Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids : current recommendations and future perspectives

Poje, Goran (avtor), Šakić, Davor (avtor), Marinovich, Marina (avtor), You, Jiangyang (avtor), Tarpley, Michael (avtor), Williams, Kevin P. (avtor), Golub, Nikolina (avtor), Dernovšek, Jaka (avtor), Tomašič, Tihomir (avtor), Bešić, Erim (avtor), Rajić, Zrinka (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: harmine, β-carboline, ferrocene, hybrid compounds, antiproliferative activity, glioblastoma multiforme, Hsp90, DYRK1A, antioxidant activity, EPR spectroscopy
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: Str. 595-612
• Številčenje: Vol. 74, iss. 4
• PID: 20.500.12556/RUL-166656
• UDK: 616-006.48
• ISSN pri članku: 1846-9558
• DOI: 10.2478/acph-2024-0033
• COBISS.SI-ID: 206354179
• Datum objave v RUL: 21.01.2025

Gradivo je del revije

• Naslov: Acta pharmaceutica
• Skrajšan naslov: Acta pharm.
• Založnik: Croatian Pharmaceutical Society
• ISSN: 1846-9558
• COBISS.SI-ID: 3817585

Licence

• Licenca: CC BY-ND 4.0, Creative Commons Priznanje avtorstva-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nd/4.0/deed.sl
• Opis: Licenca Creative Commons Brez predelav dovoljuje uporabnikom ponovno distribucijo dela, vendar ne v spremenjeni obliki. Zahtevana je navedba avtorstva.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: harmin, β-karbolin, ferocen, hibridne spojine, antiproliferativno delovanje, multiformni glioblastom, Hsp90, DYRK1A, antioksidativna aktivnost, EPR spektroskopija, glioblastom