Characterization of Drug-like Chemical Space for Cytotoxic Marine Metabolites Using Multivariate Methods

[Image: see text] In the last few decades, marine metabolites have been exploited to find commercially viable products in several areas. In this article, molecular descriptors [log P, mass, total polar surface area (TPSA), H-bond donor, H-bond acceptor, and the number of rotatable bonds] for the marine-derived cytotoxic metabolites were calculated and compared with marketed anticancer drugs to understand their position in the drug-like space. Marine-based cytotoxic metabolites are divided into highly toxic (HT) and moderately toxic (MT) classes. The marketed anticancer drugs complied well with Lipinski’s rule of five for all molecular descriptors. The majority of HT and MT metabolites complied solely with H-bond donors and a number of rotatable bonds with the Lipinski cutoff values. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were also performed using 73 molecular descriptors on an ensemble of highly cytotoxic or moderately cytotoxic marine metabolites and the marketed reference drugs. The HCA results showed that 12% of marine metabolites clustered with the marketed anticancer drugs and many of them had structural scaffold homology. The PCA results revealed the presence of a clear distinction between the cytotoxic marine metabolites and the marketed anticancer drugs. Results indicate that mass, TPSA, and log P are the vital parameters and the careful optimization of these parameters for marine cytotoxic metabolites may generate more meaningful anticancer candidates in the future.