Synthesis, biological evaluation and molecular docking of benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives as novel tubulin polymerization inhibitors.
Bioorg Med Chem
; 27(3): 502-515, 2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30606674
ABSTRACT
Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-five novel benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives were synthesized and evaluated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound 30 showed the most excellent inhibition against tubulin assembly (IC50â¯=â¯1.52⯵M) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50â¯=â¯0.15, 0.21, 0.33 and 0.17⯵M, respectively for A549, Hela, HepG2 and MCF-7). It could also validly induce A549 cell apoptosis, cause cell cycle arrest in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound 30 as a potential anticancer agent.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Sulfonamidas
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Tubulina (Proteína)
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Benzimidazóis
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Moduladores de Tubulina
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Simulação de Acoplamento Molecular
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article