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Synthesis, anticancer and antioxidant properties of new indole and pyranoindole derivatives.

Authors :
Iacopetta D
Catalano A
Ceramella J
Barbarossa A
Carocci A
Fazio A
La Torre C
Caruso A
Ponassi M
Rosano C
Franchini C
Sinicropi MS
Source :
Bioorganic chemistry [Bioorg Chem] 2020 Dec; Vol. 105, pp. 104440. Date of Electronic Publication: 2020 Oct 27.
Publication Year :
2020

Abstract

The indole scaffold has been recognized, over the years, as a model for the synthesis of compounds with anticancer activity by dint of its substantiated ability to act via multiple mechanisms, which also involves the inhibition of enzymes engaged in DNA replication. In this regard, a new series of indole and pyranoindole derivatives have been prepared, some of which showed good antitumor activity and proved their inhibitory effects on the tubulin target. The anticancer activity of the newly synthesized compounds has been evaluated on breast cancer cell lines, as MCF-7 and MDA-MB231, cervical cancer cells line HeLa and Ishikawa endometrial cancer cell line. Among the compounds under study, 7 exhibited a good antitumor activity on HeLa cell line (IC <subscript>50</subscript>  = 3.6 ± 0.5), leading to cell death by apoptosis due to the inhibition of tubulin polymerization, which demonstrated that the compound can explicate its function in a similar way to Vinblastine, a well-known inhibitor of tubulin polymerization. The data were also confirmed by in silico assays. No cytotoxicity against normal cells has been detected. Furthermore, in order to investigate the antioxidant properties, DPPH and ABTS tests were performed, together with fluorescence assays on 3T3-L1 cells. All our findings taken together led us to consider compound 7 a favourable candidate for the battle against cancer.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1090-2120
Volume :
105
Database :
MEDLINE
Journal :
Bioorganic chemistry
Publication Type :
Academic Journal
Accession number :
33217633
Full Text :
https://doi.org/10.1016/j.bioorg.2020.104440