Seventeen Schiff bases bearing 2-aminothiophene derivatives were designed and synthesized using molecular simplification. The resulting compounds (4a-4q) were evaluated for their in vitro antifungal activity against dermatophytes. Prediction of their druglikeness and pharmacokinetic properties, establishment of their structure-activity relationships (SAR), and cytotoxic evaluation of the most active compounds were performed. Using an eco-friendly procedure, microwave assisted synthesis resulted in compounds in good yields (35-85%). Compounds 4a-4q presented good druglikeness and pharmacokinetic profiles and no cytotoxicity for any cell line tested up to 100 µM. The compounds presenting the best antifungal profiles were 4e, 4f, 4g, 4k, 4l, 4m, 4o and 4p with more than one minimum inhibitory concentration (MIC) value occurring between 16-64 µg mL-1, thus, in some cases better than the reference drug (fluconazole). SAR testing indicated that the presence of halogens and nitro substituents increases antifungal activity. Taken together, the results demonstrate that 2-aminothiophene derivatives are promising lead compounds for the development of antifungal drugs.

Carbohydrates play a critical role in many cellular processes like disease, growth and development. In this work lectins, proteins that recognizes carbohydrate free or conjugated, were used as histochemical probes for carbohydrates localization in developing human minor salivary gland. Immunohistochemistry for traditional cytoskeleton markers (Cks 7, 8, 13, 14, 19, SMA and Vimentin) was performed and then compared whit lectin histochemistry for PNA, WGA, ConA and UEA-I, specifics for D-galactose, N-acetyl-glucosamine, glucose/mannose and L-fucose respectively. For this, specimens were obtained from tongues and lips of 15 human foetuses at 10-28 weeks of gestation. None of immune cytoskeleton markers were identified in the first stage of development differing from carbohydrate markers. UEA-I, WGA and PNA recognized their specific carbohydrate residues in all stages analyzed varying the staining intensity and cell types. Ck8 and N-acetyl-glucosamine were expressed in canalicular, branching and cytodifferentiation stages while SMA and glucose/mannose were observed in the cytodifferentiation stage one. ConA only recognized myoepithelial cells on cytodifferentiation stages because of this specificity ConA could be used as biomarker of myoepithelial cells on cytodifferentiation. Lectin histochemistry suggests that L-fucose, D-galactose e N-acetyl-glucosamine are intensily and previously expressed than traditional cytoskeletal markers in human minor salivary gland during development.

Los hidratos de carbono tienen un papel crítico en muchos procesos celulares, como la enfermedad, el crecimiento y el desarrollo. Fueron utilizadasas lectinas, proteínas que reconocen los hidratos de carbono libres o conjugados, como sondas de localización histoquímica de los carbohidratos en el desarrollo humano de la glándula salival menor. Se realizó inmunohistoquímica de los marcadores tradicionales del citoesqueleto (CKs 7, 8, 13, 14, 19, SMA y vimentina) y posterior comparación con la histoquímica de lectinas para PNA, WGA, ConA y la UEA-I, específicas para D-galactosa, N-acetil-glucosamina, glucosa/manosa y L-fucosa, respectivamente. Para ello, se obtuvieron muestras de la lengua y de los labios de 15 fetos humanos entre 10-28 semanas de gestación. Ninguno de los marcadores inmunológicos del citoesqueleto se identificaron en la primera etapa del desarrollo, diferente de los marcadores de hidratos de carbono. UEA-I, WGA y PNA reconocen sus residuos específicos de hidratos de carbono en todas las etapas analizadas variando la intensidad de la tinción y los tipos de células. CK8 y N-acetil-glucosamina se expresaron en etapas de canalización, ramificación y citodiferenciación mientras que SMA y la glucosa/manosa se observaron solamente en la etapa de citodiferenciación. ConA sólo se reconoció en las células mioepiteliales en etapas de citodiferenciación. Así, debido a esta especificidad, ConA podría utilizarse como marcador biológico de las células mioepiteliales en la citodiferenciación. La histoquímica de lectinas sugiere que L-fucosa, D-galactosa y N-acetil-glucosamina son intensamente expresadas durante el desarrollo como los marcadores tradicionales del citoesqueleto humanos en las glándulas salivales menores .