Integration of NMR studies, computational predictions, and in vitro assays in the search of marine diterpenes with antitumor activity

Abstract

Tubulin is the major component of microtubules and plays a crucial role in cell division. Interferences in the dynamics and functioning of tubulin lead to mitotic arrest, cell cycle block, apoptosis, and cell death, making it an effective target for antimitotic drugs used in cancer chemotherapy (Hadfield et al., 2003;Jordan & Wilson, 2004).Tubulin is a protein of 110 kDa that polymerizes to form microtubules, which generally consist of 13 linear protofilaments assembled around a hollow core of 25 nm. The protofilaments, composed of head-to-tail arrays of tubulin dimers (alpha and beta subunits), are arranged in parallel. Microtubules are polar structures with two distinct ends: a fast-growing plus end and a slow-growing minus end (Janke, 2014). The polymerization process is the responsible