BP-M345 as a Basis for the Discovery of New Diarylpentanoids with Promising Antimitotic Activity

• Tipo: Artigo em Revista Científica Internacional
• Data: 2024

Autores

Moreira, J (Autor) Outra; Silva, PMA (Autor) Outra; Castro, E (Autor) Outra; Lucilia Saraiva (Autor) FFUP; Pinto, M (Autor) Outra; Bousbaa, H (Autor) Outra; Honorina Cidade (Autor) FFUP

Revista

Título: International Journal Of Molecular Sciences

Vol. 25

Página Final: 1691

ISSN: 1661-6596

Editora: MDPI

Indexação

ISI Web of Knowledge - 0 Citações

Scopus

Outras Informações

ID Authenticus: P-010-01S

DOI: 10.3390/ijms25031691

Abstract (EN): Recently, the diarylpentanoid BP-M345 (5) has been identified as a potent in vitro growth inhibitor of cancer cells, with a GI50 value between 0.17 and 0.45 mu M, showing low toxicity in non-tumor cells. BP-M345 (5) promotes mitotic arrest by interfering with mitotic spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed and synthesized a library of BP-M345 (5) analogs and evaluated the cell growth inhibitory activity of three human cancer cell lines within this library in order to perform structure-activity relationship (SAR) studies and to obtain compounds with improved antimitotic effects. Four compounds (7, 9, 13, and 16) were active, and the growth inhibition effects of compounds 7, 13, and 16 were associated with a pronounced arrest in mitosis. These compounds exhibited a similar or even higher mitotic index than BP-M345 (5), with compound 13 displaying the highest antimitotic activity, associated with the interference with mitotic spindle dynamics, inducing spindle collapse and, consequently, prolonged mitotic arrest, culminating in massive cancer cell death by apoptosis.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 20