Article
Chemistry, Multidisciplinary
Mahendiran Dharmasivam, Busra Kaya, Tharushi P. Wijesinghe, Vera Richardson, Jeffrey R. Harmer, Miguel A. Gonzalvez, William Lewis, Mahan Gholam Azad, Paul V. Bernhardt, Des R. Richardson
Summary: This study investigates the synthesis and characterization of metal complexes of the Dp4e4mT analog, revealing their distinct effects and off-target activities in cancer treatment, with a key role played by differential transmetallation.
Article
Chemistry, Inorganic & Nuclear
Francesco Caruso, Gottumukkala Subbaraju, Modukuri Ramani, Marzia Gariboldi, Emanuela Marras, Carmen Kloer, Aron Sulovari, Sarjit Kaur, Miriam Rossi
Summary: This study synthesized three [(eta(6)-p-cymene)Ru(L)Cl] neutral complexes and evaluated their antiproliferative activity against lung cancer, colon cancer, and glioblastoma. The results showed that complexation significantly increased the antitumor activity of hispolon derivatives in glioblastoma, and the inhibitory ability towards aldehyde dehydrogenase was determined.
INORGANICA CHIMICA ACTA
(2022)
Article
Pharmacology & Pharmacy
Jakob Kljun, Renata Pavlic, Eva Hafner, Tanja Lipec, Sara Moreno-Da Silva, Primoz Tic, Iztok Turel, Tomaz Budefeld, Jure Stojan, Tea Lanisnik Rizner
Summary: This study presents the synthesis and kinetic studies of organoruthenium compounds with different ligands and their inhibitory activity towards AKR1C enzymes. It also examines their potential as anticancer agents for chemoresistant ovarian cancer. Results show that these compounds are potent inhibitors of AKR enzymes and exhibit a unique inhibitory mechanism. Additionally, they demonstrate moderate yet better anti-proliferative and anti-migration effects on chemoresistant ovarian cancer cells.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ran Tao, Yin Lu, Wubing Xia, Changwei Zhang, Chengzhang Wang
Summary: This study successfully prepared a ruthenium coordination polymer composite with chitosan quaternary ammonium polymers and shikimic acid. The composite showed good antibacterial properties, with a strong inhibitory effect against S. aureus and the ability to disrupt their biofilm formation. Further mechanism studies revealed that the composite influenced the cell membrane integrity and intracellular Ca2+ levels of S. aureus.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Multidisciplinary Sciences
Asmaa M. Fahim, Sawsan Dacrory, Ghada H. Elsayed
Summary: In this study, microcrystalline cellulose was oxidized to cellulose aldehyde using NaIO4 under microwave irradiation. The resulting cellulose aldehyde was further reacted with uracil acetamide to yield arylidene cellulose MDAU(4), which can react with nitrogen nucleophiles and cyclize to form pyrazole cellulose MDPA(5). The obtained cellulosic derivatives were characterized using FT-IR, NMR, and SEM. Cytotoxic activity analysis showed that compound MDAU(4) exhibited stronger inhibitory effect on the growth of A549 and Caco2 cancer cells compared to standard values. The expression levels of Wnt signaling cascade genes in A549 cells were also investigated and compound MDAU(4) was found to reduce the expression levels of these genes. Docking simulation was used to study the binding of uracil cellulosic heterocycles to different proteins.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Inorganic & Nuclear
Urszula K. Komarnicka, Sandra Koziel, Agnieszka Skorska-Stania, Agnieszka Kyziol, Francesco Tisato
Summary: In this study, new complexes based on ruthenium(II) and iridium(III) with phosphine ligands and phenyl rings with/without methoxy motifs were synthesized and characterized. The complexes showed high catalytic efficiency in the oxidation of NADH to NAD(+) and exhibited potential applications in biological and medical fields. Furthermore, they demonstrated redox activity and significant cytotoxicity against various cancer cell lines.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Dana Josa, David Aguila, Pere Fontova, Vanessa Soto-Cerrato, Piedad Herrera-Ramirez, Laia Rafols, Arnald Grabulosa, Patrick Gamez
Summary: Five metal-arene complexes and nine cyclometalated half-sandwich complexes were synthesized, characterized, and evaluated for cytotoxicity against human cancer cells. The complexes showed notable cytotoxic properties, particularly against lung adenocarcinoma cells. One of the complexes also exhibited significant toxic effects on other cell lines. Furthermore, the study identified a complex that impacted the cell cycle of lung adenocarcinoma cells.
