20.500.12556/RUL-166656 Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids current recommendations and future perspectives The poor prognosis of glioblastoma multiforme, inadequate treatment options, and growing drug resistance urge the need to find new effective agents. Due to the significant anti-cancer potential of harmicens, hybrid compounds which comprise harmine/β-carboline and ferrocene moiety, we investigated their antiglioblastoma potential in vitro and mechanism of action (inhibition of DYRK1A, Hsp90, anti-oxidative activity). The results have shown that triazole-type harmicens, namely 5, with a ferrocene moiety in C-3 position of the β-carboline ring (IC$_{50}$ = 3.7 ± 0.1 µmol L$^{–1}$, SI = 12.6) and., the C-6 substituted harmicene (IC$_{50}$ = 7.4 ± 0.5 µmol L$^{–1}$, SI = 5.8) exert remarkable activity and selectivity against human malignant glioblastoma cell line (U251) in vitro. On the other hand, amide-type harmicens 10, 12, and 14 exhibited strong, but non-selective activity, in the low micro-molar range. Mechanistic studies revealed that among active compounds, amide-type harmicens 12 and 14 inhibit DYRK1A and Hsp90 CTD, whereas compound 14 showed pronounced antioxidative activity. Therefore, the antiproliferative activity of harmicens might be a combination of complex molecular interactions. harmine β-carboline ferrocene hybrid compounds antiproliferative activity glioblastoma multiforme Hsp90 DYRK1A antioxidant activity EPR spectroscopy harmin β-karbolin ferocen hibridne spojine antiproliferativno delovanje multiformni glioblastom Hsp90 DYRK1A antioksidativna aktivnost EPR spektroskopija glioblastom true false true Angleški jezik Slovenski jezik Članek v reviji 2025-01-21 08:22:39 2025-01-21 08:22:46 2025-01-22 03:54:02 0000-00-00 00:00:00 2024 0 0 Str. 595-612 iss. 4 Vol. 74 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006.48 1846-9558 10.2478/acph-2024-0033 206354179 Unveiling-the-antiglioblastoma-potential-of-harmicens-harmine-and-ferrocene-hybrids.pdf Unveiling-the-antiglioblastoma-potential-of-harmicens-harmine-and-ferrocene-hybrids.pdf 1 749A62CC5849506021424369F89BB4D7 dd4b0a95003e5f45ac9fc803df833ae9e1ef43a9b25bcde5556122876a896962 407f4da9-d7c9-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=198416 https://sciendo.com/article/10.2478/acph-2024-0033 1 bce84e14-d7c7-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=198415 Fakulteta za farmacijo 0 0 0