TY - JOUR
T1 - Synthesis, anticancer and antioxidant properties of new indole and pyranoindole derivatives
AU - Iacopetta, Domenico
AU - Catalano, Alessia
AU - Ceramella, Jessica
AU - Barbarossa, Alexia
AU - Carocci, Alessia
AU - Fazio, Alessia
AU - La Torre, Chiara
AU - Caruso, Anna
AU - Ponassi, Marco
AU - Rosano, Camillo
AU - Franchini, Carlo
AU - Sinicropi, Maria Stefania
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Anticancers
KW - Antioxidants
KW - Indole derivatives
KW - Molecular docking studies
KW - Tubulin
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U2 - 10.1016/j.bioorg.2020.104440
DO - 10.1016/j.bioorg.2020.104440
M3 - Article
C2 - 33217633
AN - SCOPUS:85096674881
VL - 105
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
SN - 0045-2068
M1 - 104440
ER -