Tuning the Cytotoxicity of Bis-Phosphino-Amines Ruthenium(II) Para-Cymene Complexes for Clinical Development in Breast Cancer

Despite some limitations such as long-term side effects or the potential presence of intrinsic or acquired resistance, platinum compounds are key therapeutic components for the treatment of several solid tumors. To overcome these limitations, maintaining the same efficacy, organometallic ruthenium(II) compounds have been proposed as a viable alternative to platinum agents as they have a more favorable toxicity profile and represent an ideal template for both, high-throughput and rational drug design. To support the preclinical development of bis-phoshino-amine ruthenium compounds in the treatment of breast cancer, we carried out chemical modifications in the structure of these derivatives with the aim of designing less toxic and more efficient therapeutic agents. We report new bis-phoshino-amine ligands and the synthesis of their ruthenium counterparts. The novel ligands and compounds were fully characterized, water stability analyzed, and their in vitro cytotoxicity against a panel of tumor cell lines representative of different breast cancer subtypes was evaluated. The mechanism of action of the lead compound of the series was explored. In vivo toxicity was also assessed. The results obtained in this article might pave the way for the clinical development of these compounds in breast cancer therapy.

Coordination Chemistry of Ruthenium

Ruthenium is one of the rare elements that belongs to the platinum group metals. Ruthenium is very effective hardener for platinum and palladium. Well studied coordination and organometallic chemistry of ruthenium results in a various varieties of compounds. There are various features of ruthenium such as oxidation states, coordination numbers and geometries. Ruthenium compounds have various applications and also have low toxicity and they are ideal for the catalytic synthesis of drugs. The field of ruthenium chemistry is very broad and is extremely diverse in the field of catalysis and medicinal chemistry. This review article shows a classical general chemistry of ruthenium compounds.

Ruthenium(II) and Platinum(II) Complexes with Biologically Active Aminoflavone Ligands Exhibit In Vitro Anticancer Activity

Continuing our studies on the mechanisms underlying the cytotoxicity of potential drugs, we have described several aspects of the in vitro anticancer activity of ruthenium(II) and platinum(II) complexes with bioactive, synthetic aminoflavone ligands. We examined the mechanism of proapoptotic activity of cis-dichlorobis(3-imino-2-methoxyflavanone)ruthenium(II), cis-dichlorobis(3-imino-2-ethoxyflavanone)ruthenium(II), and trans-dichlorobis(3-aminoflavone)platinum(II). Cisplatin was used as a reference compound. The cytotoxicity was investigated by MTT assay. The mechanism of proapoptotic activity of the tested compounds was investigated by evaluation of caspase-8 activity, cytometric analysis of annexin-V positive cells, and mitochondrial potential loss measurement. The results showed that ruthenium compounds break partially or completely the cisplatin resistance by activating the caspase 8-dependent apoptosis pathway and loss of mitochondrial membrane potential. Platinum compounds also have a cytostatic effect, but their action requires more exposure time. Potential mechanisms underlying drug resistance in the two pairs of cancer cell lines were investigated: total glutathione content, P-glycoprotein activity, and differences in the activity of DNA repair induced by nucleotide excision. Results showed that cisplatin-resistant cells have elevated glutathione levels relative to sensitive cells. Moreover, they indicated the mechanisms enabling cells to avoid apoptosis caused by DNA damage. Pg-P activity has no effect on the development of cisplatin resistance in the cell lines described.

Ruthenium based antifungal compounds and their activity

Ruthenium is recognized as a highly attractive alternative to platinum since the toxicity of many ruthenium compounds is lower and some complexes are quite selective for antifungal drugs. Ruthenium has various chemical properties these chemical properties are very useful for antifungal drug design. Ruthenium compounds have several types of advantages as antifungal drugs because of lower toxicity. . Ruthenium has unique properties making it of particularly use as fungal in drug design specially in antifungal drugs. Several types of ruthenium complexes and their antifungal activity standards are described here.

