Effect of the
compounds on the MT network and the nuclear morphology
of A549 cells. Effect of dictyostatin analogues 4, 5, 6, 8, 9, 10, and 11 and hybrid molecules 12, 13, 14, and 15 on the MT network,
the mitotic spindle, and the nuclear morphology of A549 cells in comparison
with untreated cells (DMSO), cells treated with paclitaxel, and the
reference parent compounds dictyostatin and discodermolide. Cells
were incubated for 24 h in the presence of DMSO (A, A′), paclitaxel
100 nM (B, B′), dictyostatin 50 nM (C, C′), discodermolide
100 nM (D, D′), 4 250 nM (E, E′), 5 200 nM (F, F′), 6 100 nM (G, G′), 8 200 nM (H, H′), 9 100 nM (I, I′), 10 800 nM (J, J′), 11 2 μM (K, K′), 12 60 nM (L, L′), 13 1.8 μM (M,
M′), 14 6 μM (N, N′), and 15 8 μM (O, O′). MTs (A, B, C, D, E, F, G, H, I, J, K,
L, M, N, and O) are labeled with the DM1A antibody against α-tubulin,
whereas DNA (A′, B′, C′, D′, E′,
F′, G′, H′, I′, J′, K′,
L′, M′, N′, and O′) is marked with Hoechst
33342. The insets (A, A′, B, B′, C, C′, the latest
representative for all ligands examined) show the mitotic spindles
in the same preparations. The bar at O′ represents 10 μm,
with all panels showing the same magnification.