2012
DOI: 10.1016/j.bmc.2011.11.043
|View full text |Cite
|
Sign up to set email alerts
|

Synthesis, SAR, and preliminary mechanistic evaluation of novel antiproliferative N6,5′-bis-ureido- and 5′-carbamoyl-N6-ureidoadenosine derivatives

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

0
8
0

Year Published

2012
2012
2023
2023

Publication Types

Select...
7

Relationship

1
6

Authors

Journals

citations
Cited by 12 publications
(8 citation statements)
references
References 52 publications
0
8
0
Order By: Relevance
“…It might be speculated that adenosine derivatives, such as CPA, could serve as antimetabolites of nucleic acid metabolism and thereby disrupt DNA or RNA synthesis. Another conceivable mechanism of the action of adenosine derivatives (CPA, IB-MECA), but also of the adenine-like compounds (BAY60-6583), and even of xanthine derivatives (PSB-36, MSX-2, PSB-10) might be due to kinase inhibition targeting the ATP co-substrate binding site [48][49][50]. However, further studies would be required to elucidate the mechanism of action for each of the compounds.…”
Section: Discussionmentioning
confidence: 99%
“…It might be speculated that adenosine derivatives, such as CPA, could serve as antimetabolites of nucleic acid metabolism and thereby disrupt DNA or RNA synthesis. Another conceivable mechanism of the action of adenosine derivatives (CPA, IB-MECA), but also of the adenine-like compounds (BAY60-6583), and even of xanthine derivatives (PSB-36, MSX-2, PSB-10) might be due to kinase inhibition targeting the ATP co-substrate binding site [48][49][50]. However, further studies would be required to elucidate the mechanism of action for each of the compounds.…”
Section: Discussionmentioning
confidence: 99%
“…It is well accepted that ureidoadenosines such as compound 63 binds to the ATP binding site of the kinase bone morphogenetic protein receptor type‐1B (BMPR1b), and that the dysregulation of BMP signaling is associated with various pathological conditions, including cancers (Herrera et al, 2009; Yoshimatsu et al, 2013). Since silyl ethers can be cleaved to generate hydroxyl groups in the cell's physiological environment, and thus increase drug uptake, a number of silyl‐modified nucleosides have been prepared as prodrugs (Panayides et al, 2016; Shelton, Cutler, Browning, et al, 2012; Shelton, Cutler, Oliveira, et al, 2012; Tronchet et al, 2000). Peterson and coworkers prepared a silyl ether derivative ( 64 ) of compound 63 , which appeared to display potent antiproliferative properties, while the parent compound remains inactive (Shelton, Cutler, Browning, et al, 2012; Shelton, Cutler, Oliveira, et al, 2012).…”
Section: Carbon‐silicon Bioisosteric Replacement In Anticancer Drugs ...mentioning
confidence: 99%
“…Peterson and coworkers prepared a silyl ether derivative ( 64 ) of compound 63 , which appeared to display potent antiproliferative properties, while the parent compound remains inactive (Shelton, Cutler, Browning, et al, 2012; Shelton, Cutler, Oliveira, et al, 2012). This activity was attributed to the inhibition of BMPR1b by 63 , suggesting that 64 acted as a prodrug, with the lipophilic TBS group required to enhance cell penetration, before being cleaved in the cytoplasm of the cancer cell, delivering 63 , which inhibited the BMP signaling cascade (Shelton, Cutler, Browning, et al, 2012; Shelton, Cutler, Oliveira, et al, 2012). A number of other O ‐silyl nucleoside analogs ( 65 – 67 ) with high in vitro cytotoxic and antiproliferative activities have also been reported (Panayides et al, 2016; Tronchet et al, 2000).…”
Section: Carbon‐silicon Bioisosteric Replacement In Anticancer Drugs ...mentioning
confidence: 99%
See 1 more Smart Citation
“…Since silyl ethers can be cleaved to hydroxyl groups in vivo, they can be used in designing prodrugs. , Peterson and co-workers reported the antiproliferative activity of ureidoadenosine derivatives such as compound 128 (Figure ). , It was known that hydroxyl derivative 129 binds to the ATP binding site of the kinase BMPR1b. Dysregulation of BMP (bone morphogenetic protein) signaling is associated with various pathological conditions such as cancer.…”
Section: Silicon Incorporation To Improve the Potencymentioning
confidence: 99%