Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents.

Skin Cancer (SC) is among the most common type of cancers worldwide. The search for SC therapeutics using molecular modeling strategies as well as considering natural plant-derived products seems to be a promising strategy. The phytochemical Rocaglamide A (Roc-A) and its derivatives rise as an interesting set of reference compounds due to their in vitro cytotoxic activity with SC cell lines. In view of this, we performed a hierarchical virtual screening study considering Roc-A and its derivatives, with the aim to find new chemical entities with potential activity against SC. For this, we selected 15 molecules (Roc-A and 14 derivatives) and initially used them in docking studies to predict their interactions with Checkpoint kinase 1 (Chk1) as a target for SC. This allowed us to compile and use them as a training set to build robust pharmacophore models, validated by Pearson's correlation (p) values and hierarchical cluster analysis (HCA), subsequentially submitted to prospective virtual screening using the Molport® database. Outputted compounds were then selected considering their similarities to Roc-A, followed by analyses of predicted toxicity and pharmacokinetic properties as well as of consensus molecular docking using three software. 10 promising compounds were selected and analyzed in terms of their properties and structural features and, also, considering their previous reports in literature. In this way, the 10 promising virtual hits found in this work may represent potential anti-SC agents and further investigations concerning their biological tests shall be conducted.

Theoretical Study of Monoamine Oxidase B Inhibitors as Drug Candidates for Treatment of Parkinson's Disease.

BACKGROUND: Drugs used for Parkinson's disease (PD) are mainly responsible for only relieving major symptoms, but may present several side effects that are typical of such pharmacological treatment. METHODS: This study aimed to use in silico methods for drug designing inhibitors of the PD therapeutic target, monoamine oxidase B (MAO-B). Thus, 20 MAO-B inhibitors from the BindingDB database were selected followed by a calculation of their descriptors at DFT B3LYP/6-31G** level of theory. RESULTS: Statistical analysis considering a Pearson correlation matrix led to the selection of electrophilicity index as a descriptor related to the biological activity of inhibitors. Furthermore, based on the prediction of suitable ADME/Tox properties, the molecule CID 54583085 was selected as a template to carry out structural modifications to obtain 3 analogues, whereas molecules B and C showed significant improvement in mutagenicity and carcinogenicity, in relation to the template. CONCLUSION: Thus, it is concluded that the proposed modifications led us to satisfactory results, since there was an improvement in the toxicological properties of molecules, however, further studies must be carried out to evaluate their biological activities as possible MAO-B inhibitors for PD treatment.

Chemical profiling of Curatella americana Linn leaves by UPLC-HRMS and its wound healing activity in mice.

Based on ethnopharmacological studies, a lot of plants, as well as its compounds, have been investigated for the potential use as wound healing agents. In Brazil, Curatella americana is traditionally used by local people to treat wounds, ulcers and inflammations. However, to the best of our knowledge, its traditional use in the treatment of wounds has not been validated by a scientific study. Here, some compounds, many of them flavonoids, were identified in the hydroethanolic extract from the leaves of C. americana (HECA) by LC-HRMS and LC-MS/MS. Besides that, solutions containing different concentrations of HECA and a gel produced with this extract were evaluated for its antimicrobial, coagulant and wound healing activities on an excision mouse wound model as well as its acute dermal safety. A total of thirteen compounds were identified in HECA, mainly quercetin, kaempferol and glucoside derivatives of both, besides catechin and epicatechin known as wound healing agents. The group treated with 1% of HECA exhibited highest wound healing activity and best rate of wound contraction confirmed by histopathology results. The present study provides scientific evidence of, this extract (HECA) possess remarkable wound healing activity, thereby, supporting the traditional use.