New ent-kaurene-type nor-diterpene and other compounds isolated from Annona vepretorum Mart. (Annonaceae).

A new nor-ent-kaurene diterpene and ten other compounds were isolated from Annona vepretorum stems, including four kaurene diterpenes, three alkamides, one sesquiterpene and two steroids. Their chemical structures were elucidated using spectroscopic methods, including 1D-, 2D-NMR, and HRESIMS. The absolute configuration of compounds 1, 5, 8, 9 and 10 was confirmed by CD experiments. Compounds 1-5 and 8-10 were evaluated for cytotoxic activity using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method, against three human carcinoma cell lines: human colon (HCT-116), glioblastoma (SF295) and prostate (PC3). However, all isolated compounds exhibited low cytotoxic activity.

Bis-nor-diterpene from Cnidoscolus quercifolius (Euphorbiaceae) induces tubulin depolymerization-mediated apoptosis in BRAF-mutated melanoma cells.

A phytochemical investigation of cytotoxic extract and fractions of Cnidoscolus quercifolius Pohl led to isolation of five terpenoids, including three lupane-type triterpenes (1-3) and two bis-nor-diterpenes (4-5). Compounds 4 (phyllacanthone) and 5 (favelanone) are commonly found in this species and have unique chemical structure. Although their cytotoxic activity against cancer cells has been previously reported, the anticancer potential of these molecules remains poorly explored. In this paper, the antimelanoma potential of phyllacanthone (PHY) was described for the first time. Cell viability assay showed a promising cytotoxic activity (IC50 = 40.9 µM) against chemoresistant human melanoma cells expressing the BRAF oncogenic mutation (A2058 cell line). After 72 h of treatment, PHY inhibited cell migration and induced apoptosis and cell cycle arrest (p < 0.05). Immunofluorescence assay showed that the pro-apoptotic effect of PHY is probably associated with tubulin depolymerization, resulting in cytoskeleton disruption of melanoma cells. Molecular docking investigation confirmed this hypothesis given that satisfactory interaction between PHY and tubulin was observed, particularly at the colchicine binding site. These results suggest PHY from C. quercifolius could be potential leader for the design of new antimelanoma drugs.

Drug associations as alternative and complementary therapy for neglected tropical diseases.

The present paper aims to establish different treatments for neglected tropical disease by a survey on drug conjugations and possible fixed-dose combinations (FDC) used to obtain alternative, safer and more effective treatments. The source databases used were Science Direct and PubMed/Medline, in the intervals between 2015 and 2021 with the drugs key-words or diseases, like "schistosomiasis", "praziquantel", "malaria", "artesunate", "Chagas' disease", "benznidazole", "filariasis", diethylcarbamazine", "ivermectin", " albendazole". 118 works were the object of intense analysis, other articles and documents were used to increase the quality of the studies, such as consensuses for harmonizing therapeutics and historical articles. As a result, an effective NTD control can be achieved when different public health approaches are combined with interventions guided by the epidemiology of each location and the availability of appropriate measures to detect, prevent and control disease. It was also possible to verify that the FDCs promote a simplification of the therapeutic regimen, which promotes better patient compliance and enables a reduction in the development of parasitic resistance, requiring further studies aimed at resistant strains, since the combined APIs usually act by different mechanisms or at different target sites. In addition to eliminating the process of developing a new drug based on the identification and validation of active compounds, which is a complex, long process and requires a strong long-term investment, other advantages that FDCs have are related to productive gain and gain from the industrial plant, which can favor and encourage the R&D of new FDCs not only for NTDs but also for other diseases that require the use of more than one drug.

Additive effect of the probiotics Lactobacillus exopolysaccharides and the Satureja calamintha extracts on enteropathogenic Escherichia coli adhesion

Abstract This study assessed the inhibitory potential of the probiotics Lactobacillus (LB) exopolysaccharides (EPS) with or without extracts of Satureja calamintha on enteropathogenic Escherichia coli (EPEc) responsible for gastroenteritis. Methanolic and hydromethanolic extracts were prepared by cold maceration and subjected to phytochemical screening. The compounds of the extracts were determined with the colorimetric assays and identified using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Antioxidant activities of the extracts were also evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging. Antibacterial effect on EPEc was evaluated by using both agar disc diffusion and microdilution methods. The in vitro test of auto-aggregation was investigated. Microbiological analysis showed that 63% of the isolated LB were producing EPS, with the amount ranging from 8.21 to 43.13 mg/L. Chemical analysis of the extracts revealed the presence of polyphenols and flavonoids, more abundant in the hydromethanolic extract, which presented the highest content with 2.11 mg EGA/g of polyphenol and 1.64 mg EC/g of flavonoids and 1.71 mg EGA/g of polyphenol and 1.15 mg EC/g of flavonoids in the methanolic extract. Hydromethanolic extracts and EPS exhibited a more important activity than did the methanolic extract against EPEc. The combined action of EPS and extracts reduced the aggregation ability of EPEc and decreased the rate of their adhesion.

