RESUMO
Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy-quinone core were considered for developing new anti-T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure-activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy-quinones with higher potency against the protozoan parasite T. cruzi.
Assuntos
Benzoquinonas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Benzoquinonas/química , Relação Dose-Resposta a Droga , Técnicas Eletroquímicas , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/químicaRESUMO
A series of N-acyl-2,5-dimethoxyphenyl-1H-benzimidazoles were designed based on a CoMFA model for cannabinoid receptor type 1 (CB1) ligands. Compounds were synthesized and radioligand binding affinity assays were performed. Eight novel benzimidazoles exhibited affinity for the CB1 receptor in the nanomolar range, and the most promising derivative compound 5 displayed a K(i) value of 1.2 nM when compared to CP55,940. These results confirm our previously reported QSAR model on benzimidazole derivatives, providing new information for the development of small molecules with high CB1 affinity.
Assuntos
Benzimidazóis/síntese química , Benzimidazóis/metabolismo , Agonistas de Receptores de Canabinoides/síntese química , Agonistas de Receptores de Canabinoides/metabolismo , Desenho de Fármacos , Receptor CB1 de Canabinoide/metabolismo , Benzimidazóis/farmacologia , Sítios de Ligação , Ligação Competitiva , Agonistas de Receptores de Canabinoides/farmacologia , Desenho Assistido por Computador , Cicloexanóis/metabolismo , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Conformação Proteica , Relação Quantitativa Estrutura-Atividade , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/químicaRESUMO
BACKGROUND: Prevention and early diagnosis have the greatest potential for public health and are the most effective method in the long-term to control oral cancer. The aim was to apply PAP staining together with AgNOR staining and morphometric analysis in oral exfoliative cytology, to determine the sensitivity and specificity of these methods in the detection of malignant changes for the purposes of both initial population monitoring and follow-up. METHODS: AgNOR, Papanicolau, and morphometric tests were conducted in samples of patients with oral cancer, oral potentially malignant disorders and controls (opposite side of lesions). Specificity and sensitivity values for each stain method and the curve under ROC area were estimated. RESULTS: The diagnostic variables which allowed greatest accuracy in identifying malignancy relative to the healthy control were cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio. CONCLUSIONS: The total number of AgNOR is a reliable marker for detecting neoplastic cells; this method increases sensitivity and specificity by decreasing the likelihood of false negatives or positives, as the accuracy obtained was 90%. It is also a low-cost, non-invasive, simple methodology that can be recommended to help the early detection of oral cancer and monitoring of patients with a first diagnosis of cancer.
Assuntos
Corantes , Citodiagnóstico/métodos , Detecção Precoce de Câncer/métodos , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Nucleares/ultraestrutura , Área Sob a Curva , Núcleo Celular/ultraestrutura , Estudos Transversais , Citodiagnóstico/estatística & dados numéricos , Citoplasma/ultraestrutura , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/patologia , Líquen Plano Bucal/diagnóstico , Líquen Plano Bucal/patologia , Masculino , Pessoa de Meia-Idade , Região Organizadora do Nucléolo/ultraestrutura , Teste de Papanicolaou/estatística & dados numéricos , Curva ROC , Sensibilidade e Especificidade , Coloração pela Prata/estatística & dados numéricos , Adulto JovemRESUMO
En la práctica odontológica hay exposición a riesgos biológicos. En este trabajo indagamos: qué conocimientos sobre dichos riesgos tienen los alumnos, pues representan una problemática de morbi-mortalidad a nivel mundial, nacional y local; y si saben cómo prevenirlos y cómo proceder ante un accidente. Se encuestaron 192 estudiantes del último año de la Facultad de Odontología (UNC). El 95% afirmó conocer los riesgos vinculados con enfermedades infectocontagiosas, pero en general no conocen cuáles son. Con respecto a la profilaxis de disposición, las respuestas fueron incorrectas. El 94 % afirmó conocer los procedimientos ante un accidente de trabajo, pero hubo respuestas imprecisas y desconocimiento sobre los protocolos a seguir. De este estudio inferimos que la mayoría de los alumnos no percibe la vinculación entre riesgo- enfermedad, no conoce totalmente los protocolos relacionados a exposición con material biológico e inmunización , ni la conducta a seguir ante accidentes de trabajo en la práctica clínica.
Assuntos
Humanos , Estudantes de Odontologia , Odontologia , Prevenção de Doenças , RiscoRESUMO
En la práctica odontológica hay exposición a riesgos biológicos. En este trabajo indagamos: qué conocimientos sobre dichos riesgos tienen los alumnos, pues representan una problemática de morbi-mortalidad a nivel mundial, nacional y local; y si saben cómo prevenirlos y cómo proceder ante un accidente. Se encuestaron 192 estudiantes del último año de la Facultad de Odontología (UNC). El 95% afirmó conocer los riesgos vinculados con enfermedades infectocontagiosas, pero en general no conocen cuáles son. Con respecto a la profilaxis de disposición, las respuestas fueron incorrectas. El 94 % afirmó conocer los procedimientos ante un accidente de trabajo, pero hubo respuestas imprecisas y desconocimiento sobre los protocolos a seguir. De este estudio inferimos que la mayoría de los alumnos no percibe la vinculación entre riesgo- enfermedad, no conoce totalmente los protocolos relacionados a exposición con material biológico e inmunización , ni la conducta a seguir ante accidentes de trabajo en la práctica clínica.(AU)