title: Synthesis of sulfonylhydrazone- and acylhydrazone-substituted 8-ethoxy-3-nitro-2H-chromenes as potent antiproliferative and apoptosis inducing agents.
abstract: 3-Nitro-2H-chromenes have recently been identified as a novel class of potent antitumor agents. In view of the favorable effects shown by sulfonylhydrazones and acylhydrazones, we designed and synthesized a series of sulfonylhydrazone- and acylhydrazone-substituted 8-ethoxy-3-nitro-2H-chromene derivatives, and evaluated their cell growth inhibition activities against A549, KG-1, A2780, and K562 cells. All the tested compounds exhibited more potent antiproliferative activity than BENC-511 against KG-1 cells. These compounds displayed IC50 values in the nanomolar range against A2780 cells. Compound 7d showed prominent cytotoxicity against K562 cells with an IC50 of 0.11 µM, which was comparable to that of BENC-511. Compound 7d arrested K562 cells at the G1 phase at high concentrations and induced apoptosis in K562 cells. Furthermore, 7d increased the levels of cleaved caspase-3, decreased the expression of bcl-2 and induced the cleavage of poly(ADP-ribose) polymerase in K562 cells. Thus, this study provides the development of a series of novel compounds as effective antitumor agents with apoptotic death ability.
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan, P. R. China.
authors.forename: Datong
authors.initials: D
authors.lastname: Zhang
authors.forename: Yuntong
authors.initials: Y
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhao-Peng
authors.initials: ZP
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D006835:Hydrazones
keywords: 3-Nitro-2H-chromene; Acylhydrazone; Antitumor activity; Apoptosis; Sulfonylhydrazone