4798-70-3Relevant articles and documents
Novel sophoridine derivatives bearing phosphoramide mustard moiety exhibit potent antitumor activities in vitro and in vivo
Li, Dongdong,Dai, Linlin,Zhao, Xiumei,Zhi, Shuang,Shen, Hongsheng,Yang, Zibo
, (2018)
Novel mustard functionalized sophoridine derivatives were synthesized and evaluated for their cytotoxicity against of a panel of various cancer cell lines. They were shown to be more sensitive to S180 and H22 tumor cells with IC50 values ranging from 1.01–3.65 μM, and distinctly were more cytotoxic to cancer cells than normal cell L929. In addition, compounds 7a, 7c, and 7e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Furthermore, they arrested tumor cells in the G1 phase and induced cellular apoptosis. Their potential binding modes with DNA-Top I complex have also been investigated.
Synthesis, cytotoxicity, topoisomerase I inhibition and molecular docking of novel phosphoramide mustard sophoridinic acid analogues
Liu, Kai,Li, Dong-Dong,Zhao, Xiu-Mei,Dai, Lin-Lin,Zhang, Ting,Tao, Zun-Wei
, (2017/02/05)
A series of novel phosphoramide mustard sophoridinic acid analogues, consisting of nitrogen mustard group and sophoridinic acid scaffold, have been designed, synthesized and evaluated for their topoisomerase inhibitory activity as well as cytotoxicity against six tumor cell lines (SMMC-7721, LoVo, MCF-7, K562, S180 and H22) and a normal cell line (L929). Among the compounds tested, five were found to be potent inhibitors and exhibited potent cytotoxicity against S180 and H22 cell lines with IC50 values of 1–4?μM. Further mechanistic studies showed that this class of compounds acted as novel topoisomerase I (Topo I) catalytic inhibitors by preventing the binding of Topo I to DNA and inhibiting the cleavage of DNA, and molecular docking studies revealed that the binding energy for these compounds was comparable to that for classic Topo I inhibitors CPT and HCPT, indicating that the compounds have an interaction with DNA and Topo I.
Protease-mediated enzymatic hydrolysis and activation of aryl phosphoramidate derivatives of stavudine
Venkatachalam,Samuel,Qazi,Uckun
, p. 452 - 466 (2007/10/03)
Several proteases are capable of hydrolyzing the aryl substituted phosphoramidate derivatives of stavudine resulting in the formation of the active metabolite, alaninyl d4T monophosphate. Subtilisin Protease A, Subtilisin Griseus, Subtilisin Carlsberg, Papaya, Bacillus were amongst the most effective proteases in hydrolyzing stavudine derivatives and specificity of their activity was confirmed using several protease inhibitors to block the hydrolysis of these phosphoramidate derivatives. We found that these proteases exhibit chiral selectivity at the phosphorus center of stavudine derivatives. Our results indicate that cellular proteases may be responsible for the activation of these phosphoramidate derivatives. In addition, we show that the enzymatic hydrolysis takes place at the carboxymethyl ester side chain of these pro-drugs and the direct attack on the phosphorus center by these enzymes does not occur. Finally, we describe a novel activation pathway hitherto unknown for the activation and viral inhibitory characteristic shown by these phosphoramidate derivatives of stavudine.
Lipase-mediated stereoselective hydrolysis of stampidine and other phosphoramidate derivatives of stavudine
Venkatachalam,Samuel,Li,Qazi,Mao,Pendergrass,Uckun
, p. 3371 - 3381 (2007/10/03)
Enzymatic hydrolysis of stampidine and other aryl phosphate derivatives of stavudine were investigated using the Candida Antarctica Type B lipase. Modeling studies and comparison of the hydrolysis rate constants revealed a chiral preference of the lipase
ARYL ESTERS OF N,N-BIS(2-CHLOROETHYL)-N',N'-BIS(METHANESULFONYLOXYETHYL)DIAMIDOPHOSPHORIC ACID
Titarenko, I. P.,Protsenko, L. D.
, p. 2116 - 2121 (2007/10/02)
1.It has been found possible to synthesize phsophorylated derivates of esters of methanesulfonic acid containing chloroethyl amino groups. 2.A study has been made of the reaction betrween the chloanhydrides of aryl esters of N,N-bis(2-chloroethyl)amidopho
