Screening of synthetic 1,2,3-triazolic compounds inspired by SRPIN340 as anti-Trypanosoma cruzi agents.

BACKGROUND: The current treatments for Chagas disease (CD) include benznidazole and nifurtimox, which have limited efficacy and cause numerous side effects. Triazoles are candidates for new CD treatments due to their ability to eliminate T. cruzi parasites by inhibiting ergosterol synthesis, thereby damaging the cell membranes of the parasite. METHODS: Eleven synthetic analogs of the kinase inhibitor SRPIN340 containing a triazole core (compounds 6A-6K) were screened in vitro against the Tulahuen strain transfected with ß-galactosidase, and their IC50, CC50, and selectivity indexes (SI) were calculated. Compounds with an SI > 50 were further evaluated in mice infected with the T. cruzi Y strain by rapid testing. RESULTS: Eight compounds were active in vitro with IC50 values ranging from 0.5-10.5 µg/mL. The most active compounds, 6E and 6H, had SI values of 125.2 and 69.6, respectively. These compounds also showed in vivo activity, leading to a reduction in parasitemia at doses of 10, 50, and 250 mg/kg/day. At doses of 50 and 250 mg/kg/day, parasitemia was significantly reduced compared to infected untreated animals, with no significant differences between the effects of 6E and 6H. CONCLUSIONS: This study identified two new promising compounds for CD chemotherapy and confirmed their activity against T. cruzi.

Drugs in preclinical and early clinical development for the treatment of Chagas´s disease: the current status.

INTRODUCTION: Chagas disease is spreading faster than expected in different countries, and little progress has been reported in the discovery of new drugs to combat Trypanosoma cruzi infection in humans. Recent clinical trials have ended with small hope. The pathophysiology of this neglected disease and the genetic diversity of parasites are exceptionally complex. The only two drugs available to treat patients are far from being safe, and their efficacy in the chronic phase is still unsatisfactory. AREAS COVERED: This review offers a comprehensive examination and critical review of data reported in the last 10 years, and it is focused on findings of clinical trials and data acquired in vivo in preclinical studies. EXPERT OPINION: The in vivo investigations classically in mice and dog models are also challenging and time-consuming to attest cure for infection. Poorly standardized protocols, availability of diagnosis methods and disease progression markers, the use of different T. cruzi strains with variable benznidazole sensitivities, and animals in different acute and chronic phases of infection contribute to it. More synchronized efforts between research groups in this field are required to put in evidence new promising substances, drug combinations, repurposing strategies, and new pharmaceutical formulations to impact the therapy.

Profile of wound healing process induced by allantoin / Perfil do processo de cicatrização induzido pela alantoína

PURPOSE: To evaluate and characterize the wound healing process profile induced by allantoin incorporated in soft lotion oil/water emulsion using the planimetric and histological methods. METHODS: Female Wistar rats (n=60) were randomly assigned to 3 experimental groups: (C) control group-without treatment; (E) group treated with soft lotion O/W emulsion excipients; (EA) group treated with soft lotion O/W emulsion containing allantoin 5 percent. The emulsions either containing or not allantoin were topically administered for 14 days and the wound area was evaluated by planimetry and by qualitative and quantitative histological analysis of open wound model. RESULTS: The data which were obtained and analyzed innovate by demonstrating, qualitatively and quantitatively, by histological analysis, the profile of healing process induced by allantoin. The results suggest that the wound healing mechanism induced by allantoin occurs via the regulation of inflammatory response and stimulus to fibroblastic proliferation and extracellular matrix synthesis. CONCLUSION: This work show, for the first time, the histological wound healing profile induced by allantoin in rats and demonstrated that it is able to ameliorate and fasten the reestablishment of the normal skin.

OBJETIVO: Avaliar e caracterizar o perfil cicatricial induzido pela alantoína incorporada em uma emulsão óleo/água, sob os aspectos planimétrico e histológico. MÉTODOS: Ratos Wistar fêmeas (n=60) foram agrupados aleatoriamente em três grupos experimentais grupo controle - sem tratamento (C); grupo tratado com emulsão pura (E); grupo tratado com emulsão contendo 5 por cento de alantoína (EA). As emulsões contendo ou não alantoína foram administradas topicamente durante 14 dias e a área da ferida foi avaliada por planimetria e por análise histológica qualitativa e quantitativa em modelo de ferida aberta. RESULTADOS: Na análise planimétrica não foi observado diferenças significativas entre os grupos experimentais. Os resultados da análise histológica sugerem que o mecanismo de cicatrização induzido pela alantoína ocorre via controle da resposta inflamatória e estímulos à proliferação fibroblástica e síntese de matrix extracelular de maneira mais intensa e rapidamente em relação aos grupos controles. CONCLUSÃO: Este trabalho mostra pela primeira vez o perfil histológico de cicatrização induzido pela alantoína em ratos, demonstrando ser capaz de melhorar e acelerar o processo de reconstituição da pele.

Nanotecnologia farmacêutica aplicada ao tratamento da malária: [revisão] / Application of pharmaceutical nanotechnology to the treatment of malaria: [review]

Apesar do desenvolvimento tecnológico e científico, a malária permanece como um dos maiores problemas de saúde a serem combatidos. As estratégias modernas para o controle da doença prevêem ações conjuntas, como o combate do inseto vetor, diagnóstico rápido e preciso, garantia de terapêutica adequada, redução dos casos de resistência, além do desenvolvimento de novos agentes terapêuticos e vacina e através da otimização da ação de fármacos utilizados na atualidade. Os sistemas de liberação controlada de fármacos vêm recebendo atenção especial nesta área de pesquisa, com o desenvolvimento de estratégias para a veiculação de agentes bioativos e vacinas na forma de nanodispositivos tais como lipossomas, nanopartículas e micropartículas. Diversos nanossistemas já demonstraram eficácia na otimização de vacinas e quimioterápicos destinados ao controle da malária. Este artigo de revisão tem por objetivo avaliar o estado da arte na terapêutica da malária e demonstrar o potencial da nanotecnologia farmacêutica como ferramenta destinada ao combate da doença.

In spite of living in a scientific and technological era, malaria continues to be one of the worldwide greatest health challenges. The state-of-the-art policy to keep malaria under control is expected to comprise joint-strategies, such as the vector control, fast diagnosis, therapeutic guarantee, resistance cutback, drug optimization and development of new therapeutic agents and vaccines. Nano and microcarrier systems have been receiving a special attention, including the development of strategies for carrying bioactive agents, vaccines through nanodevices, such as liposomes and nanoparticles, and microdevices, such as microparticles and microemulsions. Numerous nanosystems have already substantiated their effectiveness to optimize vaccines, insecticides, and chemotherapeutic agents applied to the control of malaria. This review is intended to explain the malaria scenario though the world, and to show the nanotechnology as a promising alternative for malaria control and treatment.