Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity

Abstract

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH2), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the action mechanism of BP100, the selectivity of its biological effects, and possible applications are far from consensual. Our group synthesized a fluorescent BP100 analogue containing naphthalimide linked to its N-terminal end, NAPHT-BP100 (Naphthalimide-AAKKLFKKILKYL-NH2). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against transformed cells and bacteria are known. Naphthalimide derived compounds are known to interact with DNA disturbing related processes as replication and transcription, and used as anticancer agents due to this property. A wide variety of techniques were used to demonstrate that NAPHT-BP100 bound to and permeabilized zwitterionic POPC and negatively charged POPC:POPG liposomes and, upon interaction, acquired a α-helical structure. Membrane surface high peptide/lipid ratios triggered complete permeabilization of the liposomes in a detergent-like manner. Membrane disruption was driven by charge neutralization, lipid aggregation, and bilayer destabilization. NAPHT-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes besides causing membrane destabilization. NAPHT-BP100 showed increased antibacterial and hemolytic activities, compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide DNA binding properties, NAPHT-BP100 bound to a large extent to the bacterial membrane and could more efficiently destabilize it. We also speculate that peptide could enter the bacteria cell and interact with its DNA in the cytoplasm.

Synthesis, Spectral Characteristics, Sensing Properties and Microbiological Activity of New Water-Soluble 4-Sulfo-1,8-naphthalimides

“…These properties make this class of compounds, which are widely used as fluorescent markers in biology and medicine, important [9][10][11][12]. With success, 1,8-naphthalimide derivatives are used in the synthesis of compounds with biological activity [13][14][15]. Another cutting-edge field of application of this class of compounds is their use as a signaling fragment in the design of optical molecular devices with sensing properties [16][17][18][19].…”

Insight into the liposomal encapsulation of mono and bis-naphthalimides

“…In this article, the authors investigated the permeabilising capacity of the peptide by changing the lipid composition of the liposomal bilayer by monitoring the fluorescence properties of naphthalimides. 19 Similarly, the fluorescence properties of naphthalimides have been explored to develop selfreporting vectors for nucleic acid delivery using a liposomal carrier. 20,21 To the best of our knowledge, only one article has been published studying the loading of a naphthalene-based diimide derivative (AN169) in liposomes avoiding the use of DMSO as a solubilising agent in in vitro and in vivo experiments.…”

Fluorescent Polymers for Environmental Monitoring: Targeting Pathogens and Metal Contaminants with Naphthalimide Derivatives

“…This adaptability has led to extensive applications in several fields, ranging from selective ion probes and colorful dyes but also in the pharmacological field [12][13][14][15][16]. Several studies reported that compounds which contain a naphthalimide-core scaffold present increased bioactivity, allowing for its usage as an antitumor [17], antidepressant [18], antiviral [19], antiprotozoal [20], anti-inflammatory [21], anti-tuberculosis [22] and antibacterial agent [13]. This increased bioactivity is mainly due to its DNA-binding mechanisms, which are mostly derived from the tricyclic planar ring configuration of the naphthalimide scaffold [12].…”