Title:Synthesis of Novel 2,3,4-trisubstituted-oxazolidine Derivatives and In Vitro Cytotoxic Evaluation
Volume: 10
Issue: 6
Author(s): Saulo F. Andrad, Edmar F.S. Campos, Claudia S. Teixeira, Cristiano C. Bandeira, Stefania N. Lavorato, Nelilma C. Romeiro, Caryne M. Bertollo, Monica C. Oliveira, Elaine M. Souza-Fagundes and Ricardo J. Alves
Affiliation:
Keywords:
Anticancer, apoptosis, chiral, HL60, MDA-MB231, oxazolidine.
Abstract: We have previously reported the discovery of cytotoxic and pro-apoptotic hit compound 1,1-dimethylethyl (S)-
2,2-dimethyl-4-[(3-nitrophenoxy)methyl]-3-oxazolidinecarboxylate 1 against leukemia cells. In the present work we describe
the synthesis of 25 derivatives of this hit varying the substituent at ring or stereochemistry of the oxazolidine ring
and evaluated them against human cancer cells lines. Six compounds exerted significant activity against HL60 promyelocytic
leukemia cells with IC50 in low micromolar range (4-18 μM) and three compounds displayed activity against
MDA-MB231 breast cancer cells (25-37 μM). In vitro cytotoxicity on normal cells PBMC (human peripheral blood mononuclear
cells) was also evaluated. Compounds 7e (p-NO2, S) and 7m (p-COOCH3, S) showed good antiproliferative activity
against HL60 (4 and 5 μM) and MDA-MB231 (37 and 25 μM) without affecting lymphocyte proliferation in
PBMC, indicating low toxicity to normal cells. Besides, compound 7e induced DNA fragmentation on about 100% of
HL60 cells at 50 μM. In this case, it was more potent than 7m and lead 1. This indicated that compound 7e has a great
pro-apoptotic potential.