Layered Double Hydroxides as Promising Excipients for Drug Delivery Purposes.

Layered Double Hydroxides (LDH) have received great attention in the development of drug carrier systems. LDHs have become intelligent excipients of high technological potential for the pharmaceutical industry due to their ability to intercalate biomaterials in the interlayer region, adsorb substances on its vast surface area, have flexible structure, swelling properties, high chemical and thermal stability, modulate drug release, have high biocompatibility and be easily synthesized. This article, using typical examples, mainly addresses the systems formed between LDHs and antimicrobial, antineoplastic and anti-inflammatory agents, which constitute the main pharmacological classes of wide interest due to the problems encountered with low solubility, control in administration, stability in body fluids and toxicity, among others. Additionally, the article also reports on the recent development of ternary or quaternary (multicomponent systems) compounds based on LDH, bringing the advantages of targeted therapy, improving the aqueous stability of nanohybrids and the performance of these inorganic carriers.

Metal organic frameworks (MOFs) with therapeutic and biomedical applications: a patent review.

Introduction: Metal organic frameworks (MOFs) are a recent group of nano porous materials with exceptional physical properties, such as large surface areas, high pore volumes, low densities and well-defined pores. This type of material has been used frequently for biomedical and therapeutic applications, such as drug delivery systems and theranostic materials.Areas covered: In this review, the authors searched for patents filed in the last 10 years, found in different databases, related to the therapeutic or biomedical application of MOFs for use in different health fields. The possibility of these new materials becoming new therapeutic possibilities available to the population was emphasized.Expert opinion: The advances in research with MOFs have grown in the last 10 years and with that many possibilities for their applications have emerged in several areas, especially biomedical. The possibility of using these materials in drug delivery systems is the most common form of possibility of use in the health area, mainly due to easy obtaining and high reproducibility, which are seen very positively by the drug development technology sector.

Beta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis.

ß-Lapachone is an ortho-naphthoquinone originally isolated from the heartwood of Handroanthus impetiginosus and can be obtained through synthesis from lapachol, naphthoquinones, and other aromatic compounds. ß-Lapachone is well known to inhibit topoisomerase I and to induce NAD(P)H: quinone oxidoreductase 1. Currently, phase II clinical trials are being conducted for the treatment of pancreatic cancer. In view of ever-increasing scientific interest in this naphthoquinone, herein, the authors present a review of the synthesis, physicochemical properties, biological activities, and toxicity of ß-lapachone. This natural compound has shown activity against several types of malignant tumors, such as lung and pancreatic cancers and melanoma. Furthermore, this ortho-naphthoquinone has antifungal and antibacterial activities, underscoring its action against resistant microorganisms and providing anti-inflammatory, antiobesity, antioxidant, neuroprotective, nephroprotective, and wound-healing properties. ß-Lapachone presents low toxicity, with no signs of toxicity against alveolar macrophages, dermal fibroblast cells, hepatocytes, or kidney cells.

Naphthoquinone-based Hydrazone Hybrids: Synthesis and Potent Activity Against Cancer Cell Lines.

BACKGROUND: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity. OBJECTIVE: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and ß- lapachones (α and ß, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. METHODS: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. RESULTS: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, compounds 3 and 4 being the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than ß-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90-12.40 µM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. CONCLUSION: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

Determination of phenolic compounds, in vitro antioxidant activity and characterization of secondary metabolites in different parts of Passiflora cincinnata by HPLC-DAD-MS/MS analysis.

