RESUMO
Ruthenium complexes currently represent a perspective subject of investigation in terms of potential anticancer therapeutics. Eight novel octahedral ruthenium(II) complexes are the subject of this article. Complexes contain 2,2'-bipyridine molecules and salicylates as ligands, differing in position and type of halogen substituent. The structure of the complexes was determined via X-ray structural analysis and NMR spectroscopy. All complexes were characterized by spectral methods-FTIR, UV-Vis, ESI-MS. Complexes show sufficient stability in solutions. Therefore, their biological properties were studied. Binding ability to BSA, interaction with DNA, as well as in vitro antiproliferative effects against MCF-7 and U-118MG cell lines were investigated. Several complexes showed anticancer effects against these cell lines.
Assuntos
Antineoplásicos , Complexos de Coordenação , Compostos Heterocíclicos , Rutênio , Rutênio/farmacologia , Rutênio/química , Halogênios , Ligação Proteica , Complexos de Coordenação/química , Antineoplásicos/química , Linhagem Celular TumoralRESUMO
Life is chiral, as its constituents consist, to a large degree, of optically active molecules, be they macromolecules (proteins, nucleic acids) or small biomolecules. Hence, these molecules interact disparately with different enantiomers of chiral compounds, creating a preference for a particular enantiomer. This chiral discrimination is of special importance in medicinal chemistry, since many pharmacologically active compounds are used as racemates-equimolar mixtures of two enantiomers. Each of these enantiomers may express different behaviour in terms of pharmacodynamics, pharmacokinetics, and toxicity. The application of only one enantiomer may improve the bioactivity of a drug, as well as reduce the incidence and intensity of adverse effects. This is of special significance regarding the structure of natural products since the great majority of these compounds contain one or several chiral centres. In the present survey, we discuss the impact of chirality on anticancer chemotherapy and highlight the recent developments in this area. Particular attention has been given to synthetic derivatives of drugs of natural origin, as naturally occurring compounds constitute a major pool of new pharmacological leads. Studies have been selected which report the differential activity of the enantiomers or the activities of a single enantiomer and the racemate.
Assuntos
Química Farmacêutica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , EstereoisomerismoRESUMO
So far, the polyphenolic components of turmeric have shown a significant pharmacological preventative activity for a wide spectrum of diseases, including oncological disorders. This type of natural product could be of great interest for the inhibition of cancer cell proliferation, displaying less side effects in comparison to classical chemotherapeutics. The poor bioavailability and quick metabolism of such natural compounds require new investigative methods to improve their stability in the organisms. A synthetic approach to increase the efficiency of curcuminoids is to coordinate them to metals through the beta-dicarbonyl moiety. We report the synthesis and the biological attempts on human ovarian carcinoma A2780 of ruthenium(II) complexes 1-4, containing curcuminoid ligands. The cytotoxicity of complexes 1-4 proves their antiproliferative capability, and a correlation between the IC50 values and NF-κB transcription factor, FGF-2, and MMP-9 levels was figured out through the principal component analysis (PCA).
Assuntos
Antineoplásicos , Curcumina , Neoplasias Ovarianas , Rutênio , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Curcumina/uso terapêutico , Diarileptanoides , Feminino , Fator 2 de Crescimento de Fibroblastos , Humanos , Ligantes , Metaloproteinase 9 da Matriz , Neoplasias Ovarianas/tratamento farmacológico , Rutênio/farmacologiaRESUMO
Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal-ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.
Assuntos
Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação , Citotoxinas , DNA de Neoplasias , Diarileptanoides , Simulação de Acoplamento Molecular , Paládio , Células 3T3 , Animais , Células CACO-2 , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Citotoxinas/química , Citotoxinas/farmacologia , DNA de Neoplasias/química , DNA de Neoplasias/metabolismo , Diarileptanoides/química , Diarileptanoides/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Células HeLa , Humanos , Células Jurkat , Células MCF-7 , Camundongos , Paládio/química , Paládio/farmacologiaRESUMO
Bioactive metal complexes represent a promising and rapidly evolving area of pharmacotherapy. After the first part of our survey on metallopharmaceuticals dealing with antimicrobial activity of metal complexes and their application in diagnostics and the second part dedicated to anticancer properties of these compounds, this third and last part of the review focuses on several other applications of metals in therapy (mainly on the therapy of rheumatoid arthritis, some mental diseases, diabetes, as well as on chelation therapy). Following a brief account of the historical development of clinical use of the respective category of drugs, their chemical properties, toxicity, clinical applications and mechanism of action are discussed. The aim of this brief survey is to provide basic outline of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public.
