The diterpene 7α-acetoxy-6β-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6β-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.

中文翻译：

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探索左手香属 7α-乙酰氧基-6β-羟基豆蔻酮半合成衍生物的抗癌潜力：计算机模拟方法

从 Plectranthus grandidentatus 中分离出的二萜 7α-乙酰氧基-6β-羟基豆蔻酮具有良好的抗菌、抗炎和抗癌特性。然而，其生物活性可以通过半合成对此类天然产物进行战略性结构修饰来增强。通过化学吸收、分布、代谢、排泄和毒性（ADMET）预测、量子力学计算、分子对接和分子动力学模拟，在计算机上分析了 7α-乙酰氧基-6β-羟基豆蔻酮和五种衍生物的抗癌潜力。蛋白质靶标包括细胞凋亡和细胞增殖的调节因子。此外，网络药理学被用来识别潜在的靶点和信号通路。衍生物 7α-乙酰氧基-6β-羟基-12-O-(2-氟酰基)royleanone 和 7α-乙酰氧基-6β-(4-氟)苯甲酰基-12-O-(4-氟)苯甲酰royleanone 实现了对其的高预测结合亲和力各自的蛋白质面板，具有稳定的分子动力学轨迹。两种化合物均表现出良好的 ADMET 参数和毒性特征。它们的稳定性和反应性通过几何优化得到了证实。网络分析揭示了它们参与癌症相关途径。我们的研究结果证明将 7α-acetoxy-6β-羟基-12-O-(2-氟酰基)royleanone 和 7α-acetoxy-6β-(4-氟)苯甲氧基-12-O-(4-氟)苯甲酰基royleanone 包含在作为潜在抗癌剂的体外分析。我们的结合模式分析和稳定性模拟表明它们作为选择性抑制剂的潜力。这些数据将指导其结构优化、增强功效和药物相似性的研究。