Biological Activities of Bismuth Compounds: An Overview of the New Findings and the Old Challenges Not Yet Overcome.

Bismuth-based drugs have been used primarily to treat ulcers caused by Helicobacter pylori and other gastrointestinal ailments. Combined with antibiotics, these drugs also possess synergistic activity, making them ideal for multiple therapy regimens and overcoming bacterial resistance. Compounds based on bismuth have a low cost, are safe for human use, and some of them are also effective against tumoral cells, leishmaniasis, fungi, and viruses. However, these compounds have limited bioavailability in physiological environments. As a result, there is a growing interest in developing new bismuth compounds and approaches to overcome this challenge. Considering the beneficial properties of bismuth and the importance of discovering new drugs, this review focused on the last decade's updates involving bismuth compounds, especially those with potent activity and low toxicity, desirable characteristics for developing new drugs. In addition, bismuth-based compounds with dual activity were also highlighted, as well as their modes of action and structure-activity relationship, among other relevant discoveries. In this way, we hope this review provides a fertile ground for rationalizing new bismuth-based drugs.

Synthesis, characterization and cytotoxicity of copper (II) complex containing a 2H-benzo[e][1,3]oxazin derivative.

A new cis-dihalo copper(II) complex, [CuII(HLbz)(Cl)2].CH3CN (1), where HLbz = (S)-2-(((2-(2-(pyridin-2-yl)-2H-benzo[e][1,3]oxazin-3(4H)-yl)ethyl)amino)methyl)phenol), was isolated by reacting copper(II) chloride dihydrate and the H2L ligand (H2L = 2,2'-((2-(pyridin-2-yl)imidazolidine-1,3-diyl)bis(methylene))diphenol) in a MeOH/CH3CN (1:3 v/v) mixture. The complex formation occurred via the ligand modification during complexation, producing a unique structure containing 2H-benzo[e][1,3]oxazin, as observed from the single crystal X-ray structure determination. The complex was characterized by elemental analysis, potentiometric titration, spectroscopic techniques (UV-Vis, FT-IR) and conductance measurements. Complex 1 inhibits the growth of myelogenous leukemia cells with an IC50 of 17.3 µmol L-1.

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements.

Nanotechnology-based approaches for targeting the delivery and controlled release of metal-based therapeutic agents have revealed significant potential as tools for enhancing the therapeutic effect of metal-based agents and minimizing their systemic toxicities. In this context, a series of polymer-based nanosized systems designed to physically load or covalently conjugate metal-based therapeutic agents have been remarkably improving their bioavailability and anticancer efficacy. Initially, the polymeric nanocarriers were applied for platinum-based chemotherapeutic agents resulting in some nanoformulations currently in clinical tests and even in medical applications. At present, these nanoassemblies have been slowly expanding for nonplatinum-containing metal-based chemotherapeutic agents. Interestingly, for metal-based photosensitizers (PS) applied in photodynamic therapy (PDT), especially for cancer treatment, strategies employing polymeric nanocarriers have been investigated for almost 30 years. In this review, we address the polymeric nanocarrier-assisted metal-based therapeutics agent delivery systems with a specific focus on non-platinum systems; we explore some biological and physicochemical aspects of the polymer-metallodrug assembly. Finally, we summarize some recent advances in polymeric nanosystems coupled with metal-based compounds that present potential for successful clinical applications as chemotherapeutic or photosensitizing agents. We hope this review can provide a fertile ground for the innovative design of polymeric nanosystems for targeting the delivery and controlled release of metal-containing therapeutic agents.

Photocytotoxic Activity of Ruthenium(II) Complexes with Phenanthroline-Hydrazone Ligands.

