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.
TY - JOUR
AU - Rupar, Jelena
AU - Dobričić, Vladimir
AU - Grahovac, Jelena
AU - Radulović, Siniša
AU - Skok, Žiga
AU - Ilaš, Janez
AU - Aleksić, Mara
AU - Brborić, Jasmina
AU - Čudina, Olivera
PY - 2020
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3606
AB - 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.
PB - Royal Society of Chemistry
T2 - RSC Medicinal Chemistry
T1 - Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives
VL - 11
IS - 3
SP - 378
EP - 386
DO - 10.1039/c9md00597h
DO - 2-s2.0-85083014447
ER -
@article{
author = "Rupar, Jelena and Dobričić, Vladimir and Grahovac, Jelena and Radulović, Siniša and Skok, Žiga and Ilaš, Janez and Aleksić, Mara and Brborić, Jasmina and Čudina, Olivera",
year = "2020",
abstract = "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.",
publisher = "Royal Society of Chemistry",
journal = "RSC Medicinal Chemistry",
title = "Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives",
volume = "11",
number = "3",
pages = "378-386",
doi = "10.1039/c9md00597h, 2-s2.0-85083014447"
}
Rupar, J., Dobričić, V., Grahovac, J., Radulović, S., Skok, Ž., Ilaš, J., Aleksić, M., Brborić, J.,& Čudina, O.. (2020). Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives. in RSC Medicinal Chemistry
Royal Society of Chemistry., 11(3), 378-386.
https://doi.org/10.1039/c9md00597h
Rupar J, Dobričić V, Grahovac J, Radulović S, Skok Ž, Ilaš J, Aleksić M, Brborić J, Čudina O. Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives. in RSC Medicinal Chemistry. 2020;11(3):378-386.
doi:10.1039/c9md00597h .
Rupar, Jelena, Dobričić, Vladimir, Grahovac, Jelena, Radulović, Siniša, Skok, Žiga, Ilaš, Janez, Aleksić, Mara, Brborić, Jasmina, Čudina, Olivera, "Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives" in RSC Medicinal Chemistry, 11, no. 3 (2020):378-386,
https://doi.org/10.1039/c9md00597h . .