Ethanol extracts of different parts of Passiflora cincinnata were obtained by maceration. The total phenolic and flavonoid contents were evaluated. The antioxidant activities were determined by ß-carotene-linoleic acid bleaching test, 2,2-diphenyl-1-picrylhydrazil (DPPH), and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging. The crude ethanol stem extract showed the highest amount of total polyphenols (45.53 mg gallic acid equivalent/g) while the highest total flavonoid contents (1.42 mg of quercetin equivalent/g) were observed in the leaf extract. The lowest IC50 (25.65 µg/ml) by the DPPH method was observed for the stem extract. The ABTS method showed a significant antioxidant activity for all investigated extracts. The secondary metabolite composition of ethanol extracts was assessed by HPLC-DAD-MS/MS analysis, leading to the identification of fourteen secondary metabolites in P. cincinnata extracts. These results showed the potentiality of this species as a source of phenolic compounds and antioxidants.

Spondias tuberosa inner bark extract exert antidiabetic effects in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus (DM) is one of the most important medical emergencies of the 21st century. However, commercially available oral drugs with antidiabetic properties have been limited because of potential side effects, such as: hypoglycemia, weight gain, hepatic dysfunction and abdominal discomfort. As well as antidiabetic drugs, many types of medicinal herbal supplements are utilized as alternative treatments for DM and related comorbidities. Spondias tuberosa Arruda (Anacardiaceae), popularly known as "umbu", has been used in traditional medicine to treat a vast range of diseases, including DM, infections, digestive disorders, diarrhea and menstrual abnormalities. AIM OF THE STUDY: This study evaluated the effect of the hydroethanolic extract of the inner stem bark of Spondias tuberosa (EEStb) in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced in rats by a single injection of STZ (40 mg/kg i.p.). Diabetic rats were treated with 250 mg/kg or 500 mg/kg of the EEStb for 21 days. Water intake, urinary volume, body weight, as well as biochemical parameters, such as cholesterol total (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), hepatic and muscle glycogen urea, alanine and aspartate aminotransferase, total protein, albumin, and glucose blood levels, were analyzed. We also determined the hepatic antioxidant state, as well as both of insulin and glucose tolerance. RESULTS: The extract was evaluated by HPLC, and the major components of EESTb were identified (i.e. gallic acid and quercetin). The 500 mg/kg dosage of EEStb significantly decreased fasting blood glucose and post-prandial glucose. The EEStb also reduced urinary volume, food and water intake, as well as decreased body weight gain. Diabetic rats that received EEStb had a lower loss of muscle mass and white adipose tissue. Additionally, EEStb improved the urinary excretion of urea and glucose. The extract significantly decreased triglycerides, total cholesterol and VLDL in diabetic rats. However, no significant effect was observed on the levels of total and HDL cholesterol. EEStb treatment prevented hepatotoxic diabetic-induced, improved GSH:GSSG ratio, SOD and CAT activity as well as reduced nitrite and TBARs levels. CONCLUSIONS: Our results demonstrate that EEStb has antioxidant and hepatoprotective effects as well as improves insulin sensibility in diabetic rats. This indicates that S. tuberosa could be a potential resource for alternative therapies in the treatment of hyperglycemic conditions. These results also support the use of EEStb in ethnomedicine for the management of diabetes.

Spondias purpurea L. (Anacardiaceae): Antioxidant and Antiulcer Activities of the Leaf Hexane Extract.

Spondias purpurea is used in folk medicine to treat diarrhea and diuresis. The objective of this study was to evaluate the phytochemical profile and antioxidant and antiulcer activities of the hexane extract of the leaves of S. purpurea (SpHE). Phytochemical profile was evaluated via thin layer chromatography (TLC) and HPLC. SpHE was screened for antioxidant activities using DPPH, ABTS, FRAP, and phosphomolybdenum assays. To determine its antiulcer properties, animals were pretreated with injured control, lansoprazole, ranitidine, carbenoxolone, or SpHE (12.5, 25, and 50 mg/kg) and were screened; acute ulcers were induced by HCl/ethanol, absolute ethanol, and nonsteroidal anti-inflammatory drug (NSAID). TLC revealed the presence of flavonoids, whereas HPLC analysis showed the presence of caffeic acid and epigallocatechin. The phenolic compounds and in vitro assays showed antioxidant activity. After gastric ulcer induction by using HCl/ethanol, SpHE reduced the area of ulcerative lesions by 82, 91, and 88%, respectively. In ethanol, SpHE reduced the area of ulcerative lesions by 77, 93, and 92%, respectively. In the NSAID, the percentages of protection were 70, 76, and 78%, respectively. SpHE promoted the minimization of ulcers, increased the levels of reduced glutathione, and decreased tumor necrosis factor. S. purpurea has antioxidant and antiulcer properties.

Schistosomiasis: Drugs used and treatment strategies.

