Combretastatins A, B, and D are a group of stilbenes, dihydrostilbenes, phenanthrenes, and macrocyclic lactones that may be found in the bark of the Combretum caffrum tree. Preclinical studies have shown that the lead chemical, combretastatin A-4, is highly cytotoxic and inhibits tubulin polymerisation by interacting with the microtubule's colchicine binding site. The anti-cancer activity of a new series of Schiff bases derived from 2-amino-combretastatin as analogues of combretastatin A-4 (CA-4) was investigated. The structures of the synthesised derivatives were proved using 1 H and 13 C NMR, I.R. spectroscopy and elemental analysis. As tubulin polymerisation inhibitors, several drugs demonstrated excellent anti-proliferative activity. IC 50 values for compounds 8a, 8d, 8c and 8i were 1.6, 1.9, 1.9 and 1.3 µM, respectively. In addition, prepared Schiff bases exhibited anti-proliferative action in several human cell lines derived from various organs, namely, HT-29, MCF-7, and A-549, as well as the non-tumor cell line HEK-273. The Schiff bases substituent at the 2-position of ring A in the combretastatin chemical skeleton may play a significant role in the bioactivity of this group of drugs.