Photoactivatable Heptamethine-Based Carbonic Anhydrase Inhibitors Leading to New Anti-Antibacterial Agents.

With the aim to propose innovative antimicrobial agents able to not only selectively inhibit bacterial carbonic anhydrases (CAs) but also to be photoactivated by specific wavelengths, new heptamethine-based compounds decorated with a sulfonamide moiety were synthesized by means of different spacers. The compounds displayed potent CA inhibition and a slight preference for bacterial isoforms. Furthermore, minimal inhibitory and bactericidal concentrations and the cytotoxicity of the compounds were assessed, thus highlighting a promising effect under irradiation against S. epidermidis. The hemolysis activity test showed that these derivatives were not cytotoxic to human red blood cells, further corroborating their favorable selectivity index. This approach led to the discovery of a valuable scaffold for further investigations.

Synthesis, Photophysical Characterization and Evaluation of Biological Properties of C7, a Novel Symmetric Tetra-Imidazolium-Bis-Heterocycle.

A novel symmetric tetra-imidazolium-bis-heterocycle, called C7, was designed and synthesized in a quick two-step pathway, with the objective to synthesize biologically active supramolecular assembly. The synthesized compound was then analyzed for its photophysical properties, for a potential application in theragnostic (fluorescence) or phototherapy (photodynamic therapy, with the production of reactive oxygen species, such as singlet oxygen 1O2). C7 was thus screened for its biological activity, in particular against important human pathogens of viral origin (respiratory viruses such as adenovirus type 2 and human coronavirus 229E) and of fungal and bacterial origin. The compound showed limited antiviral activity, combined with very good antiproliferative activity against breast cancer, and head and neck squamous cell carcinoma models. Interestingly, the selected compound showed excellent antibacterial activity against a large array of Gram-positive and Gram-negative clinically isolated pathogenic bacteria, with a possible inhibitory mechanism on the bacterial cell wall synthesis studied with electron microscopy and molecular docking tools. Collectively, the newly synthesized compound C7 could be considered as a potential lead for the development of new antibacterial treatment, endowed with basic photophysical properties, opening the door towards the future development of phototherapy approaches.

Aspects of Antiviral Strategies Based on Different Phototherapy Approaches: Hit by the Light.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused the COVID-19 pandemic spreading around the world from late 2019, served as a ruthless reminder of the threat viruses pose to global public health. The synthesis of new antiviral drugs, as well as repurposing existing products, is a long-term ongoing process which has challenged the scientific community. One solution could be an effective, accessible, and rapidly available antiviral treatment based on phototherapy (PT). PT has been used to treat several diseases, and relies on the absorption of light by endogenous molecules or exogenous photosensitizers (PS). PT has often been used in cancer treatment and prophylaxis, and as a complement to established chemotherapy and immunotherapy in combined therapeutic strategy. Besides significant applications in anticancer treatment, studies have demonstrated the beneficial impact of PT on respiratory, systemic, emerging, and oncogenic viral infections. The aim of this review was to highlight the potential of PT to combat viral infections by summarizing current progress in photodynamic, photothermal, and photoacoustic approaches. Attention is drawn to the virucidal effect of PT on systemic viruses such as the human immunodeficiency virus and human herpes viruses, including the causative agent of Kaposi sarcoma, human herpes virus (HHV8). PT has good potential for disinfection in anti-norovirus research and against pandemic viruses like SARS-CoV-2.