Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives
| Autor: | Siniša Radulović, Jasmina Brborić, Jelena Rupar, Vladimir Dobričić, Olivera Čudina, Janez Ilaš, Mara M. Aleksić, Žiga Skok, Jelena Grahovac |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cytotoxicity Pharmaceutical Science 01 natural sciences Biochemistry 03 medical and health sciences A549 Drug Discovery medicine MTT assay Amsacrine Pharmacology A549 cell chemistry.chemical_classification 030102 biochemistry & molecular biology biology 010405 organic chemistry Chemistry Topoisomerase Organic Chemistry Cell cycle Molecular biology 0104 chemical sciences 3. Good health Amino acid anticancer activity acridine derivatives Cell culture biology.protein Molecular Medicine K562 9 acridinyl amino acid derivatives medicine.drug |
| Zdroj: | RSC Med Chem RSC Medicinal Chemistry |
| ISSN: | 2632-8682 |
| Popis: | A series of eleven 9-acridinyl amino acid derivatives were synthesized using a two-step procedure. Cytotoxicity was tested on the K562 and A549 cancer cell lines and normal diploid cell line MRC5 using the MTT assay. Compounds 6, 7, 8 and 9 were the most active, with IC50 values comparable to or lower than that of chemotherapeutic agent amsacrine. 8 and 9 were especially effective in the A549 cell line (IC50 ≈ 6 μM), which is of special interest since amsacrine is not sufficiently active in lung cancer patients. Cell cycle analysis revealed that 7 and 9 caused G2/M block, amsacrine caused arrest in the S phase, while 6 and 8 induced apoptotic cell death independently of the cell cycle regulation. In comparison to amsacrine, 6, 7, 8, and 9 showed similar inhibitory potential towards topoisomerase II, whereas only 7 showed DNA intercalation properties. In contrast to amsacrine, 6, 7, 8 and 9 showed a lack of toxicity towards unstimulated normal human leucocytes. |
| Databáze: | OpenAIRE |
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