Synthesis and in vitro anticancer activity of new 2-thioxo-oxazolidin-4-one derivatives.
Pharmacol Rep
; 69(4): 633-641, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28511054
ABSTRACT
BACKGROUND:
Oxazolidinones derivatives exhibit different biological properties, including anticancer activity. This work aimed to investigate the anticancer potential of five novel 2-Thioxo-oxazolidin-4-one derivatives.METHODS:
Cytotoxicity assays were performed in human peripheral blood mononuclear cells (PBMCs) from healthy individuals and seven tumor cell lines. Apoptosis detection and cell cycle were evaluated by flow cytometry and the expression of genes involved in cell death processes by Real-Time PCR.RESULTS:
All oxazolinedione derivatives were not cytotoxic in PBMCs. NB-5 showed the best results in cancer cells, inhibiting the growth of all tumor cell lines tested. NB-4 exhibited the highest cytotoxicity in Jurkat cells (IC50=15.19µM) and NB-3 showed better anticancer effects in HL-60 (17.84µM). Only NB-4 significantly induced apoptosis in acute leukemia cells (p=0.001). All compounds caused a significant increase in expression of pro-apoptotic gene BID (p<0.05) and BECN1 (p<0.05). NB-3 significantly modulated the expression of RIPK3 (p=0.02) and DDIT3 (p=0.014), while NB-2 induced an increase of CDKN1A (p=0.03) and NB-4 induced PPARγ gene (p=0.0006).CONCLUSION:
NB-5 showed antitumor effects in solid and hematopoietic cancer cells, while other derivatives produced higher activity against hematopoietic cells. In acute leukemia cells, oxazolidinone derivatives modulated the expression of genes involved in apoptosis, ER stress, necroptosis and inflammation.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Cell Survival
/
Imidazolidines
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Pharmacol Rep
Journal subject:
FARMACOLOGIA
Year:
2017
Type:
Article
Affiliation country:
Brazil