Synthesis and Antiproliferative Activity of Novel Pyranocarbazoles

A new series of pyrano[3,2-c] carbazole and pyrano[2,3-a] carbazole derivatives have been synthesized by one-pot three-component coupling of 4-hydroxycarbazole or 2-hydroxycarbazole, aromatic substituted aldehydes, and (E)-N-methyl-1-(methylsulfanyl)-2-nitro-ethenamine under microwave irradiation. This rapid one-pot reaction does not require a catalyst, is solvent-free, avoids chromatographic purification, and provides good yields. The synthesized pyranocarbazole derivatives were evaluated for their antiproliferative activity against four cancer cell lines: DU 145 (prostate cancer), MDA-MB-231 (breast cancer), SKOV3 (ovarian cancer), and B16-F10 (skin cancer). N-Methyl-3-nitro-4-(3,4,5-trimethoxyphenyl)-4,7-dihydropyrano[3,2-c] carbazol-2-amine exhibited the most potent antiproliferative activity against the tested cell lines, while other test compounds showed weak or moderate antiproliferative activity, among them N-methyl-3-nitro-4-phenyl-4,7-dihydropyrano[3,2-c] carbazol-2-amine, 4-(4-fluorophenyl)-N-methyl-3-nitro-4,7-dihydropyrano[3,2-c] carbazol-2-amine, and N-methyl-2-nitro-1-phenyl-1,11-dihydropyrano[3,2-a] carbazol-3-amine displayed IC50 values in the low micromolar range.