In Silico Study Examining New Phenylpropanoids Targets with Antidepressant Activity.

BACKGROUND: Natural products, such as phenylpropanoids, which are found in essential oils derived from aromatic plants, have been explored during non-clinical psychopharmacology studies, to discover new molecules with relevant pharmacological activities in the central nervous system, especially antidepressant and anxiolytic activities. Major depressive disorder is a highly debilitating psychiatric disorder and is considered to be a disabling public health problem, worldwide, as a primary factor associated with suicide. Current clinically administered antidepressants have late-onset therapeutic actions, are associated with several side effects, and clinical studies have reported that some patients do not respond well to treatment or reach complete remission. OBJECTIVE: To review important new targets for antidepressant activity and to select phenylpropanoids with antidepressant activity, using Molegro Virtual Docker and Ossis Data Warris, and to verify substances with more promising antidepressant activity. RESULTS AND CONCLUSION: An in silico molecular modeling study, based on homology, was conducted to determine the three-dimensional structure of the 5-hydroxytryptamine 2A receptor (5- HT2AR), then molecular docking studies were performed and the predisposition for cytotoxicity risk among identified molecules was examined. A model for 5-HT2AR homology, with satisfactory results, was obtained indicating the good stereochemical quality of the model. The phenylpropanoid 4-allyl-2,6-dimethoxyphenol showed the lowest binding energy for 5-HT2AR, with results relevant to the L-arginine/nitric oxide (NO)/cGMP pathway, and showed no toxicity within the parameters of mutagenicity, carcinogenicity, reproductive system toxicity, and skin-tissue irritability, when evaluated in silico; therefore, this molecule can be considered promising for the investigation of antidepressant activity.

Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.

Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific - PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.