Anton A. Shetnev, Mikhail Yu. Krasavin, Vadim P. Boyarskiy
Summary: In this study, twelve previously unknown Cu(II) complexes were synthesized using a newly suggested protocol for conveniently accessing variously substituted 2-pyridyl ureas. The structures of the complexes were evaluated using elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two structural motifs were identified based on the substitution pattern on the 2-pyridine fragment. The antiproliferative activity of the synthesized complexes against lung cancer cell lines was investigated, along with their non-specific cytotoxicity against healthy cells. Certain complexes showed enhanced activity against drug-resistant cells with moderate selectivity towards normal cells. The mechanism of antiproliferative effect was studied through additional experiments, including cell cycle analysis and apoptosis induction test. The findings suggest that these 2-pyridyl urea-based Cu(II) complexes have potential as starting points for further exploration of their anticancer properties.
Article
Biochemistry & Molecular Biology
Zahra Shabaninejad, Maryam Nikkhah, S. Masoud Nabavizadeh
Summary: The DNA binding capacity and cytotoxic effects of two cycloplatinated complexes (C1 and C2) were evaluated. Both complexes exhibited high DNA binding affinity and were able to quench the fluorescence of ethidium bromide. They also induced DNA viscosity increase, confirming their intercalative interactions with DNA. C2 showed the highest cytotoxicity, particularly on a cisplatin resistant-cell line, and induced apoptosis comparable or higher than cisplatin in all cell lines.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Salah S. Massoud, Febee R. Louka, Madison T. Dial, Andrew J. Malek, Roland C. Fischer, Franz A. Mautner, Jan Vanco, Tomas Malina, Zdenek Dvorak, Zdenek Travnicek
Summary: A series of heteroleptic copper(II) complexes were synthesized and evaluated for their cytotoxicity. Complexes 1 and 2 showed the highest efficacy against human cancer cells, inducing apoptosis by increasing ROS production.
DALTON TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Monika Hreusova, Vojtech Novohradsky, Lenka Markova, Hana Kostrhunova, Ivan Potocnak, Viktor Brabec, Jana Kasparkova
Summary: In this study, a gallium(III) complex with cloxyquin ligands is found to effectively inhibit the proliferation of rhabdomyosarcoma cells, a type of aggressive and difficult-to-treat cancer in children. The complex exhibits selective toxicity towards cancer cells compared to noncancerous fibroblasts. It induces ferroptosis in rhabdomyosarcoma cells through interference with iron metabolism, and is capable of killing both bulk and stem cells. This is the first non-iron metal compound shown to induce ferroptosis in cancer cells.
BIOINORGANIC CHEMISTRY AND APPLICATIONS
(2022)
Article
Pharmacology & Pharmacy
Elise A. Schubert, Johannes C. Alffenaar, Masego T. Johnstone, John W. Barlow, Nial J. Wheate
Summary: This study found that certain concomitant medications and cannabis constituents may be associated with the incidence of adverse events when initiating medicinal cannabis.
INTERNATIONAL JOURNAL OF PHARMACY PRACTICE
(2023)
Article
Clinical Neurology
Elise A. Schubert, Masego T. Johnstone, Melissa J. Benson, Johannes C. Alffenaar, Nial J. Wheate
Summary: This study examined the tolerability and effectiveness of medicinal cannabis in patients with chronic, refractory pain, with a subset analysis on arthritis. The results showed that balanced CBD:THC products significantly reduced pain intensity scores, with 22% of patients experiencing a clinically meaningful reduction. Additionally, patients using CBD:THC balanced products showed improvements in various health-related quality of life outcomes.
BRITISH JOURNAL OF PAIN
(2023)
Article
Toxicology
Abrar Arbaeen, Firouzeh Noghrehchi, Nial J. Wheate, Rose Cairns
Summary: This study examines hospitalizations resulting from poisoning and envenomation in Australian children. It found that approximately 10 children are admitted to the hospital every day due to poisoning, with over 70% of cases being related to pharmaceuticals. The most common pharmaceutical poisoning involves non-opioid analgesics, antipyretics, and antirheumatics. Contact with venomous animals and toxic plants was the most common non-pharmaceutical exposure. Intensive care unit admission and deaths were rare.
CLINICAL TOXICOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Alba Hernandez-Garcia, Lenka Markova, Maria Dolores Santana, Jitka Pracharova, Delia Bautista, Hana Kostrhunova, Vojtech Novohradsky, Viktor Brabec, Jose Ruiz, Jana Kasparkova
Summary: This study presents the synthesis and characterization of six new heteroleptic osmium(II) complexes with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. These complexes are highly kinetically inert and absorb a full-wavelength range of visible light. The antiproliferative activity of these complexes has been investigated using human cancer and noncancerous cell cultures, showing that they are more potent than conventional cisplatin. The mechanism of action involves the activation of the endoplasmic reticulum stress pathway and disruption of calcium homeostasis.