DALTON TRANSACTIONS
(2023)
Article
Multidisciplinary Sciences
James McNulty, Chanti Babu-Dokuburra, Jon Scattolon, Carlos Zepeda-Velazquez, Maribeth A. Wesesky, Jill K. Caldwell, Wenxiao Zheng, Jadranka Milosevic, Paul R. Kinchington, David C. Bloom, Vishwajit L. Nimgaonkar, Leonardo D'Aiuto
Summary: The total synthesis of four novel mono-methoxy and hydroxyl substituted ring-A dihydronarciclasine derivatives identified the 7-hydroxyl derivative as a potent and selective antiviral agent against SARSCoV-2 and HSV-1. The IC50 for inhibiting HSV-1 infection, determined using induced pluripotent stem cells-derived brain organ organoids, was estimated to be 0.504 μM and 0.209 μM. No significant reduction in organoid viability was observed up to concentrations of 50 mM. Genomic expression analyses revealed activation of host-cell innate immunity, including the integrated stress response and type I IFN, as factors enhancing host-defense mechanisms against viral infection. In vivo experiments showed that the compound significantly reduced HSV-1 shedding in mouse eyes.
SCIENTIFIC REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Feng-Wei Guo, Qun Zhang, Yu-Cheng Gu, Chang-Lun Shao
Summary: In this paper, we reviewed 95 new sulfur-containing marine natural products isolated between 2021 and March 2023. We also discussed the strategies and emerging technologies, such as natural product-based antibody drug conjugates (ADCs), small-molecule-based proteolysis targeting chimeras (PROTACs), nanotechnology-based drug carriers, and artificial intelligence-driven drug discovery, that have been used to improve the efficiency and success rate of NP-based drug development. Additionally, we provided perspectives on the challenges, opportunities, and future research directions in sulfur-containing marine natural product-based drug discovery and development.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Review
Engineering, Chemical
Fredrik Lehmann, Johan Wennerberg
Summary: Despite significant advancements in anticancer drug development, there is a critical need for novel agents with unique but effective mechanisms to combat highly aggressive and drug-resistant tumors. Alkylating agents, particularly nitrogen-based ones, are commonly used for hematological and solid malignancies, exerting their antineoplastic effects throughout the cell cycle. Certain alkylating agents have been designed to enhance penetration into cells and increase their activity against tumors.
Article
Biochemistry & Molecular Biology
Rabina Pradhan, Laxmi Tiwari, Vincent M. Groner, Caleb Leach, Kyle Lusk, Nathan S. Harrison, Kenneth A. Cornell, Kristopher Waynant
Summary: Redox-active azothioformamides (ATFs) containing NNCS 1,3-heterodiene motif were synthesized and tested. The ATF compounds showed little antimicrobial activity alone, but exhibited cytotoxicity against lung carcinoma cells and leukemia cells. When coordinated with copper(I) and silver(I), the ATFs showed antimicrobial activity and cytotoxicity against fungi and cancer cells.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Xiangwen Liao, Lianghong Liu, Yanhui Tan, Guijuan Jiang, Haihong Fang, Yanshi Xiong, Xuemin Duan, Guangbin Jiang, Jintao Wang
Summary: Novel ruthenium complexes functionalized with benzothiophene exhibited good antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, with Ru(II)-3 showing the highest activity. Additionally, Ru(II)-3 demonstrated synergism with aminoglycoside antibiotics and potentially inhibited the regulatory function of SaCcpA. In vivo studies in a murine skin infection model further supported the antimicrobial efficacy of these complexes.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Multidisciplinary
Srividya Swaminathan, Jebiti Haribabu, Naveen Kumar Kalagatur, Maroli Nikhil, Nithya Balakrishnan, Nattamai S. P. Bhuvanesh, Krishna Kadirvelu, Ponmalai Kolandaivel, Ramasamy Karvembu
Summary: The synthesis of fourteen new Ru-II-arene complexes were characterized and found to exhibit high toxicity towards IMR-32 cancer cells, with two complexes showing the highest activity and the ability to induce apoptosis and cell cycle arrest. These complexes also demonstrated good binding affinity with receptors commonly overexpressed in cancer cells.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Hai-Yan Huang, Qian Wang, Chun-Yan Zhang, Zi-Xiang Chen, Jin-Tao Wang, Xiang-Wen Liao, Ru-Jian Yu, Yan-Shi Xiong
Summary: In this study, four ruthenium complexes modified with selenium-ether were synthesized and showed excellent antibacterial activity against Staphylococcus aureus (S. aureus). The most active complex, Ru(II)-4, efficiently targeted the bacterial cell membrane, preventing drug resistance and inhibiting biofilm formation. In toxicity experiments, Ru(II)-4 exhibited low mammalian toxicity. In vivo tests using both G. mellonella wax worms and mouse skin infection models confirmed the potential of Ru(II)-4 as an effective antibacterial agent against S. aureus infections, with minimal toxicity to mouse tissue. These findings highlight the promising strategy of introducing selenium-atom into ruthenium compounds for developing interesting antibacterial agents.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Review
Oncology
Sabyasachi Banerjee, Subhasis Banerjee
Summary: Metal-based therapy, especially platinum complexes, has become a significant approach in treating cancer. Advances in the understanding of biomolecular mechanisms have led to the development of non-classical platinum-based complexes with different mechanisms of action. The synthesis of new metal-based complexes with improved cytotoxicity and safety profiles has also been a focus. Several agents are currently in clinical trials or awaiting regulatory approval.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2022)
Article
Environmental Sciences
Yao Chen, Gerardino D. Errico, Massimiliano Fabbricino, Noemi Gallucci, Ludovico Pontoni, Marco Race, Sicong Yao
Summary: This study investigates the interaction between organic nanoparticles (ON) and various dyes in aqueous solution. The results show that there is a strong dynamic interaction between dye molecules and ON aggregates. The dye molecules are found to bind to the functional groups of ON through H-bonds, and are sequestrated into the hydrophobic core of ON aggregates. Nuclear magnetic resonance and electron paramagnetic resonance analysis confirm the formation of supramolecular aggregates with stable micellar hydrophobic structure.
ENVIRONMENTAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Ester Colarusso, Sara Ceccacci, Maria Chiara Monti, Erica Gazzillo, Assunta Giordano, Maria Giovanna Chini, Maria Grazia Ferraro, Marialuisa Piccolo, Dafne Ruggiero, Carlo Irace, Stefania Terracciano, Ines Bruno, Giuseppe Bifulco, Gianluigi Lauro
Summary: Targeting bromodomain-containing protein 9 (BRD9), a set of 2,4,5-trisubstituted-2,4-dihydro-3H- 1,2,4-triazol-3-one-based compounds was investigated for the development of new anticancer agents. Through in silico studies, chemical synthesis, biophysical and biological evaluation, compounds with promising selectivity and binding affinity for BRD9 were identified. The multidisciplinary approach used in this study accelerated the selection process and provided insights for the synthesis of novel BRD9 binders.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Marco Campanile, Rosario Oliva, Gerardino D'Errico, Pompea Del Vecchio, Luigi Petraccone
Summary: LL-III is an anticancer peptide that can translocate across tumor cell membranes. However, the mechanism through which it enters the cell cytoplasm is still unknown. In this study, we used physico-chemical techniques to characterize the interaction of LL-III with liposomes resembling the lipid matrix of the tumor cell membrane. Our results show that the peptide selectively interacts with the model tumor cell membrane without disrupting the lipid bilayer, but alters its properties by promoting lipid reorganization and increasing membrane permeability.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Maria Grazia Ferraro, Marco Bocchetti, Claudia Riccardi, Marco Trifuoggi, Luigi Paduano, Daniela Montesarchio, Gabriella Misso, Rita Santamaria, Marialuisa Piccolo, Carlo Irace
Summary: Based on strong preclinical evidence, this study focuses on the treatment of challenging indications, such as TNBC, using a novel ruthenium-based metallotherapeutics. An experimental model was used to validate the potential of the liposomal nanoformulation HoThyRu/DOTAP, which effectively delivered the antiproliferative compound AziRu to inhibit TNBC cell growth, migration, and invasion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chiara Platella, Andrea Criscuolo, Claudia Riccardi, Rosa Gaglione, Angela Arciello, Domenica Musumeci, Marina DellaGreca, Daniela Montesarchio
Summary: Despite their well-known and various bioactivities, in-depth studies on the interaction of natural compounds with cancer-related G-quadruplex structures have only recently been undertaken. In this study, a mini-library of phenanthrenoid analogues was investigated for their selective recognition of G-quadruplexes. Compounds 3 and 6 emerged as the most selective and active ligands, targeting the grooves/flanking residues of G-quadruplex structures. These compounds showed a preference for the hybrid telomeric G-quadruplex and exhibited anticancer activity in human cancer cells. Overall, these compounds are promising starting scaffolds for the design of analogues with high and selective anticancer activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chiara Platella, Francesca Ghirga, Domenica Musumeci, Deborah Quaglio, Pasquale Zizza, Sara Iachettini, Carmen D'Angelo, Annamaria Biroccio, Bruno Botta, Mattia Mori, Daniela Montesarchio
Summary: In this study, five natural compounds were investigated as analogs of promising G-quadruplex-targeting ligands to identify highly effective and selective anticancer candidates. Among them, Dicentrine was found to be the most effective ligand for telomeric and oncogenic G-quadruplexes, showing good selectivity. In-depth studies demonstrated that Dicentrine thermally stabilizes G-quadruplexes without affecting the control duplex, with higher affinity for G-quadruplex structures. Molecular dynamics simulations indicated that Dicentrine preferentially binds the G-quadruplex groove or the outer G-tetrad. Biological assays confirmed that Dicentrine promotes potent and selective anticancer activity by inducing cell cycle arrest through apoptosis, targeting G-quadruplex structures at telomeres.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Rodolfo Esposito, Immacolata Speciale, Cristina De Castro, Gerardino D'Errico, Irene Russo Krauss
