Microwave Assisted One-Pot Three-Component Synthesis of Novel Pyranocarbazole Derivatives as Antiproliferative Agents and Molecular Docking Studies

Abstract

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-(methylthio)-2-nitroethenamine under microwave irradiation. This transformation presumably occurs via Knoevenagel condensation-Michael addition–tautomerism intramolecular O-cyclization-elimination sequence of reactions creating one C-O bond and two C-C bonds. The significant features of this one-pot reaction include catalyst free, solvent free, atom-economy, no column chromatographic purification, short reaction time and good yield. Further, the synthesized pyranocarbazole derivatives were evaluated for their antiproliferative activity against four cancer cell lines such as DU 145 (prostate cancer), MDA-MB-231 (breast cancer), SKOV3 (ovarian cancer) and B16-F10 (skin cancer). The results clearly demonstrated that trimethoxyphenyl substituted pyrano[3,2-c]carbazole (9h) exhibited most potent antriproliferative activity against tested cell lines. Compounds 9a, 9b and 11a were also displayed pronounced antriproliferative activity. In addition, molecular docking studies revealed that the lead compounds bind to the colchicine binding site of the tubulin effectively.