In Silico Metabolomic Analysis of Saxitoxin and Its Analogs

Toxins are used as biological weapons, one of which is marine toxins produced by dinoflagellates and cyanobacteria. Due to their potential toxicity, marine toxins exhibit a broad chemical and biological diversity, making them an exceptional reservoir for drug discovery. Saxitoxin and its analogs (STXs), of which there are about 60, are collectively known as paralytic shellfish toxins (PSTs). STX biosynthesis in dinoflagellates is known to be affected by environmental conditions, which demonstrate varying toxicities. The objective of this study is to evaluate and understand the dynamics of STX and 14 its analogs' activity through Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADME/Tox) profiles to uncover insights into new therapeutic targets. For metabolite profile prediction, we will utilize the MetaTox online server. The Swiss ADME, Deep-PK, and PASS Prediction of Activity Spectra for Substances (PASS) online servers were used to analyze physicochemical properties, pharmaceutically relevant descriptors based on the violation of Lipinski's rule. As a result, all molecules present at least two violations of Lipinski’s rule, such as >5 values in the hydrogen bond donor (HDB) and hydrogen bond acceptor (HDA) parameters. The STX analogs showed more affinity for the sodium channel than STX. However, STX, dcSTX, GTX5, and NeoSTX showed more affinity for the HERG channel. Thus, with the predicted metabolites, as well as their ADME/Tox profile, it will be possible to predict new information and outline new drug development strategies.