Medicinal Chemistry

Honorary Life Fellow
Kings College
University of Cambridge


Synthesis of Novel 2,3,4-trisubstituted-oxazolidine Derivatives and In Vitro Cytotoxic Evaluation

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: Departamento de Produtos Farmaceuticos, Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Av. Antonio Carlos, 6627, Belo Horizonte, MG 31.270- 901, Brazil.

Graphical 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.

Keywords: Anticancer, apoptosis, chiral, HL60, MDA-MB231, oxazolidine.

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Article Details

Page: [609 - 618]
Pages: 10
DOI: 10.2174/15734064113096660057