Summary: To protect human and environmental health, researchers are focusing on discovering and developing new molecules with high biocompatibility and biodegradability. Surfactants are particularly urgent in this matter, and biosurfactants derived from microorganisms are a promising alternative. Rhamnolipids, a well-known family of biosurfactants, have been extensively studied for their production and physicochemical characterization, although a clear structure-function relationship is still lacking. This review aims to provide a comprehensive discussion of the physicochemical properties of rhamnolipids under different solution conditions and their structure, while also addressing unresolved issues for their potential replacement of conventional surfactants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rita Argenziano, Maria Laura Alfieri, Noemi Gallucci, Gerardino D'Errico, Lucia Panzella, Alessandra Napolitano
Summary: The search for new synthetic melanin-related pigments with antioxidant and photoprotective properties is important for dermo-cosmetic purposes. In this study, a melanin derived from 5,6-dihydroxyindole-2-carboxylic acid (DHICA) was synthesized and found to have similar structural properties to DHICA melanin. The synthesized pigment demonstrated stronger UV-visible absorption and improved solubility compared to DHICA melanin. Furthermore, the pigment exhibited marked antioxidant properties and enhanced inhibitory action against lipid peroxidation. These findings suggest that the melanin derived from DHICA has potential as a functional ingredient in dermo-cosmetic formulations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Claudia Riccardi, Antonella Campanella, Daniela Montesarchio, Pompea Del Vecchio, Rosario Oliva, Luigi Paduano
Summary: Ruthenium(III) complexes show promise as metal-based anticancer drugs. This study investigates the interaction of a Ru(III) complex embedded in a liposomal nanosystem with human serum proteins HSA and hTf, using fluorescence spectroscopy and circular dichroism. The results suggest that the nanosystem can interact with the serum proteins without affecting their secondary structures.
Article
Chemistry, Multidisciplinary
Flaviana Di Lorenzo, Simone Nicolardi, Roberta Marchetti, Adele Vanacore, Noemi Gallucci, Katarzyna Duda, Ferran Nieto Fabregat, Ha Ngoc Anh Nguyen, Djamel Gully, James Saenz, Eric Giraud, Luigi Paduano, Antonio Molinaro, Gerardino D'Errico, Alba Silipo
Summary: The ability of Methylobacterium extorquens to grow on methanol as the sole carbon and energy source is influenced by the composition and function of the lipopolysaccharide (LPS) in the outer membrane. The LPS of M. extorquens is unique, with non-phosphorylated and heavily O-methylated core oligosaccharides, and a distinctive lipid A structure. These chemical features impact the resistance of the membrane to methanol, regulating membrane ordering and dynamics.
Editorial Material
Biochemistry & Molecular Biology
Montserrat Terrazas, Ramon Eritja, Daniela Montesarchio
Article
Biochemistry & Molecular Biology
Claudia Riccardi, Chiara Platella, Domenica Musumeci, Daniela Montesarchio
Summary: Recently, we have focused on the preparation of nucleolipid-based Ru(III) complexes that can form supramolecular aggregates under physiological conditions. These complexes can prevent metal deactivation and efficiently deliver Ru(III) into cells for its therapeutic activity.
Article
Engineering, Environmental
Virginia Venezia, Mariavittoria Verrillo, Noemi Gallucci, Rocco Di Girolamo, Giuseppina Luciani, Gerardino D'Errico, Luigi Paduano, Alessandro Piccolo, Giuseppe Vitiello
Summary: The waste-to-wealth strategy promotes the design of new value-added materials using biowastes. Humic Acids (HA) are intriguing due to their supramolecular associations, which enable adsorption, chelation, redox behavior, and antibacterial activity. Combining HA with semiconductor nanoparticles allows for the creation of nanostructured hybrids with advanced properties. The study provides insights into producing low-cost organo-inorganic nanomaterials with redox and biocide properties to address environmental and health issues.
JOURNAL OF ENVIRONMENTAL CHEMICAL ENGINEERING
(2023)
Article
Engineering, Biomedical
Lin-Lin Luo, Jie Xu, Bing-Qiao Wang, Chen Chen, Xi Chen, Qiu-Mei Hu, Yu-Qiu Wang, Wan-Yun Zhang, Wan-Xiang Jiang, Xin-Ting Li, Hu Zhou, Xiao Xiao, Kai Zhao, Sen Lin
Summary: A novel AAV serotype, AAVYC5, introduced in this study, showed more efficient transduction into multiple retinal layers compared to AAV2, and enabled successful delivery of anti-angiogenic molecules in mice and non-human primates.
