Cytotoxic effects of a novel maleimide derivative on epithelial and tumor cells

Author(s)

Ali, Bakat ; Kupa, Leonard D. Kanda ; Heluany, Cintia S. ; Drewes, Carine C. ; Vasconcelos, Stanley N. S. ; Farsky, Sandra H. P. ; Stefani, Helio A.

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 72, p. 199-207, JUN 2017.
• Web of Science Citations: 3

Abstract

Novel N-triazolyl maleimide derivatives were synthesized by azide-alkyne Huisgen cycloaddition (1,3-dipolar cycloaddition) and tested for cytotoxicity against a cell line derived from human melanomas SK-Mel-28 and SK-Mel-103, and human umbilical vein endothelial cell lines (HUVEC). The 4l was chose to be biologically tested due to incorporation of benzyl triazolic to the nitrogen of maleimide has not been tested before, and due the satisfactory yield. The analysis of cell metabolism, using the MTT method, showed that the compound 4l impaired cell metabolism in HUVEC only in high concentration (100 mM). A lower concentration of compound 4l, whether in association or not with paclitaxel, was required to cause toxicity in both SK-Mel-28 and SK-Mel-103 cells in comparison with HUVEC cells. Moreover, the ability of 4l to cause cell death was evaluated by flow cytometry, and the data obtained highlighted the apoptotic action of 4l and paclitaxel co-treatment on Sk-Mel-28 cells only, which corroborated the greater efficacy of maleimide compounds against cancer cells. Together, our data provide promising data on the selectivity of maleimide compounds to cancer cells, and suggest that novel maleimide-substituted compounds may be synthesized and tested on different cancer cell lines, as primary or co-adjuvant agents of cancer cell toxicity. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 13/17960-7 - Functionalization of 3-iodo-(L)-Tyrosine via Suzuki-Miyaura Reaction Using Potassium Organotrifluoroborate salts
• Grantee: Stanley Nunes Siqueira Vasconcelos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/17954-4 - Cyclization reaction of Acetyl- and Ethylpyrrolidin-2-one with Potassium Organotrifluoroborate Salts
• Grantee: Bakhat Ali
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/00424-2 - Synthesis of small libraries using potassium Organotrifluoroborates in Suzuki-Miyaura reactions
• Grantee: Helio Alexandre Stefani
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/19802-1 - Effects of lipid-core nanocapsules with acetyleugenol in melanomas: in vivo and in vitro studies
• Grantee: Carine Cristiane Drewes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/07328-4 - Identification of endogenous pathways for the control of inflammation
• Grantee: Sandra Helena Poliselli Farsky
• Support Opportunities: Research Projects - Thematic Grants