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Synthesis of Sulfonylhydrazone‐ and Acylhydrazone‐Substituted 8‐Ethoxy‐3‐nitro‐2 H ‐chromenes as Potent Antiproliferative and Apoptosis Inducing Agents
Author(s) -
Zhang Datong,
Ma Yuntong,
Liu Yu,
Liu ZhaoPeng
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400082
Subject(s) - cytotoxicity , apoptosis , chemistry , k562 cells , ic50 , stereochemistry , alkoxy group , in vitro , pharmacology , cell growth , cell cycle , poly adp ribose polymerase , biochemistry , polymerase , biology , enzyme , alkyl , organic chemistry
3‐Nitro‐2 H ‐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‐2 H ‐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 IC 50 values in the nanomolar range against A2780 cells. Compound 7d showed prominent cytotoxicity against K562 cells with an IC 50 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.