Photoinduced DNA Cleavage and Photocytotoxic of Phenanthroline-Based Ligand Ruthenium Compounds

The photophysical and biological properties of two new phenanthroline-based ligand ruthenium complexes were investigated in detail. Their DNA interaction modes were determined to be the intercalation mode using spectra titration and viscosity measurements. Under irradiation, obvious photo-reduced DNA cleavages were observed in the two complexes via singlet oxygen generation. Furthermore, complex 2 showed higher DNA affinity, photocleavage activity, and singlet oxygen quantum yields than complex 1. The two complexes showed no toxicity towards tumor cells (HeLa, A549, and A375) in the dark. However, obvious photocytotoxicities were observed in the two complexes. Complex 2 exhibited large PIs (phototherapeutic indices) (ca. 400) towards HeLa cells. The study suggests that these complexes may act as DNA intercalators, DNA photocleavers, and photocytotoxic agents.

Cytotoxic evaluation and DNA interaction of RuII-bipy complexes containing coumarin-based ligands

Despite the various treatment options for cancer, this disease still has caused increasing number of deaths, demanding more efficient, selective and less harmful drugs. Several class of ruthenium compounds have...

Proceedings - CBIOS Science Sessions 2020

Science Sessions 2020 Catarina Rosado and L Monteiro Rodrigues, eds. Vinicius Cuña, Universidade Lusófona de Humanidades e Tecnologias `````````````````````````````````` p.2 Oxygen Ozone Therapy - Tool in Veterinary Medicine Oxigênio Ozônio Terapia - Ferramenta na Medicina Veterinária Elisabete Silva, Faculdade de Ciências da Universidade de Lisboa p.2 Eco-friendly mon-biocide-releasing antifouling coatings for biofouling prevention Revestimentos antivegetativos monocidas amigos do ambiente para a prevenção de biofouling Amélia Pilar Rauter, Centro de Química Estrutural, Faculdade de Ciências; Universidade de Lisboa, p.3 Departamento de Química e Bioquímica, CiênciasULisboa. The sustainable chemistry of sugars: New antibacterial with a new mechanism of action A química sustentável dos açúcares: Novos antibacterianos com um novo mecanismo de ação Sofia Ramos, CBIOS Lusófona’s Research Center for Biosciences and Health Technologies p.4 Expression profile of cellular redox and calcium signaling-related genes: role in breast cancer progression Perfil de expressão de genes redox celulares e de sinalização de cálcio: papel na progressão do cancro da mama Ana Coutinho, Departamento de Química e Bioquímica. Faculdade de Ciências da Universidade de Lisboa p.4 Studying the conformational plasticity of KcsA potassium channel by homo-FRET Estudo da plasticidade conformacional do canal de potássio KcsA por homo-FRET Andreia Valente, Centro de Química Estrutural da Faculdade de Ciências da Universidade de Lisboa` p.5 Targeted cancer therapy using ruthenium compounds Terapia específica do cancro usando compostos de ruténio Sérgio Faloni Andrade, CBIOS Lusófona’s Research Center for Biosciences and Health Technologies p.5 Natural products and their potential to treat gastrointestinal inflammatory and ulcerative diseases Produtos naturais e o seu potencial para tratar doenças inflamatórias e ulcerativas gastrointestinais Cláudia Nunes, LAQV, Requimte, FFUP p.6 Fat nanoparticles: a diet towards targeted nano delivery Nanopartículas de gordura: uma dieta orientada para a nanodeficiência Cíntia Ferreira-Pêgo, CBIOS Lusófona’s Research Center for Biosciences and Health Technologies p.6 Mediterranean diet adherence, eating behavior and body shape concerns in Portuguese university students Adesão à dieta mediterrânica, comportamento alimentar e preocupações com a forma do corpo em estudantes universitários portugueses João Gregório, CBIOS Lusófona's Research Center for Biosciences and Health Technologies p. 7 "Pharmacists' guide to the future: challenges and opportunities for research and development of pharmacy services" "Guia dos farmacêuticos para o futuro: desafios e oportunidades para a investigação e desenvolvimento dos serviços de farmácia" Andreia Valença, Universidade Lusófona de Humanidades e Tecnologias p. 7 TIM2: a new membrane receiver for ferritin-H in the retina of murganho TIM2: um novo receptor de membrana para a ferritina-H na retina de murganho