Computational and pharmacokinetic evaluation of Distichochlamys citrea compounds for cancer treatment

Abstract

The apoptosis pathway plays a crucial role in regulating cell survival and death. This regulatory mechanism involves two main groups of proteins: anti-apoptotic and pro-apoptotic members of the Bcl-2 family. An imbalance that favors anti-apoptotic proteins, particularly the overexpression of Bcl-xL, is strongly associated with cancer progression across various tumor types. As a result, targeted cancer therapies focusing on Bcl-xL have been the subject of intense research in recent decades. Studies exploring natural compounds from medicinal plants present a promising complementary approach to cancer treatment alongside traditional anticancer drugs. This study examined compounds identified in Distichochlamys citrea, an endemic Vietnamese plant known for its anticancer properties. We employed molecular docking and molecular dynamics simulations to identify compounds from D. citrea with a strong binding affinity toward the Bcl-xL protein. Findings of the present study revealed that two molecules, i.e., Platyphyllone and 5-O-caffeoylquinic acid, bind stably and tightly to the hydrophobic groove of Bcl-xL, suggesting potential inhibitory effects. In-silico analyses of their pharmacokinetic and pharmacodynamic properties indicate that these molecules possess anticancer, antimetastatic, anti-mitotic, and apoptosis-inducing characteristics. Furthermore, both compounds adhere well to Lipinski's rule and exhibit desirable drug-like properties, making them potential candidates for high-dose oral administration without toxicity. In addition to being present in D. citrea, Platyphyllone and 5-O-caffeoylquinic acid are also found in many commonly consumed plants. These findings contribute to the scientific basis for further investigation into the molecular structure and bioactivity of Platyphyllone and 5-O-caffeoylquinic acid as potential cancer treatments.