Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)

Abstract

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC­(C-2.15Phe) and BatxC­(C-2.14Phe)­des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.

Pyrazoline derivatives as promising novel antischistosomal agents

“…b Veber filter 25 : Rotatable bonds ≤ 10; TPSA ≤ 140. c Egan filter 26 : WLOGP ≤ 5.88; TPSA ≤ 131.6. d Muegge filter 27 : 200 ≤ MW ≤ 600; − 2 ≤ XLOGP ≤ 5; TPSA ≤ 150; rings ≤ 7; carbon > 4; heteroatoms > 1; rotatable bonds ≤ 15; HBA ≤ 10; HBD ≤ 5.…”

“…The DMEM contained 1 or 4 mg/mL glucose for Vero and SH-SY5Y cells, respectively. Cytotoxicity assay was performed as previously described 25 , 26 . Briefly, cells were seeded in 96-well plates (Corning) in DMEM medium and incubated with twofold serial drug starting at 200 μM following a 24 h adhesion period at 37 °C in 5% CO 2 .…”

Antioxidant and Neuroprotective Effects of the First Tryptophyllin Found in Snake Venom (Bothrops moojeni)

“…The innate immune system of these animals is composed of a variety of cells and molecules that act as a first line of nonspecific defense against pathogens, including antimicrobial peptides (AMPs), complement system, and leukocytes. , Cathelicidins, for example, are antimicrobial peptides with cationic character due to the presence of positively charged residues (lysine, arginine, and histidine), presenting an amphiphilic structure, varying from 10 to 50 amino acid residues. , These AMPs have been extensively studied and have a remarkable antimicrobial activity . Indeed, cathelicidin-related antimicrobial peptides found in the venom of Bothrops atrox are excellent antimicrobials, acting against Gram-positive and Gram-negative bacteria, as well as antiparasitic activity against Leishmania amazonensis …”

“…7 Indeed, cathelicidin-related antimicrobial peptides found in the venom of Bothrops atrox are excellent antimicrobials, acting against Gram-positive and Gram-negative bacteria, 8 as well as antiparasitic activity against Leishmania amazonensis. 9 In snake venoms, several proteins, enzymes, and peptides have specificity toward different receptors in animal tissues, 10 causing pathophysiological effects. For example, the neurotoxic polypeptide α-bungarotoxin found in the venom of Bungarus multicintictus acts by blocking the nicotinic acetylcholine receptors, resulting in paralysis.…”

Isolamento e caracterização funcional e estrutural de compostos antitumorais de baixo peso molecular da peçonha da serpente Bothrops jararacussu

“…A Batroxicidin, apresentou atividade citotóxica sob microrganismos multidrogas resistentes e células tumorais renais murinas da linhagem LLC-MK2, mas ainda não há relatos a cerca de sua atividade anticâncer em linhagens humanas (DEMATEI et al, 2021). A Lutzicidin, identificada na peçonha de B. lutzi, devido à alta similaridade estrutural com a Batroxicidin, as quais variam em apenas 2 resíduos de aminoácidos no centro de sua cadeia, ainda não foi sintetizada e avaliada.…”