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Design, synthesis and cytotoxic evaluation of nitric oxide‐releasing derivatives of isosteviol
Author(s) -
Liu Yan,
Wang Tingting,
Ling Yong,
Bao Na,
Shi Wei,
Chen Li,
Sun Jianbo
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12956
Subject(s) - furoxan , cytotoxic t cell , ic50 , nitric oxide , chemistry , sunitinib , potency , cell culture , stereochemistry , cytotoxicity , pharmacology , biochemistry , in vitro , cancer , biology , medicine , organic chemistry , genetics
Twenty‐six novel isosteviol derivatives coupled with two types of nitric oxide ( NO ) donors (furoxans and NONO ates) were synthesized and screened for cytotoxic activities against four human cancer cell lines with sunitinib as the positive control. The results showed that seven furoxan‐based derivatives ( 8a , 8b , 8c , 8d , 8e , 9e , and 9f ) exhibited desirable cytotoxic activities, while NONO ate‐based derivatives displayed poor potency because of unstability. Compared with sunitinib, compounds 8a and 8e were more active on all tested cell lines, especially in HCT 116 ( 8a , IC 50 = 0.48 ± 0.02 μ m ; 8e , IC 50 = 0.94 ± 0.01 μ m ); compounds 8b and 8d were more potent on HCT 116 ( IC 50 = 3.39 ± 0.06 and 3.29 ± 0.03 μ m ), HepG2 ( IC 50 = 1.05 ± 0.03 and 5.37 ± 0.08 μ m ), and SW 620 ( IC 50 = 1.33 ± 0.02 and 4.11 ± 0.05 μ m ) cell lines, and 8c exhibited higher activities on HepG2 cells with an IC 50 = 4.76 ± 0.14 μ m . NO ‐releasing experiment of compounds 8a – e , 17a , 18a , 19a , and 21a reminded us that NO ‐releasing amount of this series of isosteviol derivatives positively correlates with their cytotoxic activities.