Colchicine is an active pharmaceutical ingredient widely used for treating gout, pericarditis, and familial Mediterranean fever with high antimitotic activity. The photoisomerization of colchicine deactivates its anti-inflammatory and antimitotic properties. However, despite numerous reports on colchicine derivatives, their photostability has not been investigated in detail. This report reveals the effects of UV-induced rearrangement on the structure and reports the biological activity of new N-substituted colchicine derivatives.