Design, synthesis and cytotoxicity of pyrano[4, 3-b]indol-1(5H)-ones: A hybrid pharmacophore approach via gold catalyzed cyclization. Issue 10 (15th May 2016)

• Record Type: Journal Article
• Authors: Praveen, Chandrasekar; Ananth, D. Babu
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 10(2016)
• Page Start: 2507
• Page End: 2512
• Publication Date: 2016-05-15
• Subjects: Pyranoindolones -- Cycloisomerization -- Gold catalysis -- Cytotoxicity -- Molecular docking; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.087
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Reported herein is the gold(III)-catalyzed 6- endo - dig cycloisomerization of 2-alkynyl-indole-3-carboxylic acids to form pyrano[4, 3- b ]indol-1(5 H )-ones, which are pharmaceutically important structural motifs. The hitherto unknown substrates required for this methodology were conveniently synthesized in five steps with good overall yields. The utility of this new cycloisomerization is demonstrated by the excellent regioselectivity obtained using a range of substrates. The mildness of the method allowed functional group compatibility towards hydroxyl tether, displaying exquisite chemoselectivity. All the synthesized compounds were screened for their tumor cell growth inhibitory activity against human cervix adenocarcinoma (HeLa). Compound7d emerged as the most active (IC50 = 0.69 μM) among the tested series compared to the standard cis -platin (IC50 = 0.08 μM).