Journal of Pharmaceutical Sciences p. 57 - 62 (1990)
Update date:2022-08-03
Topics:
Kang
Spears
A variety of organoselenium alkylating agents were synthesized, using 2-hydroxyethyl and 3-hydroxypropyl selenocyanate intermediates, and studied to determine their chemical reactivities with 4-(4-nitrobenzyl) pyridine (NBP) and cytotoxicities against CCRF-CEM, L1210/0, and L1210/L-PAM cells. The comparison between the 2-chloroethyl sulfides and selenides 1-4 revealed the markedly enhanced nucleophilicity of selenium (Se) over sulfur (S) by two or more orders of magnitude. This finding indicates that a major consideration in the design of antitumor alkylating organoselenides is the reactivity of selenium. A Taft plot of the experimental first-order rate constant, k'(nbp), and σ* in a series of 2-chloroethylseleno compounds gave a slope of -1.73 (ρ*), with the exception of 2-chloroethyl 2-nitrophenyl selenide (10). The anomalous behavior of 10 is explained in terms of the ortho-nitro stabilization effect directly interacting with the selenium atom of ethyleneselenonium ion to form a 5-membered cyclic intermediate. In the same series, a 5000-fold difference in alkylating reactivity offered only a sixfold variation in cytotoxicity against CCRF-CEM cells. Increasing the alkylating chain length from ethylene to propylene units markedly reduced alkylating reactivities. In the CH3Se(CH2)(n)Cl series, 16 (n = 3) was 1.5 x 105 times slower than 2 (n = 2) in NBP alkylation, revealing that 3-chloro-n-propyl selenides are not chemically reactive enough to be biological alkylating agents despite the presence of the highly nucleophilic selenium atom. Replacement of chloride with mesylate in 3-substituted propyl selenides, such as 17 and 20, restored desirable reactivities and cytotoxicities.
View MoreShiJiaZhuang Dowell Chemical Co.,Ltd.
website:http://www.dowechem.com
Contact:+86-13463963265
Address:Xiyangling village, high tech Zone, Shijiazhuang,Hebei, China
zhenjiang runjing high purity chemical co ltd
Contact:+86-511-83361155
Address:No.8.haixi road,international chemical park
Contact:86+21-56421993
Address:3F,BUILDING 10,NO.2889 JINKE ROAD, SHANGHAI.
Shanghai Maxchemco Chemical Industry Co., Ltd.
Contact:(86)21-51079223
Address:No.1305-8, B241, the Ecust Park, Huajing Road, Xuhui District, Shanghai
Chengdu Chengnuo New-Tech Co., Ltd
Contact:0086-028-85749078
Address:4 Jiuyang road,Jiulong industrial port,Chengdu, China
Doi:10.1039/c6cc06399c
(2016)Doi:10.1002/cbic.201000526
(2011)Doi:10.1039/c7pp00166e
(2017)Doi:10.1002/cmdc.202100013
(2021)Doi:10.1002/ejic.201402793
(2014)Doi:10.1002/aoc.3604
(2017)