Tubulin inhibitory activity of a novel colchicine-binding compounds based on a dinaphthospiropyranran scaffold.
Bioorg Med Chem
; 29: 115874, 2021 01 01.
Article
em En
| MEDLINE
| ID: mdl-33223461
ABSTRACT
Spiropyrans have been investigated for their thermo- and photochromic characteristics, but their biotherapeutic properties have not been addressed. We report anti-proliferative properties of a novel dinaphthospiropyran analogue (1). The compound 1 was synthesized by a simple and expedient method using a one-pot acid-catalyzed aldol condensation of 2-hydroxy-1-naphthaldehyde with 4-piperidone followed by an acetalization reaction. Compound 1 was submitted to anticancer drug screen in the National Cancer Institute's panel of 60 human tumor cell lines. The average concentration of 1 to inhibit 50% cell growth was 5.4 ± 0.23 µM. All cell lines responded at almost the same concentration, suggesting that the action of 1 is not selective for cancer of origin. COMPARE analysis of dose-response data revealed interaction with tubulin as the possible mechanism of action of 1. At molecular level, 1 induced tubulin reorganization in colon cancer HCT-116 cells. Under cell-free conditions, the efficacy of 1 to inhibit tubulin polymerization was comparable to that of paclitaxel and vinblastine. Molecular docking showed that compound 1 binds to the colchicine-binding site of tubulin. We conclude that dinaphthospiropyrans present a novel scaffold for the development of tubulin inhibitors.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tubulina (Proteína)
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Benzopiranos
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Colchicina
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Moduladores de Tubulina
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Indóis
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Antineoplásicos
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Nitrocompostos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article