title: Iodine catalyzed simple and efficient synthesis of antiproliferative 2-pyridones.
abstract: A simple and efficient method for the selective synthesis of 2-pyrdones from 4H-pyrans using iodine as catalyst and ethanol as solvent was developed. The present method is equally effective for both aromatic and hetero aromatic ring containing 4H-pyrans. The compatibility with various functional groups, mild reaction conditions, high yields and application of inexpensive, readily and easily available iodine as catalyst and formation of 2-pyridones as major products are the advantages of the present procedure. In vitro antiproliferative activity of the final synthesized compounds was evaluated with four different human cancer cell lines (Lung adenocarcinoma-A549, Hepatocarcinoma-HepG2, Breast carcinoma-MCF-7 and Ovarian carcinoma-SKOV3) and normal human lung fibroblast cell line (MRC-5). Compounds 2b showed better inhibition against MCF-7, HepG2 and A549 cell lines (IC50 8.00 ± 0.11, 11.93 ± 0.01 and 15.85 ± 0.04 μM, respectively) as compared with doxorubicin and also 2e showed moderate inhibition against MCF-7, HepG2 (IC50 9.32 ± 0.21 and 20.22 ± 0.01 μM, respectively, cell lines, respectively) as compared with doxorubicin. As many clinically used antiproliferative agents induce apoptosis in cancer cells hence, the 2-pyridone analogues were also tested for their ability to induce apoptosis in MCF-7 cells using the caspases-3 and -9 assays.
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India.
authors.forename: Komuraiah
authors.initials: K
authors.lastname: Buduma
authors.affiliation: Toxicology Unit, Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Chinde
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India.
authors.forename: Niranjana Kumar
authors.initials: NK
authors.lastname: Arigari
authors.affiliation: Toxicology Unit, Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Paramjit
authors.initials: P
authors.lastname: Grover
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India. Electronic address: kvnssrinivas@yahoo.co.in.
authors.forename: K V N S
authors.initials: KV
authors.lastname: Srinivas
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India. Electronic address: koteshkumarj@yahoo.com.
authors.forename: J
authors.initials: J
authors.lastname: Kotesh Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D027081:DNA Gyrase / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007455:Iodine / Q000737:chemistry*; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D011728:Pyridones; D059005:Topoisomerase II Inhibitors; D007455:Iodine; D053148:Caspase 3; D053453:Caspase 9; D027081:DNA Gyrase
keywords: Anticancer activity; Iodine; Pyran; Pyridone; Rearrangement