Uncovering Streptomyces-Derived Compounds as Cosmeceuticals for the Development of Improved Skin Photoprotection Products: An In Silico Approach to Explore Multi-Targeted Agents

The search for novel photoprotective substances has become a challenge in cosmeceutical research. Streptomyces-derived compounds can serve as a promising source of photoprotective agents to formulate skin photoprotection products, such as sunscreens. This study aimed to identify specialized metabolites with the potential to modulate UV-induced cellular damage in the skin by identifying potential multi-target-directed ligands. Using a combination of ligand- and target-based virtual screening approaches, a public compound library comprising 6524 Streptomyces-derived specialized metabolites was studied for their photoprotective capability. The compounds were initially filtered by safety features and then examined for their ability to interact with key targets in the photodamage pathway by molecular docking. A set of 50 commercially available UV filters was used as the benchmark. The protein–ligand stability of selected Streptomyces-derived compounds was also studied by molecular dynamics (MD) simulations. From the compound library, 1981 compounds were found to meet the safety criteria for topically applied products, such as low skin permeability and low or non-toxicity-alerting substructures. A total of 34 compounds had promising binding scores against crucial targets involved in UV-induced photodamage, such as serotonin-receptor subtype 5-HT2A, platelet-activating factor receptor, IL-1 receptor type 1, epidermal growth factor receptor, and cyclooxygenase-2. Among these compounds, aspergilazine A and phaeochromycin F showed the highest ranked interactions with four of the five targets and triggered complex stabilization over time. Additionally, the predicted UV-absorbing profiles also suggest a UV-filtering effect. Streptomyces is an encouraging biological source of compounds for developing topical products. After in silico protein–ligand interactions, binding mode and stabilization of aspergilazine A and phaeochromycin F led to the discovery of potential candidates as photodamage multi-target inhibitors. Therefore, they can be further explored for the formulation of skin photoprotection products.