Neglected tropical diseases (NTDs) affect millions of people in different geographic regions, especially the poorest and most vulnerable. Currently NTDs are prevalent in 149 countries, seventeen of these neglected tropical parasitic diseases are classified as endemic. One of the most important of these diseases is schistosomiasis, also known as bilharzia, a disease caused by the genus Schistosoma. It presents several species, such as Schistosoma haematobium, Schistosoma japonicum and Schistosoma mansoni, the latter being responsible for parasitosis in Brazil. Contamination occurs through exposure to contaminated water in the endemic region. This parasitosis is characterized by being initially asymptomatic, but it is able to evolve into more severe clinical forms, potentially causing death. Globally, more than 200 million people are infected with one of three Schistosome species, including an estimated 40 million women of reproductive age. In Brazil, about 12 million children require preventive chemotherapy with anthelmintic. However, according to the World Health Organization (WHO), only about 15% of the at-risk children receive regular treatment. The lack of investment by the pharmaceutical industry for the development and/or improvement of new pharmaceutical forms, mainly aimed at the pediatric public, is a great challenge. Currently, the main forms of treatment used for schistosomiasis are praziquantel (PZQ) and oxaminiquine (OXA). PZQ is the drug of choice because it presents as a high-spectrum anthelmintic, used in the treatment of all known species of schistosomiasis and some species of cestodes and trematodes. OXA, however, is not active against the three Schistosome species. This work presents a literature review regarding schistosomiasis. It addresses points such as available treatments, the role of the pharmaceutical industry against neglected diseases, and perspectives for treatment.

Estado da arte de Bauhinia forficata Link (Fabaceae) como alternativa terapêutica para o tratamento do diabetes melittus / Bauhinia forficata Link (Fabaceae) as alternativetherapy in the treatment of diabetes mellitus

O Diabetes mellitus, por tratar-se de uma doença crônica e por apresentar um crescimento acentuado na sociedade brasileira, tornou-se alvo da comunidade científica na busca de novas alternativas terapêuticas. Diversos estudos estão sendo desenvolvidos com o objetivo de comprovar as aparentes propriedades farmacológicas de espécies vegetais empregadas no tratamento desta enfermidade. Sendo assim, a Bauhinia forficata Link, comumente conhecida como pata-de-vaca, figura entre as espécies mais utilizadas para esse fim. Dentre os representantes de Bauhinia, a que apresenta maior número de estudos referentes à atividade hipoglicemiante e antidiabética é a espécie referida. Isto, pois, devido as suas atividades farmacológicas, diversos estudos relatam seus aspectos botânicos, composição química e eficácia. Esse constante interesse em seu estudo se mostra imperioso para sua utilização de forma segura e eficaz, possibilitando o desenvolvimento de formas farmacêuticas para o tratamento de diabetes.

Diabetes mellitus is a chronic disease with an ever-increasing incidence in Brazil and has become the object of scientific research into the search for novel therapeutic alternatives. A number of studies have been developed to demonstrate the pharmacological properties of plant species employed in folk medicine for the treatment of this disease. One such plant is the Brazilian white orchid tree, Bauhinia forficate Link, known locally as pata-de-vaca [cow foot]. Among representatives of the genus Bauhinia, this species has the greatest number of studies addressing its botanical aspects, chemical composition and effectiveness in terms of hypoglycemic and anti-diabetic activity. Studies on this plant are important to the safe, effective development of pharmaceutical products for the treatment of diabetes.

Caracterização físico-química do potencial agente antineoplásico Beta-lapachona / Physicochemical characterization of the anticancer drug Beta-lapachone

A Beta-lapachona tem inspirado uma série de trabalhos científicos, tendo em vista os inúmeros estudos farmacológicos relatados na literatura, que comprovam suas atividades antibacteriana, antifúngica, antitripanossômica, antiviral, anti-inflamatória e antineoplásica. Devido a sua potente atividade anticancerígena, este fármaco encontra-se, atualmente, em estudo clínico de fase II para o tratamento de câncer pancreático. O objetivo deste estudo foi determinar as propriedades físico-químicas deste ativo com o emprego de diversas ferramentas analíticas, como, difração de Raios X, infravermelho, análises térmicas, microscopia eletrônica de varredura e ensaio de dissolução. Os resultados obtidos na difração de raios X revelaram o padrão policristalino do fármaco; o infravermelho identificou os principais grupos funcionais da Beta-lapachona; os dados das análises térmicas apresentaram características de um produto cristalino e de alta pureza; a eletromicrografia demonstrou sua forma cristalina, como cristais acidulares bem definidos de tamanho regular, corroborando com os dados do difratograma. No estudo de dissolução comprovamos que a Beta-lapachona é praticamente insolúvel em água, sendo necessário o desenvolvimento de estratégias tecnológicas destinadas a melhorar a sua solubilidade em meio aquoso. Dessa forma, a determinação das principais características físico-químicas da Beta-lapachona será extremamente útil na identificação de problemas que possam vir a surgir durante a formulação e auxiliará no desenvolvimento de formas farmacêuticas mais eficazes e com qualidade.

