title: Synthesis, structure activity relationship and mode of action of 3-substitutedphenyl-1-(2,2,8,8-tetramethyl-3,4,9,10-tetrahydro-2H,8H-pyrano[2,3-f]chromen-6-yl)-propenones as novel anticancer agents in human leukaemia HL-60 cells.
abstract: A novel class of 3-substitutedphenyl-1-(2,2,8,8-tetramethyl-3,4,9,10-tetrahydro-2H,8H-pyrano[2,3-f]chromen-6-yl)-propenones were designed, synthesized and evaluated for their antiproliferative activity against the human cancer cell lines of diverse origin. Structure activity relationship was elucidated with various substitutions on the benzene ring and these variations significantly affected the potency. Most of the twelve tested compounds inhibited the growth of aggressive cancer cell lines. Moreover, three compounds 4j, 4k and 4l displayed excellent cytotoxic profile by inhibiting >90% cell proliferation in HL-60 and Caco-2 cells at 50 μM concentration. Further studies to elucidate the mode of action revealed that these three compounds induced G0/G1 cell cycle arrest and apoptosis, which was accompanied by loss of mitochondrial membrane potential, DNA fragmentation and nuclear morphology in HL-60 cells.
authors: Dept. of Organic Chemistry, Andhra University, Visakhapatnam 530003, India. murthyyln@gmail.com
authors: Y L N
authors: YL
authors: Murthy
authors: K P
authors: KP
authors: Suhasini
authors: A S
authors: AS
authors: Pathania
authors: S
authors: S
authors: Bhushan
authors: Y
authors: Y
authors: Nagendra Sastry
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D047188:Chalcones