Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 184, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.111752
Keywords
Chalcones; Antitumor activity; Mitosis; Lipophilicity; Paclitaxel chemosensitivity
Categories
Funding
- FCT (Foundation for Science and Technology) [UID/Multi/04423/2019, PTDC/SAU-PUB/28736/2017, POCI-01-0145-FEDER-028736, PTDC/MAR-B10/4694/2014, POCI-01-0145-FEDER-016790, 3599 PPCDT]
- European Regional Development Fund (ERDF) [PTDC/SAU-PUB/28736/2017, POCI-01-0145-FEDER-028736, PTDC/MAR-B10/4694/2014, POCI-01-0145-FEDER-016790, 3599 PPCDT]
- CESPU, Crl [ComeTarget_CESPU_2017]
- FCT [SFRH/BD/111365/2015, SFRH/BD/135852/2018]
- FCT (Fundacao para a Ciencia e Tecnologia) [SFRH/BD/98105/2013]
- POPH (Programa Operacional Potencial Humano) [SFRH/BD/98105/2013]
- Biotech Health Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences) [PD/00016/2012]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-PUB/28736/2017, SFRH/BD/135852/2018, SFRH/BD/98105/2013] Funding Source: FCT
Ask authors/readers for more resources
This study describes the synthesis of a series of chalcones, including pyrazole and alpha,beta-epoxide derivatives, and evaluation of their cell growth inhibitory activity in three human tumor cell lines, as well as their lipophilicity using liposomes as a biomimetic membrane model. Structure-activity and structure-lipophilicity relationships were established for the synthetized chalcones. From this work, nine chalcones (3, 5, 9, 11, 15-19) showing suitable drug-like lipophilicity with potent growth inhibitory activity were identified, being the growth inhibitory effect of compounds 15-17 associated with a pronounced antimitotic effect. Compounds 15-17 affected spindle assembly and, as a consequence, arrested cells at metaphase in NCI-H460 cells, culminating in cell death. Amongst the compounds tested, compound 15 exhibited the highest antimitotic activity as revealed by mitotic index calculation. Moreover, 15 was able to enhance chemosensitivity of tumor cells to low doses of paclitaxel in NCI-H460 cells. The results indicate that 15 exerts its antiproliferative activity by affecting microtubules and causing cell death subsequently to a mitotic arrest, and thus has the potential for antitumor activity. (C) 2019 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available