Assuntos
Complexos de Coordenação/farmacologia , Medicina/tendências , Farmácia/tendências , Metais/farmacologiaRESUMO
Therapy of malignant tumors is among the oldest and at the same time the most promising application areas of therapeutic metal complexes. The second part of our survey on metallopharmaceuticals deals with historical development and current state of coordination compounds in cancer therapy. It starts with the most famous and most successful metallodrug - cisplatin. After a brief account of the discovery of the anticancer properties of this substance follows the discussion of its chemical properties, toxicity, clinical application and resistance. Hereafter, complexes of other metals along with innovative research directions are addressed. The aim of this brief survey is to provide basic overview of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public.
Assuntos
Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Metais/uso terapêutico , Neoplasias/tratamento farmacológico , HumanosRESUMO
The aim of this study was to analyze the binding interactions between a common antihypertensive drug (amlodipine besylate-AML) and the widely distributed plant flavonoid quercetin (Q), in the presence of human serum albumin (HSA). Fluorescence analysis was implemented to investigate the effect of ligands on albumin intrinsic fluorescence and to define the binding and quenching properties. Further methods, such as circular dichroism and FT-IR, were used to obtain more details. The data show that both of these compounds bind to Sudlow's Site 1 on HSA and that there exists a competitive interaction between them. Q is able to displace AML from its binding site and the presence of AML makes it easier for Q to bind. AML binds with the lower affinity and if the binding site is already occupied by Q, it binds to the secondary binding site inside the same hydrophobic pocket of Sudlow's Site 1, with exactly the same affinity. Experimental data were complemented with molecular docking studies. The obtained results provide useful information about possible pharmacokinetic interactions upon simultaneous co-administration of the food/dietary supplement and the antihypertensive drug.
Assuntos
Anlodipino/química , Relação Quantitativa Estrutura-Atividade , Quercetina/química , Albumina Sérica Humana/química , Anlodipino/metabolismo , Anlodipino/farmacocinética , Interações Medicamentosas , Humanos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Quercetina/metabolismo , Quercetina/farmacocinética , Albumina Sérica Humana/metabolismo , Análise EspectralRESUMO
Biologically active Knoevenagel condensates (1-14) of diarylheptanoids: 1,7-bis(3-methoxy-4-hydroxyphenyl)hepta-1,7-diene-3,5-dione and 1,7-bis(3-ethoxy-4-hydroxyphenyl)hepta-1,7-diene-3,5-dione, were synthesized and structurally characterized. Compounds 1-14 exhibited cytotoxicity against colon carcinoma cells, and their antiproliferative effect was associated with a significant decrease of multidrug resistance proteins. One of the underlying mechanisms of these effects is the reduction of intracellular and extracellular SOD enzymes by compounds 1, 12 and 14, which render the tumor cells more vulnerable to oxidative stress.
Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/patologia , Diarileptanoides/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Diarileptanoides/química , Humanos , Superóxido Dismutase/metabolismoRESUMO
A series of dialkylamino and nitrogen heterocyclic analogues of hexadecylphosphocholine and cetyltrimethylammonium bromide have been synthesized. The prepared compounds exhibit significant cytotoxic, antifungal and antiprotozoal activities. Alkylphosphocholines possess higher antifungal activity against Candida albicans in comparison with quaternary ammonium compounds. However, quaternary ammonium compounds exhibit significant higher activity against human tumor cells and Acanthamoeba lugdunensis compared to alkylphosphocholines. In addition, their haemolytic toxicity has been investigated. The relationship between structure and biological activity of the tested compounds is discussed.