Synthesis and biological evaluation of N, N-dialkylcarboxy coumarin-NO donor conjugates as potential anticancer agents.
Animals
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Coumarins
/ chemistry
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Humans
Mice
Molecular Structure
Nitric Oxide
/ chemistry
Structure-Activity Relationship
Diphenylsulfonylfuroxan
N N-dialkylcarboxy coumarin
NO donor
Triple-negative breast cancer
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 11 2021
15 11 2021
Historique:
received:
26
07
2021
revised:
21
09
2021
accepted:
03
10
2021
pubmed:
10
10
2021
medline:
8
1
2022
entrez:
9
10
2021
Statut:
ppublish
Résumé
A series of nitric oxide (NO) donor furoxan conjugates of N, N-dialkylcarboxy coumarins have been synthesized as potential anticancer agents. The synthesized compounds have been tested for their in vitro antiproliferative activities on various cancer and noncancerous cell lines. The candidate derivatives exhibit selectivity towards cancer cells with excellent activities in low nM to µM concentrations. In vitro mechanistic studies indicate that the candidate compounds generate substantial NO, inhibit colony formation, and cause apoptosis in cancer cells. A preliminary in vivo tolerance study of the lead candidate 10 in mice indicates that it is well-tolerated, evidenced by zero mortality and normal body weight gains in treated mice. Further translation of the lead derivative 10 using MDA-MB-231 based tumor xenograft model shows good tumor growth reduction.
Identifiants
pubmed: 34626786
pii: S0960-894X(21)00638-7
doi: 10.1016/j.bmcl.2021.128411
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Coumarins
0
Nitric Oxide
31C4KY9ESH
coumarin
A4VZ22K1WT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
128411Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.