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

Domenico Iacopetta, Alessia Catalano, Jessica Ceramella, Alexia Barbarossa, Alessia Carocci, Alessia Fazio, Chiara La Torre, Anna Caruso, Marco Ponassi, Camillo Rosano, Carlo Franchini, Maria Stefania Sinicropi

Research output: Contribution to journalArticlepeer-review

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 (IC50 = 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.

Original languageEnglish
Article number104440
JournalBioorganic Chemistry
Volume105
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Anticancers
  • Antioxidants
  • Indole derivatives
  • Molecular docking studies
  • Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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