Novel 1,3,4-thiadiazole-chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies
Samo za registrovane korisnike
2018
Autori
Jakovljević, KatarinaJoksović, Milan D.
Matić, Ivana Z.
Petrović, Nina
Stanojković, Tatjana
Sladić, Dušan
Vujčić, Miroslava
Janović, Barbara
Joksović, Ljubinka
Trifunović, Snežana S.
Marković, Violeta
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Hybrid compounds that combine the 1,3,4-thiadiazole-containing catechol moiety with a chalcone motif were synthesized and examined for their antioxidant activity, cytotoxicity, and DNA-binding activity. A series of thirteen compounds showed strong antioxidant and cytotoxic effects on human acute promyelocytic leukemia HL-60 cells. Several compounds exerted good cytotoxic activities on cervical adenocarcinoma HeLa cells. The treatment of HeLa cells with IC50 and double IC50 concentrations of the compounds 5a, 5c, 5f, and 5m induced a statistically significant increase in the percentage of cells within a subG1 cell cycle phase. The examined compounds caused G2/M cell cycle arrest in HeLa cells. Each of these compounds triggered apoptosis in HeLa cells through activation of caspase-3, the main effector caspase, caspase-8, which is involved in the extrinsic apoptotic pathway, and caspase-9, which is involved in the intrinsic apoptotic pathway. All of the examined compounds decreased the ex...pression levels of MMP2 in HeLa cells and levels of protumorigenic miR-133b. Compounds 5a and 5m lowered the expression level of oncogenic miR-21 in HeLa cells. In addition, compounds 5a, 5f, and 5m decreased the expression levels of oncogenic miR-155 while the treatment of HeLa cells with compounds 5a, 5c, and 5f increased expression of tumor-suppressive miR-206. Observed effects of these compounds on expression levels of four examined miRNAs suggest their prominent cancer-suppressive activity. An investigation by absorption and fluorescence spectroscopy showed more efficient calf thymus DNA binding activity of the compound 5m in comparison to other tested compounds. Results of a pUC19 plasmid cleavage study and comet assay showed DNA damaging activities of compounds 5a and 5c.
Izvor:
MedChemComm, 2018, 9, 10, 1679-1697Izdavač:
- Royal Soc Chemistry, Cambridge
Finansiranje / projekti:
- Sinteza, modelovanje, fizičko-hemijske i biološke osobine organskih jedinjenja i odgovarajućih kompleksa metala (RS-MESTD-Basic Research (BR or ON)-172016)
- Interakcije prirodnih proizvoda, njihovih derivata i kompleksnih jedinjenja sa proteinima i nukleinskim kiselinama (RS-MESTD-Basic Research (BR or ON)-172055)
- Modifikatori biološkog odgovora u fiziološkim i patološkim stanjima (RS-MESTD-Basic Research (BR or ON)-175011)
Napomena:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/2892
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3051
DOI: 10.1039/c8md00316e
ISSN: 2040-2503
WoS: 000448343300009
Scopus: 2-s2.0-85055283028
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Jakovljević, Katarina AU - Joksović, Milan D. AU - Matić, Ivana Z. AU - Petrović, Nina AU - Stanojković, Tatjana AU - Sladić, Dušan AU - Vujčić, Miroslava AU - Janović, Barbara AU - Joksović, Ljubinka AU - Trifunović, Snežana S. AU - Marković, Violeta PY - 2018 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2089 AB - Hybrid compounds that combine the 1,3,4-thiadiazole-containing catechol moiety with a chalcone motif were synthesized and examined for their antioxidant activity, cytotoxicity, and DNA-binding activity. A series of thirteen compounds showed strong antioxidant and cytotoxic effects on human acute promyelocytic leukemia HL-60 cells. Several compounds exerted good cytotoxic activities on cervical adenocarcinoma HeLa cells. The treatment of HeLa cells with IC50 and double IC50 concentrations of the compounds 5a, 5c, 5f, and 5m induced a statistically significant increase in the percentage of cells within a subG1 cell cycle phase. The examined compounds caused G2/M cell cycle