Mygalin: An Acylpolyamine With Bactericidal Activity

Abstract

Inappropriate use of antibiotics favors the selection and spread of resistant bacteria. To reduce the spread of these bacteria, finding new molecules with activity is urgent and necessary. Several polyamine analogs have been constructed and used to control microorganisms and tumor cells. Mygalin is a synthetic acylpolyamine, which are analogs of spermidine, derived from the hemolymph of the spider Acanthoscurria gomesiana. The effective activity of polyamines and their analogs has been associated with their structure. The presence of two acyl groups in the Mygalin structure may give this molecule a specific antibacterial activity. The aim of this study was to identify the mechanisms involved in the interaction of Mygalin with Escherichia coli to clarify its antimicrobial action. The results indicated that Mygalin exhibits intense dose and time-dependent bactericidal activity. Treatment of E. coli with this molecule caused membrane rupture, inhibition of DNA synthesis, DNA damage, and morphological changes. The esterase activity increased along with the intracellular production of reactive oxygen species (ROS) after treatment of the bacteria with Mygalin. In addition, this molecule was able to sequester iron and bind to LPS. We have shown that Mygalin has bactericidal activity with underlying mechanisms involving ROS generation and chelation of iron ions that are necessary for bacterial metabolism, which may contribute to its microbicidal activity. Taken together, our data suggest that Mygalin can be explored as a new alternative drug with antimicrobial potential against Gram-negative bacteria or other infectious agents.

Brazilian Theraphosidae: a toxicological point of view

“…Mygalin was subjected to multiple tests to elucidate the mechanisms responsible for the antimicrobial activity against E. coli. In a viability assay, mygalin (0.5 mM) was more effective than H 2 O 2 (1 mM) [28]. Alkaline electrophoresis gel showed that mygalin causes oxidative DNA damage, which was also observed in E. coli model by confocal microscopy.…”

“…DAPI is a fluorescent dye that intercalates with DNA double-helix and is commonly used to evaluate structural damage on DNA. Filamentation assay with 10 6 CFU/mL treated with 0.5 mM for 3h revealed the capacity of mygalin to interfere on cell division by binding to DNA, causing inhibition of its synthesis in vivo [28].…”

Acanthoscurria gomesiana spider‐derived synthetic mygalin in the dorsal raphe nucleus modulates acute and chronic pain

“…The compound mygalin used in this study is a diacylspermidine synthesized from an analogous molecule present in the hemolymph of the spider Acanthoscurria gomesiana (Araneae, Theraphosidae; Graphical Abstract). [10] Although mygalin is not an acyl-polyamine, the chemical structure of synthesized diacylpespermidine is similar to the natural (n = 9 rats per group). ANOVA, analysis of variance acyl-polyamines.…”

“…Mygalin was diluted into Milli-Q deionized water-vehicle (Millipore); LY 235959, MK-801, and morphine were diluted into saline; CNQX and NBQX were diluted into dimethyl sulfoxide (all from Sigma-Aldrich). Mygalin (>98% purity; Supporting Information) was synthesized at the Centre for Research on Toxins, Immune-Response and Cell Signaling (CeTICS-CEPID), Laboratory for Applied Toxinology-Butantan Institute, and provided by Dr. Pedro Ismael da Silva Jr. As described by Espinoza-Culupú et al, [10] the guidelines for the synthesis followed a classical method of peptide chemistry. [23] The synthesis was carried out in 2-(1H-benzotriazol-1-yl)−1,1,3,3tetramethyluronium hexafluorophosphate solution [24] for the esterification of the carboxyl group of gentisic acid and thus permitting the formation of one carboxamide by formal condensation of two primary amino groups from spermidine with a carboxylic group of two molecules of gentisic acid (2,5-dihydroxybenzoic acid).…”

“…[8] In this sense, natural molecules, such as the class of acylpolyamines (APs) molecules, their derivatives, and analogs could be considered potential alternatives for pain therapeutics. The synthetic molecule Mygalin is a diacylspermidine derivative (previously described as a bis-acyl acylpolyamine named N1, N8-bis [2,5-dihydroxybenzoyl] spermidine of 417 Da) [9,10] (Graphical Abstract). APs have been extensively studied and some of them have been reported to be antagonists of ionotropic glutamatergic receptors, such as the NMDA receptors.…”