Mechanochemical synthesis of indolyl chalcones with antiproliferative activity

ABSTRACT

An efficient eco-friendly one-step mechanochemical synthesis of indole hybrid chalcones via the Claisen–Schmidt condensation of 1-methylindole-3-carboxaldehyde with various substituted acetophenones is described using liquid assisted grinding in a high-energy ball mill. The notable advantages of the present method are small organic solvent required (100 μL ethanol) and mainly shorter reaction time (15–60 min) as compared to the conventional method. Antiproliferative activity of synthesized chalcones was studied on several human cancer cell lines (MCF-7, HeLa, A549, MDA-MB-231, HCT116) and non-cancer lines (Cos-7 or BJ-5ta). 3,4,5-Trimethoxyphenyl 3g, 2,5-dimethoxyphenyl 3h, and 2,4,5-trimethylphenyl 3j chalcones showed considerable cytotoxicity, particularly, chalcones 3h and 3j were identified as the most potent and selective anticancer agents with IC₅₀ values 7.9 and 6.6 μM, respectively, against the colon cancer HCT116 cell line.

GRAPHICAL ABSTRACT

KEYWORDS:

• Mechanochemistry
• indolyl chalcones
• antiproliferative activity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The financial support of the Slovak Research and Development Agency under contract No. APVV-18-0357 and that of The Ministry of Education, Science, Research and Sport of the Slovak Republic Grant Agency (project 2/0112/22) are gratefully acknowledged. The support of COST Action CA18112 MechSustInd (www.mechsustind.eu), supported by the COST Association (European Cooperation in Science and Technology, www.cost.eu) is also acknowledged.