Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action
Само за регистроване кориснике
2022
Аутори
Bondžić, Aleksandra M.Žakula, Jelena J.
Korićanac, Lela
Keta, Otilija D.
Janjić, Goran
Đorđević, Ivana S.
Rajković, Snežana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Herein, the stability, lipophilicity, in vitro cytotoxicity, and influence on acetylcholinesterase of five dinuclear platinum(II) complexes with the general formula [{Pt(en)Cl}2(μ-L)]2+ (L is a different aromatic nitrogen-containing heterocyclic bridging ligands pyrazine (pz, Pt1), pyridazine (pydz, Pt2), quinoxaline (qx, Pt3), phthalazine (phtz, Pt4) and quinazoline (qz, Pt5), while en is bidentate coordinated ethylenediamine) were evaluated. The most active analyzed platinum complexes induced time-dependent growth inhibition of A375, HeLa, PANC-1, and MRC-5 cells. The best efficiency was achieved on HeLa and PANC-1 cells for Pt1, Pt2, and Pt3 at the highest concentration, while Pt1 was significantly more potent than cisplatin at a lower concentration. Additionally, a lower effect on normal cells was observed compared to cisplatin, which may indicate potentially fewer side effects of these complexes. Selected complexes induce reactive oxygen species and apoptosis on tumor cell lines. ...The most potent reversible acetylcholinesterase (AChE) inhibitors were Pt2, Pt4, and Pt5. Pt1 showed similar inhibitory potential toward AChE as cisplatin, but a different type of inhibition, which could contribute to lower neurotoxicity. Docking studies revealed that Pt2 and Pt4 were bound to the active gorge above the catalytic triad. In contrast, the other complexes were bound to the edge of the active gorge without impeding the approach to the catalytic triad. According to this, Pt1 represents a promising compound with potent anticancer properties, high selectivity, and low neurotoxicity.
Кључне речи:
Acetylcholinesterase / Cytotoxicity / Docking studies / Neurotoxicity / Platinum(II) complexesИзвор:
Chemico-Biological Interactions, 2022, 351, 109708-Издавач:
- Elsevier
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200017 (Универзитет у Београду, Институт за нуклеарне науке Винча, Београд-Винча) (RS-200017)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200026 (Универзитет у Београду, Институт за хемију, технологију и металургију - ИХТМ) (RS-200026)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200122 (Универзитет у Крагујевцу, Природно-математички факултет) (RS-200122)
DOI: 10.1016/j.cbi.2021.109708
ISSN: 0009-2797; 1872-7786
PubMed: 34666020
WoS: 000820470000001
Scopus: 2-s2.0-85118274093
Институција/група
IHTMTY - JOUR AU - Bondžić, Aleksandra M. AU - Žakula, Jelena J. AU - Korićanac, Lela AU - Keta, Otilija D. AU - Janjić, Goran AU - Đorđević, Ivana S. AU - Rajković, Snežana PY - 2022 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/5412 AB - Herein, the stability, lipophilicity, in vitro cytotoxicity, and influence on acetylcholinesterase of five dinuclear platinum(II) complexes with the general formula [{Pt(en)Cl}2(μ-L)]2+ (L is a different aromatic nitrogen-containing heterocyclic bridging ligands pyrazine (pz, Pt1), pyridazine (pydz, Pt2), quinoxaline (qx, Pt3), phthalazine (phtz, Pt4) and quinazoline (qz, Pt5), while en is bidentate coordinated ethylenediamine) were evaluated. The most active analyzed platinum complexes induced time-dependent growth inhibition of A375, HeLa, PANC-1, and MRC-5 cells. The best efficiency was achieved on HeLa and PANC-1 cells for Pt1, Pt2, and Pt3 at the highest concentration, while Pt1 was significantly more potent than cisplatin at a lower concentration. Additionally, a lower effect on normal cells was observed compared to cisplatin, which may indicate potentially fewer side effects of these complexes. Selected complexes induce reactive oxygen species and apoptosis on tumor cell lines. The most potent reversible acetylcholinesterase (AChE) inhibitors were Pt2, Pt4, and Pt5. Pt1 showed similar inhibitory potential toward AChE as cisplatin, but a different type of inhibition, which could contribute to lower neurotoxicity. Docking studies revealed that Pt2 and Pt4 were bound to the active gorge above the catalytic triad. In contrast, the other complexes were bound to the edge of the active gorge without impeding the approach to the catalytic triad. According to this, Pt1 represents a promising compound with potent anticancer properties, high selectivity, and low neurotoxicity. PB - Elsevier T2 - Chemico-Biological Interactions T1 - Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action VL - 351 SP - 109708 DO - 10.1016/j.cbi.2021.109708 ER -
@article{ author = "Bondžić, Aleksandra M. and Žakula, Jelena J. and Korićanac, Lela and Keta, Otilija D. and Janjić, Goran and Đorđević, Ivana S. and Rajković, Snežana", year = "2022", abstract = "Herein, the stability, lipophilicity, in vitro cytotoxicity, and influence on acetylcholinesterase of five dinuclear platinum(II) complexes with the general formula [{Pt(en)Cl}2(μ-L)]2+ (L is a different aromatic nitrogen-containing heterocyclic bridging ligands pyrazine (pz, Pt1), pyridazine (pydz, Pt2), quinoxaline (qx, Pt3), phthalazine (phtz, Pt4) and quinazoline (qz, Pt5), while en is bidentate coordinated ethylenediamine) were evaluated. The most active analyzed platinum complexes induced time-dependent growth inhibition of A375, HeLa, PANC-1, and MRC-5 cells. The best efficiency was achieved on HeLa and PANC-1 cells for Pt1, Pt2, and Pt3 at the highest concentration, while Pt1 was significantly more potent than cisplatin at a lower concentration. Additionally, a lower effect on normal cells was observed compared to cisplatin, which may indicate potentially fewer side effects of these complexes. Selected complexes induce reactive oxygen species and apoptosis on tumor cell lines. The most potent reversible acetylcholinesterase (AChE) inhibitors were Pt2, Pt4, and Pt5. Pt1 showed similar inhibitory potential toward AChE as cisplatin, but a different type of inhibition, which could contribute to lower neurotoxicity. Docking studies revealed that Pt2 and Pt4 were bound to the active gorge above the catalytic triad. In contrast, the other complexes were bound to the edge of the active gorge without impeding the approach to the catalytic triad. According to this, Pt1 represents a promising compound with potent anticancer properties, high selectivity, and low neurotoxicity.", publisher = "Elsevier", journal = "Chemico-Biological Interactions", title = "Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action", volume = "351", pages = "109708", doi = "10.1016/j.cbi.2021.109708" }
Bondžić, A. M., Žakula, J. J., Korićanac, L., Keta, O. D., Janjić, G., Đorđević, I. S.,& Rajković, S.. (2022). Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action. in Chemico-Biological Interactions Elsevier., 351, 109708. https://doi.org/10.1016/j.cbi.2021.109708
Bondžić AM, Žakula JJ, Korićanac L, Keta OD, Janjić G, Đorđević IS, Rajković S. Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action. in Chemico-Biological Interactions. 2022;351:109708. doi:10.1016/j.cbi.2021.109708 .
Bondžić, Aleksandra M., Žakula, Jelena J., Korićanac, Lela, Keta, Otilija D., Janjić, Goran, Đorđević, Ivana S., Rajković, Snežana, "Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action" in Chemico-Biological Interactions, 351 (2022):109708, https://doi.org/10.1016/j.cbi.2021.109708 . .