Breast cancer is the most prevalent cancer worldwide. Plectranthus spp. have been used in traditional medicine for various ailments, including cancer, and its bioactive components have been investigated for their potential anticancer effects. In particular, the compound 7α-acetoxy-6βhydroxyroyleanone (Roy, 1) displayed promising antiproliferative activity against several cancer cell lines. However, Roy 1 is highly hydrophobic and consequently has low water solubility, limiting its therapeutic use. Nanoformulations offer a potential solution. Accordingly, Roy 1 was investigated as a lead compound for the development of new antitumoral drugs through extraction optimization from P. grandidentatus, study of reactivity, evaluation of aqueous stability, and synthesis of Roy 1 gold nanoparticles (NPs). The acetonic ultrasound assisted extraction method was optimized by performing three cycles of 30 minutes each, which improved the isolation yield (46.8 ± 11.25 μg.mg^-1). The reactivity of Roy 1 was explored to prepare new bioactive esters. Consequently, a new (4) and three known (2, 3, and 5) ester derivatives were prepared. Considering the stability study, compounds 1, 2, and 3 were evaluated and results indicate that all of them were completely water stable (concentration of 0.1 mM, pH 7.4, and 37°C, for 10 days). Moreover, 1_NPs were successfully synthetized and exhibit promising physicochemical characteristics and an impressive 74.9% drug conjugation efficiency. Additionally, natural 1, derivatives 2-5, and 1_NPs system exhibit significant activity against the aggressive breast cancer cell line, MDA-MB-231. These findings represent a significant advancement in our ongoing efforts to develop novel therapeutic agents and drug delivery platforms.