Computational study Catharanthus roseus L. essential oil extract as potential Pan-PI3K inhibitor

Catharanthus roseus L. is a plant commonly found in Indonesia. C. roseus is known to have anticancer activity due to its alkaloid content. However, C. roseus also contains essential oils (EOs) that have been understudied regarding their potential as anticancer activity. This study aimed to analyze C. roseus EOs as inhibitors of wildtype and mutated PI3K compared with its known pan-inhibitor. Our study was conducted by choosing EOs from literature and database, then evaluated based on drug-likeness. Way2Drug analyzed the bioactivity of each EO according to anticancer parameters chosen, following EOs docked with PI3K ATP-binding domain (ABD) and RAS-binding domain (RBD) used PyRx-0.8 with specific binding sites and visualized by BIOVIA Discovery Studio ver 21.1.0. The result showed EOs have potential as an inhibitor of PI3K based on their binding affinity to ABD and RBD compared to the pan-inhibitor (GDC0941, CH3251799, ZSTK474, and Wortmannin) as drug control. The most potential of C. roseus EO is Limonene, which has the second-lowest binding affinity to PI3K in both the RBD wildtype and mutation protein model. In detail, GDC0941 has the lowest binding affinity as drug control, followed by Wortmannin, while Limonene is the fourth lowest on ABD. Besides, ZSTK474 has the lowest binding affinity, followed by Limonene as the second-lowest RBD. Furthermore, because of its affinity to interact with ABD and RBD active sites, limonene has the potential to act as a pan-inhibitor. In conclusion, this research indicated that C. roseus EO could act as a pan-inhibitor of PI3K with Limonene having the lowest binding affinity to ABD and RBD compared with GDC0941, Wortmannin, ZSTK474, and CH5132799. However, a more comprehensive study needs to be carried out to strengthen the facts and demonstrate the reliability of the results.