Anti-Sporothrix brasiliensis activity of different pyrazinoic acid prodrugs: a repurposing evaluation

From drug repurposing studies, this work aimed to evaluate the activity of different pyrazinoic acid (POA) derivatives against Sporothrix brasiliensis. The POA esters were prepared and characterized as previously reported by classical esterification reactions, with good to excellent yields. Sporothrix brasiliensis isolates from cats (n=6) and standard strains of S. brasiliensis and S. schenckii were used to assess the antifungal activity of the POA derivatives through broth microdilution assay (CLSI M38-A2). Among the tested compounds, molecules 3 and 4 showed fungistatic and fungicidal activities against all Sporothrix spp. strains, and the obtained MIC and MFC values ranged from 2.12 to 4.24 mg/mL and from 1.29 to 5.15 mg/mL, respectively. Compound 2 and 5 were active as in vitro inhibitors of fungal growth, but showed weak fungicidal activity, while molecules 1 and POA itself were inactive. The results suggest the activity of POA derivatives against Sporothrix spp. may be dependent on the lipophilicity. In addition, the antifungal susceptibility of the isolates to itraconazole was performed, showing that two Sporothrix isolates from cats were itraconazole-resistant. Compounds 3 and 4 were also active against these itraconazole-resistant isolates, indicating a possible alternative route to the standard mode of action of itraconazole.

Planejamento e sintese de compostos potencialmente ligantes dos receptores 5-HT2C e H4 / Design and synthesis of compounds potentially ligands of 5-HT2C e H4

A serotonina e a histamina são duas das mais importantes aminas biogênicas do organismo. Regulam série de funções fisiológicas, como fluxo sanguíneo, temperatura corpórea, sono, fome, liberação de hormônios, comportamento afetivo e humor, entre outras. Assim, há grande interesse no planejamento e desenvolvimento de fármacos que interferem na transmissão serotoninérgica e histaminérgica, para futura aplicação como antidepressivos, antipsicóticos, ansiolíticos e anorexígenos, além de perifericamente, apresentarem possíveis ações antiinflamatórias. O objetivo deste trabalho é apresentar a síntese de compostos contendo os núcleos pirrolquinolínico, benzoindólico e benzodiidrofurânico com potencial atividade ligante nos receptores 5-HT2C e H4, assim como avaliar a seletividade desses compostos em comparação aos receptores 5-HT2A/B e H3. Sintetizou-se série de compostos utilizando reações de alilação, adição à carbonila, termociclização, rearranjo de Claisen, iodociclização e substituição nucleofílica para a obtenção dos compostos finais. Estudos de otimização de síntese por metodologia de superfície de resposta também são apresentados, assim como estudos de relações quantitativas entre estrutura química e atividade biológica de compostos ligantes dos receptores 5-HT2C e H4

Serotonin and histamine are two major biogenic amines in the body. They regulate several physiological functions such as blood flow, body temperature, sleep, hunger, hormone release, emotional behavior and mood, among others. Thus, there is great interest in the design and development of drugs that interfere with serotoninergic and histaminergic transmission, for future use as antidepressants, antipsychotics, anxiolytics and anorectic, and peripherally, possible anti-inflammatory actions. The aim of this work is to present the synthesis of compounds containing the pyrroloquinoline, benzoindole and benzodihydrofurane nucleus with potential binding activity to 5-HT2C and H4 receptors, as well as to evaluate the selectivity of these compounds in comparison to 5-HT2A/B and H3. Series of compounds were synthesized using allylation, carbonyl addition, thermal cyclization, Claisen rearrangement, iodocyclization and nucleophilic substitution reactions. Optimization studies for the synthesis using response surface methodology are also presented, as well as quantitative structure-activity relationships studies of ligands of 5-HT2C and H4 receptors

Prevalência de disfuncões crânio cervicais em pacientes portadores de disfunções temporomandibulares / Prevalence of cranio spine difunction in patients with temporomandibular difunction

O presente estudo teve como objetivos determinar a prevalência de Disfunções Crânio Cervicais (DCC) em voluntários portadores de Disfunções Temporomandibulares (DTM). Foram se¬lecionados 200 voluntários do serviço de triagem da Faculdade de Odontologia de Piracicaba da Universidade Estadual de Campinas, os quais foram avaliados por meio da ficha clínica ela¬borada pelo Centro de Estudos e Tratamento das Alterações Funcionais do Sistema Estomatognático (CETASE) para o diagnóstico de DTM. Os voluntários que apresentaram sinais e síntomas positivos para as DTM foram submetidos a um novo exame clínico para avaliação de DCC. Os resultados obtidos demonstraram uma prevalência de 69% de DCC em voluntários portadores de DTM. Os sinais e sintomas de maior prevalência para as duas patologias foram presença de ruído articular, dor nas articulações tem poro mandibulares e dor à palpação nos músculos mas¬seter e trapézio. Em conclusão, devido à significante prevalência da associação entre DCC e DTM se torna importante a investigação clínica das estruturas cervicais durantes os exames físicos para o diagnóstico das DTM.

The objective of the present study was to determine the prevalence of Cervical Spine Disfunction (CSD) in volunteers with Temporomandibular Disfunction (TMD). 200 volunteers were selected from the screening service of Dentistry School of Piracicaba, State University of Campinas, which were evaluated by records prepared by the Center for Research and Treatment of Functional Alterations of the Stomatognathic System (CETASE) for the diagnosis of TMD. Volunteers who presented positive signs and symptoms of TMD underwent a new clinical examination for C5D. The results showed a prevalence of 69% of CSD in volunteers with TMD. The most frequently signs and symptoms observed for the two diseases were the presence of joint noise, temporomandibular joint pain, pain on palpation in the masseter and trapezius muscles. In conclusion, due to the significant association between prevalence of CSD and TMD becomes important clinical research of neck structures during the physical examination for the diagnosis ofTMD.