A series of scientific papers on Beta-lapachone has been inspired by the numerous pharmacological reports in the literature that demonstrate its antibacterial, antifungal, antitrypanosomal, antiviral, anticancer and anti-inflammatory activities. Owing to its potent anticancer activity, this drug is currently undergoing phase II clinical trials for the treatment of pancreatic cancer. The aim of this study was to determine the physicochemical properties of this drug by means of several analytical tools, such as X-ray diffraction (XRD), infrared (IR) spectroscopy, thermal analysis, scanning electron microscopy (SEM) and dissolution test. The XRD patterns showed the polycrystalline state of the drug; IR spectroscopy identified the main functional groups of Beta-lapachone; the data from thermal analysis showed characteristics of a crystalline product of high purity and the SEM micrographs showed the crystalline form as well-defined acidulated crystals of regular size, corroborating the XRD patterns. In the dissolution test we found that Beta-lapachone is practically insoluble in water, necessitating the development of technological strategies to improve its solubility in aqueous media. Thus, the determination of the main physicochemical characteristics of Beta-lapachone will be extremely useful in identifying problems that may arise during the design and in the development of more effective and higher quality pharmaceutical forms of this drug.

Alternativas terapêuticas no combate à Esquistossomose Mansônica / Alternative therapeutic agents to combat Manson´s schistosomiasis

A esquistossomose mansônica é classificada pelo Ministério da Saúde como uma doença negligenciada, causada pelo trematódeo intravascular Schistosoma mansoni. As precárias condições de higiene estão diretamente relacionadas às áreas endêmicas, bem como à pobreza e ao baixo desenvolvimento econômico. Na atualidade, o praziquantel é o fármaco de escolha utilizado para o tratamento dessa patologia. No entanto, o mesmo é relativamente tóxico devido à sua baixa solubilidade, além de relatos acerca de parasitas resistentes ao tratamento. Nesse contexto, faz-se necessário buscar novas alternativas terapêuticas que possam ser utilizadas no tratamento dessa doença. Esta revisão trata da busca por uma nova quimioterapia e sugere a possibilidade de que formas mais adequadas de vetorização de medicamentos já existentes sejam capazes de associar vantagens terapêuticas ao fármaco de escolha para o tratamento proposto, de forma que a população infectada receba seus benefícios.

Manson´s schistosomiasis is classified by the Ministry of Health as a neglected disease caused by the intravascular trematode Schistosoma mansoni. Endemic areas are directly related to poor hygienic conditions, as well as poverty and a low level of economic development. Currently, praziquantel is the drug of choice used to treat this condition, but it is relatively toxic, due to its low solubility, and there are reports of the parasite developing resistance to the treatment. In this context, there is a need to search for new therapeutic agents that can be used to treat this disease. This review covers the search for a new chemotherapy and suggests the possibility that the best existing drug vectorization systems may be able to combine therapeutic advantages with the drug of choice for the treatment, to the benefit of the infected population.

Avanços, propriedades e aplicações de dispersões sólidas no desenvolvimento de formas farmacêuticas sólidas / Advances, properties and applications of solid dispersions in the development of solid dosage forms

Dispersões sólidas amorfas são amplamente utilizadas como estratégia na melhoria da biodisponibilidade de compostos pouco hidrossolúveis. Logo, a aplicação dessa técnica mostra-se como uma importante estratégia para as indústrias farmacêuticas, demonstrando também a necessidade do conhecimento aprofundado com relação às principais e mais recentes técnicas de obtenção utilizadas em escala laboratorial e industrial. Além das principais características físico-químicas dos polímeros hidrofílicos mais utilizados, relaciona suas vantagens e desvantagens, assim como as possibilidades de aplicação. Nesta revisão, pretende-se discutir os recentes avanços na área das dispersões sólidas e sua utilização em sistemas multicomponentes.

