Details

Autor(en) / Beteiligte

• Pinto, Patricia
• Machado, Carmen Mariana
• Moreira, Joana
• Almeida, José Diogo P.
• Silva, Patrícia M.A.
• Henriques, Ana C.
• Soares, José X.
• Salvador, Jorge A.R.
• Afonso, Carlos
• Pinto, Madalena
• Bousbaa, Hassan
• Cidade, Honorina

Titel

Chalcone derivatives targeting mitosis: synthesis, evaluation of antitumor activity and lipophilicity

Ist Teil von

• European journal of medicinal chemistry, 2019-12, Vol.184, p.111752-111752, Article 111752

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• This study describes the synthesis of a series of chalcones, including pyrazole and α,β-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. [Display omitted] •Chalcones 3, 5, 9, 11, and 15–19 displayed potent antiproliferative activity in tumor cell lines.•The antimitotic effect of chalcones 15–17 was investigated.•15 was able to enhance chemosensitivity of tumor cells to paclitaxel.•Lipophilicity was determined and a structure-property relationships were proposed.•3, 5, 9, 11, and 15–19 showed suitable drug-like lipophilicity.