Fragment-type 4-azolylcoumarin derivatives with anticancer properties
Creators
- 1. Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
- 2. Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia
- 3. Laboratory for Eco-Biotechnology and Drug Development, Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
Description
Several coumarin derivatives with a directly attached azole substituent at C‐4 were synthesized and biologically studied for their anticancer properties. The cell lines used for this investigation (HeLa, K‐562, MDA‐MB‐53, and MCF‐7) demonstrated different sensitivities. The best response in the MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐ 2,5‐diphenyl‐2H‐tetrazolium bromide) assay was shown by K‐562 cells, with compounds displaying activity (3c, IC50 3.06 μM; 4a, IC50 5.24 μM; 4c, IC50 4.7 μM) similar to that of cisplatin (IC50 ~6 μM), which was used as the standard. The studied azole‐substituted coumarins demonstrated weaker activity toward other cell lines, except for compound 4c, which was equally potent in the case of MCF‐7 cells. Additional biological evaluations supported interference with the cell cycle as a potential mechanism of action and confirmed the absence of toxicity in zebrafish embryos. On the basis of these initial results, 4‐azole coumarins should be explored further. Although their activity would need additional optimization, the fact that these compounds are fragment‐like structures with MW <300 and clog P <3 offers enough flexibility to fine‐tune their drug‐like properties
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Related works
- Is derived from
- https://onlinelibrary.wiley.com/doi/10.1002/ardp.202100238 (URL)
- Is identical to
- 34374111 (PMID)
- Is part of
- 0365-6233 (ISSN)
- 1521-4184 (ISSN)