Unraveling\nthe Potential of Vitamin B<sub>3</sub>‑Derived\nSalts with a Salicylate Anion as Dermal Active Agents for Acne Treatment

This study is focused on the utilization of naturally\noccurring\nsalicylic acid and nicotinamide (vitamin B<sub>3</sub>) in the development\nof novel sustainable Active Pharmaceutical Ingredients (APIs) with\nsignificant potential for treating acne vulgaris. The study highlights\nhow the chemical structure of the cation significantly influences\nsurface activity, lipophilicity, and solubility in aqueous media.\nFurthermore, the new ionic forms of APIs, the synthesis of which was\nassessed with <i>Green Chemistry</i> metrics, exhibited\nvery good antibacterial properties against common pathogens that contribute\nto the development of acne, resulting in remarkable enhancement of\nbiological activity ranging from 200 to as much as 2000 times when\ncompared to salicylic acid alone. The molecular docking studies also\nrevealed the excellent anti-inflammatory activity of <i>N</i>-alkylnicotinamide salicylates comparable to commonly used drugs\n(indomethacin, ibuprofen, and acetylsalicylic acid) and were even\ncharacterized by better IC<sub>50</sub> values than common anti-inflammatory\ndrugs in some cases. The derivative, featuring a decyl substituent\nin the pyridinium ring of nicotinamide, exhibited efficacy against Cutibacterium acnes while displaying favorable water\nsolubility and improved wettability on hydrophobic surfaces, marking\nit as particularly promising. To investigate the impact of the APIs\non the biosphere, the EC<sub>50</sub> parameter was determined against\na model representative of crustaceansArtemia\nfranciscana. The majority of compounds (with the exception\nof the salt containing the dodecyl substituent) could be classified\nas “Relatively Harmless” or “Practically Nontoxic”,\nindicating their potential low environmental impact, which is essential\nin the context of modern drug development.