RESUMO
In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC50 values between 9.7 and 6.03µM. The 8c derivative showed the highest potency against cruzain (IC50=2.4µM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (Eb=-7.39kcal·mol(-1)) indicates interaction (via dipole-dipole) between the hybridized sulfur sp(3) atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.
Assuntos
Tiazolidinas/farmacologia , Tiofenos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Linhagem Celular , Cisteína Endopeptidases , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/farmacologia , Inibidores de Cisteína Proteinase/toxicidade , Glicina/química , Camundongos , Simulação de Acoplamento Molecular , Octoxinol , Proteínas de Protozoários/antagonistas & inibidores , Tiazolidinas/síntese química , Tiazolidinas/toxicidade , Tiofenos/síntese química , Tiofenos/toxicidade , Tioureia/análogos & derivados , Tioureia/síntese química , Tioureia/farmacologia , Tioureia/toxicidade , Tripanossomicidas/síntese química , Tripanossomicidas/toxicidadeRESUMO
A case of basilar impression associated with Arnold-Chiari malformation and with trigeminal neuralgia is reported. The radiological examination of the skull showed marked asymmetry of the petrous bone with the tip of the odontoid apophysis located 30 mm above the McGregor line. Treatment consisted of craiectomy of the posterior fossa and cervical laminetomy (C1 to C3). The postoperative course was uneventful with total disappearance of the trigeminal neuralgia.
Assuntos
Platibasia/complicações , Neuralgia do Trigêmeo/etiologia , Malformação de Arnold-Chiari/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The authors studied nine members of the same family; two among them received surgical treatment for basilar impression and Arnold-Chiari malformation. In the other members of the family, several signs and symptoms of central nervous disease were observed. All patients had the apex of the odontoid apophysis above McGregor's line, 4 mm in the case 9, and 10 mm or more in the others.
Assuntos
Malformação de Arnold-Chiari/genética , Platibasia/genética , Adulto , Idoso , Malformação de Arnold-Chiari/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Platibasia/cirurgiaRESUMO
In order to investigate the clinical factors that might influence the diversity and the degree of Candida species carriage in saliva, we conducted a cross-sectional study with 133 patients with complaints of xerostomia. Anamnesis, oral examination and collection of chewing-stimulated whole saliva were performed. The samples of saliva were kept refrigerated until they were plated onto CHROMagar Candida; cfu were counted and Candida species were identified by standard methods. There was a high prevalence of mixed Candida colonization. No relationship was found between total Candida cfu counts and variables like gender, age, place of origin, underlying diseases, exposure to medications (except antibiotics), daily habits and salivary flow rates. Oral candidiasis, antibiotic exposure and dental prosthesis wearing were associated with relatively high Candida counts in saliva. Low salivary flow rates predisposed to intense colonization by C. albicans and C. parapsilosis.