This paper reports on the synthesis and characterization of two new polypyridyl-hydrazone Schiff bases, (E)-N'-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)thiophene-2-carbohydrazide (L1) and (E)-N'-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)furan-2-carbohydrazide (L2), and their two Ru(II) complexes of the general formula [RuCl(DMSO)(phen)(Ln)](PF6). Considering that hydrazides are a structural part of severa l drugs and metal complexes containing phenanthroline derivatives are known to interact with DNA and to exhibit antitumor activity, more potent anticancer agents can be obtained by covalently linking the thiophene acid hydrazide or the furoic acid hydrazide to a 1,10-phenanthroline moiety. These ligands and the Ru(II) complexes were characterized by elemental analyses, electronic, vibrational, 1H NMR, and ESI-MS spectroscopies. Ru is bound to two different N-heterocyclic ligands. One chloride and one S-bonded DMSO in cis-configuration to each other complete the octahedral coordination sphere around the metal ion. The ligands are very effective in inhibiting cellular growth in a chronic myelogenous leukemia cell line, K562. Both complexes are able to interact with DNA and present moderate cytotoxic activity, but 5 min of UV-light exposure increases cytotoxicity by three times.

New AlIIIZnII and AlIIICuII dinuclear complexes: Phosphatase-like activity and cytotoxicity.

Herein, we report the synthesis and characterization of the first two AlIII(µ-OH)MII (M = Zn (1) and Cu (2)) complexes with the unsymmetrical ligand H2L{2-[[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl]-6-bis(pyridylmethyl)aminomethyl}-4-methylphenol. The complexes were characterized through elemental analysis, X-ray crystallography, IR spectroscopy, mass spectrometry and potentiometric titration. In addition, complex 2 was characterized by electronic spectroscopy. Kinetics studies on the hydrolysis of the model substrate bis(2,4-dinitrophenyl)phosphate by 1 and 2 show Michaelis-Menten behavior, with 1 being slightly more active (8.31%) than 2 (at pH 7.0). The antimicrobial effect of the compounds was studied using four bacterial strains (Staphylococcus aureus, Pseudomonas aeuruginosa, Shigella sonnei and Shigella dysenteriae) and for both complexes the inhibition of bacterial growth was superior to that caused by sulfapyridine, but inferior to that of tetracycline. The dark cytotoxicity and photocytotoxicity (under UV-A light) of the complexes in a chronic myelogenous leukemia cell line were investigated. Complexes 1 and 2 exhibited significant cytotoxic activity against K562 cells, which undergoes a 2-fold increase on applying 5 min of irradiation with UV-A light. Complex 2 was more effective and a good correlation between cytotoxicity and intracellular concentration was observed, the intracellular copper concentration required to inhibit 50% of cell growth being 3.5 × 10-15 mol cell-1.

In vitro and in vivo antitumoral activity of a ternary copper (II) complex.

Recently, a high number of copper derivatives has been evaluated as DNA-targeting metallodrugs, due to the lower toxicity and its potential to cleave DNA. Several strategies have been testing to develop metal compounds effective against tumour cells. In this work, the ternary copper (doxycycline)-(1,10-phenanthroline) complex [Cu(dox)(phen)]2+ was especially designed as an antitumoral drug, previously showing high cytotoxicity and DNA cleavage activity. We aimed to further investigate the in vitro cytotoxic activity in both tumoral and non-tumoral cells, in vitro genotoxic potential, and in vivo antitumor activity using BALB/C mouse injected with sarcoma S180 and Ehrlich cell lines. Our results indicated that this compound exhibits a moderate genotoxic potential, with selective growth inhibition of tumor cells, especially the murine melanoma B16F10. Its main mechanism of action seems to be through ROS generation. We have further shown a significant reduction of the implanted tumor size in the animal model, suggesting that this compound has great antitumoral potential against many tumor types. [Cu(dox)(phen)]2+ is selectively cytotoxic for melanoma B16F10 and showed high chemotherapeutic potential in vivo against implanted sarcoma S180 and Ehrlich ascites tumours.

