Background. Skin wounds are closely correlated with opportunistic infections and sepsis risk. Due to the need of more efficient healing drugs, animal peptides are emerging as new molecular platforms to accelerate skin wound closure and to prevent and control bacterial infection. Aim. The aim of this study was to evaluate the preclinical evidence on the impact of animal peptides on skin wound healing. In addition, we carried out a critical analysis of the studies’ methodological quality. Main Methods. This systematic review was performed according to the PRISMA guidelines, using a structured search on the PubMed-Medline, Scopus, and Web of Science platforms to retrieve studies published until August 25, 2020 at 3 : 00 pm. The studies included were limited to those that used animal models, investigated the effect of animal peptides with no association with other compounds on wound healing, and that were published in English. Bias analysis and methodological quality assessments were examined through the SYRCLE’s RoB tool. Results. Thirty studies were identified using the PRISMA workflow. In general, animal peptides were effective in accelerating skin wound healing, especially by increasing cellular proliferation, neoangiogenesis, colagenogenesis, and reepithelialization. Considering standardized methodological quality indicators, we identified a marked heterogeneity in research protocols and a high risk of bias associated with limited characterization of the experimental designs. Conclusion. Animal peptides show a remarkable healing potential with biotechnological relevance for regenerative medicine. However, rigorous experimental approaches are still required to clearly delimit the mechanisms underlying the healing effects and the risk-benefit ratio attributed to peptide-based treatments.
Alzheimer's disease (AD) is a neurodegenerative, polygenic and multifactorial disorder associated with aging. Despite advances in investments, so far there is no effective treatment for this dementia. Various enzymatic targets have been and are still being studied in an attempt to discover new drugs for the treatment of AD; however, Rab GTPases are still relatively unexplored. These enzymes regulate cellular processes by alternating of GDP and GTP nucleotides. Studies have shown that the knockdown of Rab10 reduces the production of Aβ42 peptides in the brain parenchyma, making it a promising target for the treatment of AD. In order to identify potential Rab10 inhibitors, the structure-based virtual screening (SBVS) technique was used considering a subset of 80763 natural compounds of ZINC15 database. Tertiary structure of Rab10 was obtained from the Protein Data Bank (PDB) and the Autodock Vina program was used in the SBVS, carried out in three sequential steps to filter potential bioactive substances against this enzyme. The SBVS protocol was validated by redocking the co-crystallized GNP nucleotide and the binding energies of the GDP and GTP nucleotides were used as controls in the pharmacodynamic analysis. Thus, it was possible to select 45 compounds with binding energy less or equal -11 Kcal.mol -1 . Absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties of these compounds were evaluated by the SwissADME program, where it was possible to identify 6 promising molecules. The resulting complexes were subjected to molecular dynamics simulations to analyze the pharmacodynamics over time. The results suggest that the compound ZINC4090657 (derived from quinolizidine) and the compounds ZINC4000106 and ZINC0630250 (derived from coumarin) have favorable pharmacological characteristics for the inhibition of Rab10, with ZINC4090657 being the most promising one.
Leishmaniasis, a neglected tropical disease with a high worldwide incidence, is considered a public health issue in Minas Gerais and Brazil, with a high degree of morbidity, not to mention the lack of therapeutic arsenal. The cysteine protease (rCPB2.8) and cyclin dependent kinase (CRK3), important enzymes for the parasite’s feasibility, were the targets chosen for investigation of the new drugs. The following study aimed to analyze several oximic derivatives starting from safrol, which can present an affinity profile for selected molecular targets using tools from molecular modeling and bioinformatics, planning and synthesis of brand new substances being tested for leishmanicidal drugs. The study allowed to verify that three oximic derivatives (5a, 5f and 5h) presented high affinity for the CRK3 enzyme, and that the compounds 5c and 5g presented good interaction by the amino acids of the catalytic site of the rCPB2.8 enzyme with atomic distances capable of generating covalent bonds, which are essential for enzyme inhibitory activity.
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