Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses

Abstract

Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations.

Membrane-Targeting Perylenylethynylphenols Inactivate Medically Important Coronaviruses via the Singlet Oxygen Photogeneration Mechanism

“…The 1 O2-induced formation of short polar lipids dramatically changes the membrane rheology, and, in the case of virion envelopes, their ability to fuse with the host cellular membrane [23,24]. Generally, membrane-targeting 1 O2-generating compounds show remarkable antiviral effects in vitro, e.g., arylidene rhodanines (LJ compounds) [25][26][27][28], methylene blue [29][30][31][32], riboflavin derivatives [33], iodinated BODIPY [34], fullerene derivatives [35], phthalocyanines [36][37][38], pheophorbide a [39] and other porphyrins [40][41][42], AIE compounds [43], alkyl Rose Bengal derivatives [44], and a genetically encoded photosensitizer [45].…”

Evaluating the Efficiency of Chitosan‐Graphene Oxide Hybrid Hydrogels as Drug Delivery Systems

“…The novelty of our approach is the set-up of a highly reproducible single step reaction consisting in tripolyphosphate (TPP)-based ionic gelation, to prepare a biodegradable hydrogel consisting of multiple components with tailored activities: 1) CS acts as the biocompatible and biodegradable element with high water retention capability; [23] 2) GO acts as antimicrobial surface, enhances the drug loading capability making the release profile prolonged over time and allows the modulation by an external voltage; [24,25] TPP, a non-toxic polyanion able to crosslink CS chains, is widely recognized as a safe (GRAS 582.6810) reactant by the Food and Drug Administration; [26] and 3) RB is used as a model for bioactive molecules with antimicrobial activity. [27,28] The rationale behind the choice of CS, GO for the design of the hybrid hydrogel relies in the need to match the desired effects with the peculiarities of the system components which are expected to influence the performance of the final device. In this context, polysaccharides, particularly chitosan, are widely explored due to their key properties.…”