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.
Medicinal Chemistry
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.
Export Options
About this article
Cite this article as:
Andrad F. Saulo, Campos F.S. Edmar, Teixeira S. Claudia, Bandeira C. Cristiano, Lavorato N. Stefania, Romeiro C. Nelilma, Bertollo M. Caryne, Oliveira C. Monica, Souza-Fagundes M. Elaine and Alves J. Ricardo, Synthesis of Novel 2,3,4-trisubstituted-oxazolidine Derivatives and In Vitro Cytotoxic Evaluation, Medicinal Chemistry 2014; 10 (6) . https://dx.doi.org/10.2174/15734064113096660057
DOI https://dx.doi.org/10.2174/15734064113096660057 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Design, Synthesis and Biological Evaluation of Salicylamide Analogues as Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Letters in Drug Design & Discovery Peptide Phage Display: Opportunities for Development of Personalized Anti-Cancer Strategies
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Potential of Natural Compounds that Regulate the Activity of Protein Kinase C
Current Medicinal Chemistry Plant Mediated Silver Nanoparticles and Mode of Action in Cancer Therapy: A Review
Anti-Cancer Agents in Medicinal Chemistry Farnesyltransferase Inhibitors: A Detailed Chemical View on an Elusive Biological Problem
Current Medicinal Chemistry Antagonists of IAP Proteins: Novel Anti-Tumor Agents
Current Medicinal Chemistry A Review of the Primer Approximation Multiplex PCR (PAMP) Technique for Detecting Large Scale Cancer Genomic Lesions
Current Bioinformatics Medical Therapy and Mucosal Healing
Current Drug Targets Non-Invasive Cell Tracking in Cancer and Cancer Therapy
Current Topics in Medicinal Chemistry Targeting Cell Death and Survival Receptors in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Anticancer Chemodiversity of Ranunculaceae Medicinal Plants: Molecular Mechanisms and Functions
Current Genomics Herbal Nano Formulations: Patent and Regulatory Overview
Applied Clinical Research, Clinical Trials and Regulatory Affairs Potential Drugs Targeting Microglia: Current Knowledge and Future Prospects
CNS & Neurological Disorders - Drug Targets A Sustainable Approach to Bis-Indole Synthesis Using Propylene Carbonate as an Eco-Friendly Solvent
Current Organic Synthesis Editorial
Current Medical Imaging Noscapine and its Analogs as Chemotherapeutic Agent: Current updates
Current Topics in Medicinal Chemistry Autoimmune Diseases in Gastroenterology
Current Pharmaceutical Design Potential Anticancer Agents. I. Synthesis of Isoxazole Moiety Containing Quinazoline Derivatives and Preliminarily in vitro Anticancer Activity
Anti-Cancer Agents in Medicinal Chemistry Expression and Function of Kruppel Like-Factors (KLF) in Carcinogenesis
Current Genomics Bioactive Polyphenols from Grapes and Wine Emphasized with Resveratrol
Current Pharmaceutical Design