Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives
Само за регистроване кориснике
2020
Аутори
Rupar, JelenaDobričić, Vladimir
Grahovac, Jelena
Radulović, Siniša
Skok, Žiga
Ilaš, Janez
Aleksić, Mara
Brborić, Jasmina
Čudina, Olivera
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Извор:
RSC Medicinal Chemistry, 2020, 11, 3, 378-386Издавач:
- Royal Society of Chemistry
Финансирање / пројекти:
- Развој молекула са антиинфламаторним и кардиопроактивним дејством: структурне модификације, моделовање, физичкохемијска карактеризација и формулациона испитивања (RS-MESTD-Basic Research (BR or ON)-172041)
- Фармакодинамска и фармакогеномска испитивања новијих лекова у лечењу солидних тумора (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41026)
DOI: 10.1039/c9md00597h
ISSN: 2632-8682
WoS: 000526953000005
Scopus: 2-s2.0-85083014447
Институција/група
PharmacyTY - 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 . .