Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids
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 th...
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2024-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2024-0033 |
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| author | Poje Goran Šakić Davor Marinović Marina You Jiangyang Tarpley Michael Williams Kevin P. Golub Nikolina Dernovšek Jaka Tomašič Tihomir Bešić Erim Rajić Zrinka |
| author_facet | Poje Goran Šakić Davor Marinović Marina You Jiangyang Tarpley Michael Williams Kevin P. Golub Nikolina Dernovšek Jaka Tomašič Tihomir Bešić Erim Rajić Zrinka |
| author_sort | Poje Goran |
| collection | DOAJ |
| description | 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 (IC50 = 3.7 ± 0.1 µmol L–1, SI = 12.6) and ., the C-6 substituted harmicene (IC50 = 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. |
| format | Article |
| id | doaj-art-e734279eb13d41af9cd6166f4dcf3271 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-e734279eb13d41af9cd6166f4dcf32712025-02-02T15:47:25ZengSciendoActa Pharmaceutica1846-95582024-12-0174459561210.2478/acph-2024-0033Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybridsPoje Goran0Šakić Davor1Marinović Marina2You Jiangyang3Tarpley Michael4Williams Kevin P.5Golub Nikolina6Dernovšek Jaka7Tomašič Tihomir8Bešić Erim9Rajić Zrinka10University of Zagreb Faculty of Pharmacy and Biochemistry, 10 000 Zagreb, CroatiaUniversity of Zagreb Faculty of Pharmacy and Biochemistry, 10 000 Zagreb, CroatiaUniversity of Zagreb Faculty of Pharmacy and Biochemistry, 10 000 Zagreb, CroatiaRudjer Bošković Institute, 10 000 Zagreb, CroatiaNorth Carolina Central University Durham, NC 27707, USANorth Carolina Central University Durham, NC 27707, USAUniversity of Zagreb Faculty of Pharmacy and Biochemistry, 10 000 Zagreb, CroatiaUniversity of Ljubljana, Faculty of Pharmacy, 1000 Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Pharmacy, 1000 Ljubljana, SloveniaUniversity of Zagreb Faculty of Pharmacy and Biochemistry, 10 000 Zagreb, CroatiaUniversity of Zagreb Faculty of Pharmacy and Biochemistry, 10 000 Zagreb, CroatiaThe 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 (IC50 = 3.7 ± 0.1 µmol L–1, SI = 12.6) and ., the C-6 substituted harmicene (IC50 = 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.https://doi.org/10.2478/acph-2024-0033harmineβ-carbolineferrocenehybrid compoundsantiproliferative activityglioblastoma multiformehsp90dyrk1aantioxidant activityepr spectroscopy |
| spellingShingle | Poje Goran Šakić Davor Marinović Marina You Jiangyang Tarpley Michael Williams Kevin P. Golub Nikolina Dernovšek Jaka Tomašič Tihomir Bešić Erim Rajić Zrinka Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids Acta Pharmaceutica harmine β-carboline ferrocene hybrid compounds antiproliferative activity glioblastoma multiforme hsp90 dyrk1a antioxidant activity epr spectroscopy |
| title | Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids |
| title_full | Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids |
| title_fullStr | Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids |
| title_full_unstemmed | Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids |
| title_short | Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids |
| title_sort | unveiling the antiglioblastoma potential of harmicens harmine and ferrocene hybrids |
| topic | harmine β-carboline ferrocene hybrid compounds antiproliferative activity glioblastoma multiforme hsp90 dyrk1a antioxidant activity epr spectroscopy |
| url | https://doi.org/10.2478/acph-2024-0033 |
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