Plectranthus‐derived Abietanes as Protein Kinase C‐δ Activators: In Silico Design, Human Serum Albumin Interaction, and Stability Evaluation

Cancer remains a major global health challenge. Among protein kinases (PKCs), PKC‐δ acts as a tumor suppressor in colon cancer and represents a valuable therapeutic target. Human serum albumin (HSA) is gaining attention as an efficient drug carrier, while Plectranthus spp. offers a rich source of bioactive compounds. One such molecule is 7α‐acetoxy‐6β‐hydroxyroyleanone (Roy, 1 ), a cytotoxic abietane diterpenoid with modifiable hydroxyl groups, making it a promising scaffold for drug development. This study aimed to design a theoretical library of Roy 1 derivatives targeting PKC‐δ. Hydroxyl groups at positions C6 and C12 were modified to explore interactions through molecular docking against the PKC‐δ regulatory domain (1PTR). Compound 16 emerged as the most promising candidate. Additionally, the binding of Roy 1 to HSA was evaluated by steady‐state fluorimetry, revealing moderate affinity near Trp‐214 and enhancing the thermal stability of the complex. Roy 1 exhibits excellent aqueous stability (0.1 mM, pH 7.4, 37°C), with similar results for two benzoylated derivatives (RoyBz and Roy12Bz), and no ester hydrolysis was detected. These findings highlight Roy 1 ’s potential as a stable, bioactive lead compound for developing PKC‐δ‐targeted therapeutics, with HSA as a suitable delivery vehicle.