Comparative In Silico Analysis of Solanum tuberosum and Citrus sinensis Phytochemicals Synergy against Melanogenesis: Drug-Likeness, and Tyrosinase Inhibition Potential: IC₅₀, logP, HBD, HBA

Abstract Chemical depigmenting agents and their increasing toxicity and adverse dermatologic effects on skin lightening have prompted a shift toward botanical alternatives. But for such compounds to be successfully developed into medications or cosmeceuticals, a thorough understanding of their physicochemical properties which control permeability, solubility, and ultimately bioactivity is necessary. Citrus sinensis and Solanum tuberosum are compared phytochemically in this study. To assess and compare the five main phytochemicals Nobiletin, Hesperidin, Ascorbic Acid, Chlorogenic Acid, and Malvidin—in terms of their lipophilicity (logP), hydrogen bond donors (HBD), hydrogen bond acceptors (HBA), and compliance with Lipinski's Rule of Five. Then, connect these parameters to the phytochemicals' capacity to inhibit tyrosinase and antioxidant activity. Using in silico technologies (PubChem, SwissADME), each substance was examined to identify important physicochemical characteristics. The results for logP, HBD, HBA, and Ro5 infractions were interpreted in ascending order. The results, which focused on tyrosinase inhibition and antioxidant processes, were correlated with their known or anticipated biological activities. In order to promote passive permeability and efficient enzymatic interaction, nobiletin, malvidin, and ascorbic acid displayed perfect profiles with balanced lipophilicity, no Ro5 violations, and controllable hydrogen bonding properties. High polarity and many hydrogen bonding characteristics were demonstrated by hesperidin and chlorogenic acid, which improve antioxidant potential but hinder membrane diffusion and oral bioavailability without improving formulation. The therapeutic viability of natural substances is significantly influenced by drug-likeness criteria, as this study demonstrates. The choice of nobiletin and malvidin as the main options for tyrosinase-targeted depigmentation treatments is supported by the combined physicochemical For upcoming experimental validation and formulation-focused development of phytochemical-based therapeutics, our in silico insights offer a predictive basis.