DESIGN, SYNTHESIS AND ANTICANCER ACTIVITY OF 9-SUBSTITUTED CARBAZOLE DERIVATIVES

Numerous carbazole derivatives were designed by the Chemsketch software followed by 3D optimization. Docking studies were performed  using AUTODOCK 4.2.6 software to check their binding interactions with eukaryotic topoisomerase-I, based on the crystal structure of Human Topoisomerse-I-DNA complex (PDB ID: 1A35). Results of docking studies of designed carbazole derivatives were compared on the basis of their minimum binding energy with a well known topoisomerase-I inhibitor  i.e. Adriamycin,. Above results were used to find out active compounds and two series of such active compounds i.e. 2-[(4, 5-dihydro-2-substitutedphenyl)imidazol-1-ylamino]-1-(9H-carbazol-9-yl)ethanone (3a-3e) and 2-(9H-carbazol-9-yl)-N’-[{(4-substitutedphenyl)(piperazin-1-yl)} methyl] aceto hydrazide (6a-6e) were synthesized. All the synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, MASS spectrometry and elemental analysis and also screened for their in vitro anticancer activity against human breast cancer cell line (MCF 7) by sulphorodamine B (SRB) assay method. GI₅₀ was measured by using 10, 20, 40 and 80 µg/ml concentrations of tested compounds along with the standard i.e. Adriamycin. Results revealed that the tested compounds 3a, 3d, 6c, 6d and 6e were comparable to Adriamycin having GI₅₀<10µg/ml. Compound 3a and 6c were found to be most active among all the tested compounds