Concomitant and controlled release of furazolidone and bismuth(III) incorporated in a cross-linked sodium alginate-carboxymethyl cellulose hydrogel.

The combination of bismuth(III) citrate and the antibiotic furazolidone (FDZ) results in a synergetic effect on Helicobacter pylori eradication. However, the problems associated with their oral administration are challenges to overcome. Thus, in the present study, sodium alginate (SA)/carboxymethyl cellulose (CMC) blend hydrogels (SC) were developed for concomitant and controlled release of furazolidone and bismuth(III). The blank formulation (SCblank) and the three drug-loaded hydrogels (SCFDZ, SCBi, and SCFDZ-Bi) were prepared by casting method and characterized by infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, and X ray powder diffraction analyses. The swelling equilibrium and cumulative release amounts of FDZ and Bi3+ have indicated distinct behaviors of the hydrogels to different pH values. The bismuth-containing sample (SCFDZ-Bi) presents more resistance to degradation on a neutral solution and shows more suitable properties for controlled drug release than the sample without bismuth (SCFDZ). Microbiological studies, using Escherichia coli as a model, show bacteria viability reduction in presence of the drug-loaded samples. The developed system containing furazolidone and bismuth(III) appears to be promising for oral administration with concomitant and controlled release of these drugs aimed at the pharmacological treatment of gastrointestinal disorders.

Sexual function, anxiety and depression in women with benign breast disease. A case-control study.

INTRODUCTION: Sexual dysfunction is highly prevalent, affecting 40% of the female population. The incidence of such dysfunction is known to be higher among women with malignant breast disease and in patients with depression or anxiety. However, there are few data regarding the prevalence of sexual dysfunction among women with benign breast disease (BBD). OBJECTIVE: To evaluate the incidence of sexual dysfunction, depression and anxiety among women with BBD, in comparison with that observed for healthy women. METHOD: We evaluated the incidence of sexual dysfunction in 60 patients with benign breast disease (fibroadenomas, breast cysts, breast pain and phyllodes tumor) and 69 healthy women (control group). Participants completed the Sexual Quotient Questionnaire for Females (SQQ-F), the Beck Depression Inventory and the Beck Anxiety Inventory. Statistical analysis revealed that depression and anxiety were comparable between BBD and control groups (10.3 vs. 20.3% and 38.7 vs. 34.3%, respectively, p>0.05). The mean SQQ-F score (65.6±22.7 vs. 70.1±16.8; p>0.05) and sexual dysfunction (33.3 vs. 25.4%; p=0.324) were similar between BBD and control groups. CONCLUSION: We found no differences between women with BBD and healthy women in terms of the incidence of sexual dysfunction, anxiety and depression. Nevertheless, given the high prevalence of this condition, it is important to assess sexual quality of life, as well as overall quality of life, in women with BBD.

Sexual function, anxiety and depression in women with benign breast disease. A case-control study / Disfunção sexual, ansiedade e depressão em mulheres com câncer de mama benigno. Um estudo de caso-controle

Summary Introduction: Sexual dysfunction is highly prevalent, affecting 40% of the female population. The incidence of such dysfunction is known to be higher among women with malignant breast disease and in patients with depression or anxiety. However, there are few data regarding the prevalence of sexual dysfunction among women with benign breast disease (BBD). Objective: To evaluate the incidence of sexual dysfunction, depression and anxiety among women with BBD, in comparison with that observed for healthy women. Method: We evaluated the incidence of sexual dysfunction in 60 patients with benign breast disease (fibroadenomas, breast cysts, breast pain and phyllodes tumor) and 69 healthy women (control group). Participants completed the Sexual Quotient Questionnaire for Females (SQQ-F), the Beck Depression Inventory and the Beck Anxiety Inventory. Statistical analysis revealed that depression and anxiety were comparable between BBD and control groups (10.3 vs. 20.3% and 38.7 vs. 34.3%, respectively, p>0.05). The mean SQQ-F score (65.6±22.7 vs. 70.1±16.8; p>0.05) and sexual dysfunction (33.3 vs. 25.4%; p=0.324) were similar between BBD and control groups. Conclusion: We found no differences between women with BBD and healthy women in terms of the incidence of sexual dysfunction, anxiety and depression. Nevertheless, given the high prevalence of this condition, it is important to assess sexual quality of life, as well as overall quality of life, in women with BBD.