Amorphous solid dispersions feature widely in strategies to improve the bioavailability of poorly water-soluble compounds. However, there are few reports of this technique being used in finished products, demonstrating a need for in depth knowledge of the main and most recent production techniques used on the laboratory and industrial scale, as well as of the main physicochemical characteristics of the most widely used hydrophilic polymers, listing their advantages and disadvantages and potential applications. In this review, it is intended to discuss the recent advances regarding solid dispersions and their use in multicomponent systems.

Pesquisa, desenvolvimento e inovação para o controle das doenças negligenciadas / Research, development and innovation for the control of neglected diseases

O fluxo contínuo de novos produtos no mercado é fruto da inovação tecnológica apresentada pela Indústria Farmacêutica. O governo Brasileiro tem investido em iniciativas promissoras de inovação através do desenvolvimento de medicamentos para os programas públicos de saúde, instituindo o Programa de Pesquisa e Desenvolvimento em Doenças Negligenciadas, o qual foca sete doenças: dengue, doenças de Chagas, leishmaniose, hanseníase, malária, esquistossomose e tuberculose. O artigo foca uma revisão sobre P&D aplicada à prevenção e controle das doenças negligenciadas no Brasil e no mundo. Com base nos dados levantados, percebeu-se que são grandes as dificuldades para o desenvolvimento de P&D em tecnologias e produtos para combater as doenças negligenciadas e que são poucos os investimentos financeiros nesse segmento quando comparados aos de pesquisas que focam outras enfermidades. Diante disso, pode-se enfatizar a importância de investimentos em pesquisas nesse setor, em saneamento básico e programas educativos que orientem a população sobre combate à proliferação dos vetores e agentes causadores.

The steady stream of new products on the market is the result of technological innovation in the pharmaceutical industry. The Brazilian government has invested in promising initiatives for innovation through the development of drugs for public health programs, setting up the Program for Research and Development on Neglected Diseases, which focuses on seven diseases: dengue fever, Chagas? disease, leishmaniasis, Hansen?s disease, malaria, schistosomiasis and tuberculosis. The article reviews the R&D applied to the prevention and control of neglected diseases in Brazil and worldwide. On the basis of survey data, we note that there are great obstacles to the development of the technology and products needed to fight neglected diseases and there are few investments in this segment in comparison with research that focuses on other diseases. In this light, we stress the importance of investment in research in this area and in sanitation and educational programs to guide the population in combating the proliferation of vectors and causative agents.

Development and validation of a HPLC analytical assay method for efavirenz tablets: a medicine for HIV infections / Desenvolvimento e validação de um método de ensaio de HPLC analítica para comprimidos de efavirenz: um medicamento para infecções por HIV

Efavirenz is a reverse transcriptase non analog nucleoside inhibitor used to treat HIV infections. A simple assay method by high performance liquid chromatography was developed and validated for efavirenz tablets. The physical chemical characteristics of efavirenz were investigated to developing the method. The method was validated observing the parameters described in USP 29. Analyses were performed by an ultraviolet detector at a 252 nm wavelength, on a reverse-phase column (C18, 250 mm x 3.9 mm, 10 μm), using an isocratic mobile phase containing acetonitrile/water/orthophosphoric acid (70:30:0.1). The validation parameters used were: selectivity, linearity, precision, accuracy, robustness, detection and quantification limits, and all resulting data were treated by a statistical method. The results obtained confirmed an alternative assay method for efavirenz tablets adequate for routine industrial use.

O efavirenz é um inibidor não análogo de nucleosídeo da transcriptase reversa, utilizado no tratamento da infecção por HIV. Um método simples, por cromatografia líquida de alta eficiência, foi desenvolvido e validado para quantificação do efavirenz em comprimidos. O desenvolvimento do método levou em consideração as características físico-químicas do efavirenz. O método foi validado seguindo os parâmetros da USP 29. A análise foi realizada por meio de detector ultravioleta, utilizando um comprimento de onda de 252 nm, com coluna de fase reversa (C18, 250 mm x 3.9 mm, 10 μm) e fase móvel isocrática contendo acetonitrila/água/ácido ortofosfórico (70: 30: 0.1). Os critérios usados para validação foram: seletividade, linearidade, precisão, exatidão, robustez e limites de detecção e quantificação do método. Foi utilizado método estatístico em todas as etapas do processo de validação. Os resultados obtidos mostraram que o método é uma alternativa para quantificação do efavirenz em comprimidos, tornando viável seu uso na rotina industrial e laboratórios analíticos.