Metastatic cancer is a global concern. Invasion and metastasis are the hallmarks of cancer responsible for most cancer morbidity and mortality. Studies have suggested that an attack against these processes could cause a major breakthrough in cancer therapeutics. This research aimed at building the dataset of marine compounds reported to have effects on invasion and metastasis, and investigating their binding interactions, and stability with dual-specificity tyrosine regulated kinase 2 (DYRK2) through rigid receptor molecular docking, and molecular dynamics studies.
51 chemical compounds from 28 different species of marine organisms reported to have migrastatic activity in vitro/vivo were used. The dataset and SMILE strings for this study was generated using Chemsketch. The SwissADME (http://www.swissadme.ch/) and pkCSM (https://biosig.lab.uq.edu.au/pkcsm/prediction) webservers were used to predict the physiochemical and pharmacokinetic properties of the compounds after which ProTox-II (https://tox-new.charite.de/protox_II) was used to further evaluate their toxicity parameters. Compounds with drug-like properties were then subjected to in silico studies, investigating their binding interactions and stability with dual-specificity tyrosine regulated kinase 2 (DYRK2) through rigid receptor molecular docking, and molecular dynamics studies.
The compounds isolated from these organisms were mainly alkaloids and peptides, phenolics and polysaccharides with varying physicochemical, pharmacokinetic and toxicity properties. 4 compounds with high binding affinity, stability at the binding cavity of DYRK2, and low toxicity were selected, of which compound 5, normonanchoidine H, an alkaloid isolated from Monanchora pulchra, and compound 26, Bastadin A from Lanthella basta were the most promising lead molecules.
We found that 51 chemical compounds from 28 different species of marine organisms were reported in literature to have migrastatic activity in vitro/vivo. Both molecular docking and molecular dynamics studies corroborated the in vitro/in vivo studies. Compounds 5 and 26, due to their high binding affinity to DYRK2, good pharmacokinetic profiles, low risks of toxicity and high stability in the binding site of the protein, have been found as potential lead molecules towards the development of efficacious and low risk toxic migrastatics.