Journal of Medicinal Chemistry p. 2281 - 2286 (1991)
Update date:2022-08-31
Topics:
Kunz
Iyengar
Dorr
Alberts
Remers
A set of 30 mitomycin C and mitomycin A analogues, including five new compounds, was screened against three different solid human tumor cell lines using the MTT tetrazolium dye assay. A statistically significant correlation among antitumor activity, quinone reduction potential (E( 1/2 ), and the logarithm of the partition coefficient (log P) was obtained, with the most easily reduced and the most lipophilic compounds being the most potent. When these analogues were separated into mitomycin C and mitomycin A subsets, the former gave a correlation only with E( 1/2 ), whereas the latter (which differ little in their E( 1/2 ) values) gave a correlation only with log P. These correlations are in contrast to those made in the P388 leukemia assay in mice wherein the most active mitomycin C and mitomycin A analogues were the most hydrophilic ones. When the same compounds were tested against P388 leukemia cells in the MTT assay, the results were the same as those of the solid tumor assays. Thus, the substantial differences in relative potencies of mitomycins are related not to the kind of tumor cell, but to the type of assay performed, cell culture versus whole animal. No correlation was found between antitumor potency in the cell culture systems and calculated relative DNA binding strengths, probably because the limiting factors in antitumor potency of mitomycins appear to be tumor cell uptake (log P) and/or bioreductive activation (E( 1/2 ).
View Moreshanghai jiuling chemical co.,ltd.
Contact:+86-21-50387295
Address:Zaozhuang Road, Pudong, Shanghai City. China
Hunan Haili Chemical Industry Co.,Ltd.
Contact:+86-731-85521860
Address:No.251, 2nd Section, Furong Road, Changsha,Hunan,China
Contact:+86-22-83718541
Address:32th Floor, Rongqiao Center Intersection of Changjiang Road and Nankai Six Road Nankai District Tianjin 300102, China
zhenjiang runjing high purity chemical co ltd
Contact:+86-511-83361155
Address:No.8.haixi road,international chemical park
WUXI HONOR SHINE CHEMICAL CO.,LTD
Contact:+86-510-83593312
Address:No.1699 Huishan avenue,Huishan district,Wuxi ,Jiangsu,China,214177.(Wuxi Huishan Ecomonic Develop Zone )
Doi:10.1021/jo00398a074
(1978)Doi:10.1007/BF01518047
(1913)Doi:10.1016/S0040-4039(00)96274-9
(1987)Doi:10.1016/S0040-4039(02)01750-1
(2002)Doi:10.1002/cctc.202001553
(2021)Doi:10.1039/c3ce41072b
(2013)