Publications by authors named "Edgar A Pinos-Tamayo"

2 Publications

  • Page 1 of 1

Dissection of phospholipases A reveals multifaceted peptides targeting cancer cells, Leishmania and bacteria.

Bioorg Chem 2021 May 31;114:105041. Epub 2021 May 31.

Biomolecules Discovery Group, Universidad Regional Amazónica Ikiam, Km 7 Via Muyuna, Tena, Napo, Ecuador. Electronic address:

Cationic peptides bio-inspired by natural toxins have been recognized as an efficient strategy for the treatment of different health problems. Due to the specific interaction with substrates from biological membranes, snake venom phospholipases (PLAs) represent valuable scaffolds for the research and development of short peptides targeting parasites, bacteria, and cancer cells. Considering this, we evaluated the in vitro therapeutic potential of three biomimetic peptides (pCergo, pBmTxJ and pBmje) based on three different amino acid sequences from Asp49 PLAs. First, short amino acid sequences (12-17 in length) derived from these membranolytic toxins were selected using a combination of bioinformatics tools, including AntiCP, AMPA, PepDraw, ToxinPred, and HemoPI. The peptide, from each polypeptide sequence, with the greatest average antimicrobial index, no toxicity, and no hemolysis predicted was synthesized, purified, and characterized. According to in vitro assays performed, pBmje showed moderate cytotoxicity specifically against MCF-7 (breast cancer cells) with an EC of 464.85 µM, whereas pBmTxJ showed an antimicrobial effect against Staphylococcus aureus (ATCC 25923) with an MIC of 37.5 µM, and pCergo against E. coli (ATCC 25922) with an MIC of 75 µM. In addition, pCergo showed antileishmanial activity with an EC of 93.69 µM and 110.40 µM against promastigotes of Leishmania braziliensis and L. amazonensis, respectively. Altogether, these results confirmed the versatility of PLA-derived synthetic peptides, highlighting the relevance of the use of these membrane-interacting toxins as specific archetypes for drug design focused on public health problems.
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http://dx.doi.org/10.1016/j.bioorg.2021.105041DOI Listing
May 2021

Peptides to Tackle Leishmaniasis: Current Status and Future Directions.

Int J Mol Sci 2021 Apr 22;22(9). Epub 2021 Apr 22.

Biomolecules Discovery Group, Universidad Regional Amazónica Ikiam, Tena 150150, Ecuador.

Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources-amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others-or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.
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http://dx.doi.org/10.3390/ijms22094400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122823PMC
April 2021
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