title: Design, synthesis and cytotoxicity of pyrano[4,3-b]indol-1(5H)-ones: A hybrid pharmacophore approach via gold catalyzed cyclization.
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(5H)-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). Compound 7d emerged as the most active (IC50=0.69μM) among the tested series compared to the standard cis-platin (IC50=0.08μM).
authors.affiliation: Functional Materials Division, CSIR-Central Electrochemical Research Institute (CSIR-CECRI), Karaikudi 630003, Tamil Nadu, India.
authors.forename: Chandrasekar
authors.initials: C
authors.lastname: Praveen
authors.affiliation: Pharmaceutical Analysis Department, EGS Pillay College of Pharmacy, Nagapattinam 611002, Tamil Nadu, India.
authors.forename: D Babu
authors.initials: DB
authors.lastname: Ananth
mesh_terms: D000480:Alkynes / Q000737:chemistry; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D015195:Drug Design; D054640:Dual Specificity Phosphatase 3 / Q000378:metabolism*; D006046:Gold / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D007211:Indoles; C012382:indole-3-carboxylic acid; D006046:Gold; D054640:Dual Specificity Phosphatase 3
keywords: Cycloisomerization; Cytotoxicity; Gold catalysis; Molecular docking; Pyranoindolones