Resumo Introdução: A disfunção sexual é altamente prevalente, afetando 40% da população feminina. A incidência de tal disfunção é conhecida por ser maior entre as mulheres com câncer de mama e pacientes com ansiedade e depressão. No entanto, existem poucos dados sobre a prevalência de disfunção sexual entre mulheres com doença benigna da mama (BBD). Objetivo: Avaliar a incidência de disfunção sexual, depressão e ansiedade em mulheres com BBD, em comparação a mulheres saudáveis. Método: Avaliamos a incidência de disfunção sexual em 60 pacientes com doença benigna da mama (fibroadenomas, cistos mamários, dor mamária e tumor phyllodes) e 69 mulheres saudáveis (grupo controle). As participantes completaram o Questionário de Quociente Sexual para Mulheres (SQQ-F), o Inventário de Depressão de Beck e o Inventário de Ansiedade de Beck. A análise estatística revelou que a depressão e a ansiedade eram comparáveis entre os grupos BBD e controle (10,3 vs. 20,3% e 38,7 vs. 34,3%, respectivamente, p>0,05). O escore médio de SQQ-F (65,6±22,7 vs. 70,1±16,8; p>0,05) e a disfunção sexual (33,3 vs. 25,4%; p=0,324) foram semelhantes entre os grupos BBD e controle. Conclusão: Não encontramos diferenças entre mulheres com BBD e mulheres saudáveis em termos de incidência de disfunção sexual, ansiedade e depressão. No entanto, dada a alta prevalência dessa condição, é importante avaliar a qualidade de vida sexual, bem como a qualidade de vida global, em mulheres com BBD.

Avaliação do perfil nutricional dos pacientes internados na oncologia pediátrica do Hospital Santa Casa de Misericórdia De Belo Horizonte - MG / Nutritional assessment profile of hospitalized patients in oncology pediatric of Santa Casa de Misericordia Hospital, Belo Horizonte - MG

O câncer infantojuvenil é definido como toda neoplasia maligna que acomete indivíduos de até 19 anos de idade. Os sinais de má nutrição nas crianças e nos adolescentes com câncer são frequentes e os efeitos do tratamento agressivo aumentam ainda mais as chances de comprometimento nutricional. O objetivo deste estudo foi avaliar o estado nutricional dos pacientes internados na oncologia pediátrica do Hospital Santa Casa de Misericórdia de Belo Horizonte ­ MG. O estudo é do tipo descritivo, prospectivo e de natureza exploratória. A amostra contou com 32 pacientes de ambos os sexos, menores de 19 anos internados no período de janeiro a março de 2015. A coleta de dados foi feita através de prontuários e dados antropométricos contidos no sistema "Àgeis Nutrition - DeNutri".A maioria dos pacientes avaliados foi do sexo masculino e o tipo de neoplasia mais frequente foi leucemia. Segundo a classificação gerada pelas curvas da WHO, 50% (n=10) dos pacientes com tumores hematológicos e 41,7% (n=5) dos pacientes com tumores sólidos apresentavam-se eutróficos. Já o percentual de adequação da CB mostrou, que, mesmo estando classificados como eutróficos pela avaliação antropométrica, estes pacientes apresentaram algum grau de desnutrição. A eutrofia foi o diagnóstico nutricional mais frequente, mas a presença de baixo peso entre estes pacientes deve servir de alerta para uma intervenção nutricional precoce e individualizada a fim de corrigir os déficits nutricionais e evitar complicações ao quadro clínico.