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

• Type: Article in International Scientific Journal
• Date: 2024

Authors

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

Journal

Title: International Journal Of Molecular Sciences

Vol. 25

Final page: 1691

ISSN: 1661-6596

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 20