Exploring the Antimicrobial and Antitumoral Activities of Naphthoquinone-Grafted Chitosans

Abstract

Biopolymers obtained from natural macromolecules are noteworthy among materials presenting high biocompatibility and adequate biodegradability, as is the case of chitosan (CS), making this biopolymeric compound a suitable drug delivery system. Herein, chemically-modified CS were synthetized using 2,3-dichloro-1,4-naphthoquinone (1,4-NQ) and the sodium salt of 1,2-naphthoquinone-4-sulfonic acid (1,2-NQ), producing 1,4-NQ-CS and 1,2-NQ-CS by three different methods, employing an ethanol and water mixture (EtOH:H2O), EtOH:H2O plus triethylamine and dimethylformamide. The highest substitution degree (SD) of 0.12 was achieved using water/ethanol and triethylamine as the base for 1,4-NQ-CS and 0.54 for 1,2-NQ-CS. All synthesized products were characterized by FTIR, elemental analysis, SEM, TGA, DSC, Raman, and solid-state NMR, confirming the CS modification with 1,4-NQ and 1,2-NQ. Chitosan grafting to 1,4-NQ displayed superior antimicrobial activities against Staphylococcus aureus and Staphylococcus epidermidis associated with improved cytotoxicity and efficacy, indicated by high therapeutic indices, ensuring safe application to human tissue. Although 1,4-NQ-CS inhibited the growth of human mammary adenocarcinoma cells (MDA-MB-231), it is accompanied by cytotoxicity and should be considered with caution. The findings reported herein emphasize that 1,4-NQ-grafted CS may be useful in protecting injured tissue against bacteria, commonly found in skin infections, until complete tissue recovery.

Antimicrobial and wound healing potential of naphthoquinones encapsulated in nanochitosan

“…Among these compounds, chitosan and its several derivatives, such as hydrogel, sponge, film, scaffold, nanoparticle, sulfate or sulfonated-chitosan, among others, can have a positive effect on wound healing. Chitosan is able to interfere in the first three stages; hemostasis, inflammation, proliferation and migration, accelerating wound closure as demonstrated by the migration assay ( Matica et al, 2019 ; Feng et al, 2021 ; Ferreira et al, 2022 ; Pauli et al, 2023b ; Ferreira et al, 2023 ) ( Figure 8 , panels A–B). It has been reported that chitosan promotes blood clot formation by stimulating the expression of the adhesion molecule GP IIb-IIIa at the surface of activated platelets and by stimulating platelet aggregation via electrostatic interactions between positively charged chitosan and negatively charged molecules at the surface of activated platelets.…”

“…Furthermore, chitosan exerts anti-inflammatory effects that reduce inflammatory cytokines, IL-10 and TNF-α, reducing oxidative damage and inflammation ( Yang et al, 2016 ; Mohyuddin et al, 2021 ). However, as mentioned above, antimicrobial effectiveness depends on a variety of intrinsic and extrinsic factors ( Matica et al, 2019 ; Feng et al, 2021 ; Ferreira et al, 2022 ; Pauli et al, 2023b ; Ferreira et al, 2023 ). Moreover, chitosan can stimulate the proliferation of fibroblasts, which compose the remodeled tissue during wound healing.…”

“…Chitosan functionalized with 3,5-dinitro salicylic acid and linked to the antibiotic linezolid, for example, was shown to be effective against methicillin-resistant Staphylococcus aureus (MRSA), among other microorganisms ( Teaima et al, 2020 ). In another assessment, a 2,3-dichloro-1,4-naphthoquinone grafted chitosan exhibited antimicrobial activities against Staphylococcus aureus and Staphylococcus epidermidis , presenting high effectiveness and low cytotoxicity, with high therapeutic indices, ensuring safe human tissue application ( Pauli et al, 2023a ).…”

Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling

“…It is well known that inserting sulfanyl, alkoxy, and/or amino group(s) into the quinone moiety improves its physical, chemical, and biological properties (Ibacache et al, 2016; Ibis et al, 2011; Kadela et al, 2016; Nagar & Dhar, 2022). Reactions between 1,4‐quinones and amines that address biologically important lead molecules have been extensively reported (Lima et al, 2021; Lopez‐Lira et al, 2021; Pauli et al, 2023; Uysal et al, 2021; Varricchio et al, 2020; Yildirim et al, 2022). In line with these studies, we investigated halogenated (brominated and chlorinated) and non‐halogenated plastoquinone (PQ) analogs to understand their antiproliferative profiles against breast cancer cell lines (Jannuzzi et al, 2021, 2022; Yilmaz Goler et al, 2022).…”