INORGANIC CHEMISTRY
(2023)
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
Chemistry, Medicinal
Hana Kostrhunova, Brondwyn S. McGhie, Lenka Markova, Olga Novakova, Jana Kasparkova, Janice R. Aldrich-Wright, Viktor Brabec
Summary: The platinum(II) complex Pt(II)56MeSS exhibits high potency against cancer cells but also displays side toxicity and in vivo activity. The synthesis of new platinum(IV) prodrugs combining Pt(II)56MeSS with diclofenac (DCF) is described. These Pt(IV) complexes show similar mechanisms of action as Pt(II)56MeSS and DCF, promoting antiproliferative activity and inducing cell death and immunogenic cell death in cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jaroslav Malina, Hana Kostrhunova, Peter Scott, Viktor Brabec
Summary: Fe(II)-based metallohelices were found to stabilize various DNA junctions, with the highest selectivity for the Y-shaped 3WJ. These metallohelices were shown to efficiently kill cancer cells and induce DNA damage, offering potential therapeutic benefits.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Angelico D. Aputen, Maria George Elias, Jayne Gilbert, Jennette A. Sakoff, Christopher P. Gordon, Kieran F. Scott, Janice R. Aldrich-Wright
Summary: The development of new and versatile platinum(IV) complexes is a rapidly evolving research strategy for cancer drug discovery. In this study, platinum(IV) complexes conjugated with non-steroidal anti-inflammatory molecules were synthesized and showed significantly improved anti-tumor potential compared to traditional platinum(II) chemotherapy drugs. These complexes also demonstrated the ability to reduce cellular and mitochondrial activity, decrease cancer cell resistance to chemotherapy, and inhibit COX-2 enzyme, thereby reducing inflammation in cancer cells.
Article
Pharmacology & Pharmacy
Sophie K. Stack, Nial J. Wheate, Niamh C. Moloney, Sarah V. Abelev, John W. Barlow, Elise A. Schubert
Summary: This study evaluated the effectiveness and adverse events of using medicinal cannabis to treat anxiety disorders. The results showed that cannabis significantly improved anxiety, depression, fatigue, and social abilities. Common adverse events included dry mouth, somnolence, and fatigue, with THC associated with gastrointestinal discomfort.
JOURNAL OF PHARMACY TECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Amrita Sarkar, Vojtech Novohradsky, Moumita Maji, Tomer Babu, Lenka Markova, Hana Kostrhunova, Jana Kasparkova, Valentina Gandin, Viktor Brabec, Dan Gibson
Summary: A multitargeting prodrug (2) that releases gemcitabine, oxaliplatin, and doxorubicin in their active form in cancer cells is a potent cytotoxic agent. It selectively targets cancer cells with high selectivity indices and induces the release of DAMPs in CT26 cells. The prodrug also inhibits tumor growth in murine models with lower body weight loss compared to FDA drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Vojtech Novohradsky, Alicia Marco, Lenka Markova, Natalia Cutillas, Jose Ruiz, Viktor Brabec
Summary: In this study, a series of new octahedral iridium(III) complexes Ir1-Ir9 were reported, which showed potential for inhibiting metastasis in triple-negative breast cancer. The results demonstrated that the structural modifications within the complexes strongly influenced their anti-metastatic properties, with complex Ir1 exhibiting the highest activity. Contrary to the effects of the conventional chemotherapy drug doxorubicin, which promoted metastatic properties of TNBC cells, the results suggested that doxorubicin therapy may increase the risk of breast cancer metastasis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
J. P. C. Coverdale, H. Kostrhunova, L. Markova, H. Song, M. Postings, H. E. Bridgewater, V. Brabec, N. J. Rogers, P. Scott
Summary: Self-assembled enantiomers of a di-iron metallohelix showed different antiproliferative activities against HCT116 colon cancer cells, with the ?-helicity compound being more potent than the Delta compound. The accumulation and localization studies suggest that the ? enantiomer undergoes carrier-mediated efflux, while the Delta enantiomer undergoes equilibrative process. The binding of the ? metallohelix to DNA and inhibition of tubulin and actin networks contribute to its G(2)/M arrest effect on cells.
DALTON TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Jitka Pracharova, Hana Kostrhunova, Alessandra Barbanente, Nicola Margiotta, Viktor Brabec
Summary: This study confirms the excellent antiproliferative activity of the phosphaplatin derivative RRD2 in various cancer cell lines and analyzes its binding to nuclear DNA. The results demonstrate that DNA lesions caused by RRD2 contribute to killing cancer cells. Additionally, RRD2 accumulates in cancer cells to a lesser extent than cisplatin but exhibits similar binding efficiency to nuclear DNA after accumulation.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2023)