arrest in HeLa cells. Each of these compounds triggered apoptosis in HeLa cells through activation of caspase-3, the main effector caspase, caspase-8, which is involved in the extrinsic apoptotic pathway, and caspase-9, which is involved in the intrinsic apoptotic pathway. All of the examined compounds decreased the expression levels of MMP2 in HeLa cells and levels of protumorigenic miR-133b. Compounds 5a and 5m lowered the expression level of oncogenic miR-21 in HeLa cells. In addition, compounds 5a, 5f, and 5m decreased the expression levels of oncogenic miR-155 while the treatment of HeLa cells with compounds 5a, 5c, and 5f increased expression of tumor-suppressive miR-206. Observed effects of these compounds on expression levels of four examined miRNAs suggest their prominent cancer-suppressive activity. An investigation by absorption and fluorescence spectroscopy showed more efficient calf thymus DNA binding activity of the compound 5m in comparison to other tested compounds. Results of a pUC19 plasmid cleavage study and comet assay showed DNA damaging activities of compounds 5a and 5c. PB - Royal Soc Chemistry, Cambridge T2 - MedChemComm T1 - Novel 1,3,4-thiadiazole-chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies VL - 9 IS - 10 SP - 1679 EP - 1697 DO - 10.1039/c8md00316e ER -
@article{ author = "Jakovljević, Katarina and Joksović, Milan D. and Matić, Ivana Z. and Petrović, Nina and Stanojković, Tatjana and Sladić, Dušan and Vujčić, Miroslava and Janović, Barbara and Joksović, Ljubinka and Trifunović, Snežana S. and Marković, Violeta", year = "2018", abstract = "Hybrid compounds that combine the 1,3,4-thiadiazole-containing catechol moiety with a chalcone motif were synthesized and examined for their antioxidant activity, cytotoxicity, and DNA-binding activity. A series of thirteen compounds showed strong antioxidant and cytotoxic effects on human acute promyelocytic leukemia HL-60 cells. Several compounds exerted good cytotoxic activities on cervical adenocarcinoma HeLa cells. The treatment of HeLa cells with IC50 and double IC50 concentrations of the compounds 5a, 5c, 5f, and 5m induced a statistically significant increase in the percentage of cells within a subG1 cell cycle phase. The examined compounds caused G2/M cell cycle arrest in HeLa cells. Each of these compounds triggered apoptosis in HeLa cells through activation of caspase-3, the main effector caspase, caspase-8, which is involved in the extrinsic apoptotic pathway, and caspase-9, which is involved in the intrinsic apoptotic pathway. All of the examined compounds decreased the expression levels of MMP2 in HeLa cells and levels of protumorigenic miR-133b. Compounds 5a and 5m lowered the expression level of oncogenic miR-21 in HeLa cells. In addition, compounds 5a, 5f, and 5m decreased the expression levels of oncogenic miR-155 while the treatment of HeLa cells with compounds 5a, 5c, and 5f increased expression of tumor-suppressive miR-206. Observed effects of these compounds on expression levels of four examined miRNAs suggest their prominent cancer-suppressive activity. An investigation by absorption and fluorescence spectroscopy showed more efficient calf thymus DNA binding activity of the compound 5m in comparison to other tested compounds. Results of a pUC19 plasmid cleavage study and comet assay showed DNA damaging activities of compounds 5a and 5c.", publisher = "Royal Soc Chemistry, Cambridge", journal = "MedChemComm", title = "Novel 1,3,4-thiadiazole-chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies", volume = "9", number = "10", pages = "1679-1697", doi = "10.1039/c8md00316e" }
Jakovljević, K., Joksović, M. D., Matić, I. Z., Petrović, N., Stanojković, T., Sladić, D., Vujčić, M., Janović, B., Joksović, L., Trifunović, S. S.,& Marković, V.. (2018). Novel 1,3,4-thiadiazole-chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies. in MedChemComm Royal Soc Chemistry, Cambridge., 9(10), 1679-1697. https://doi.org/10.1039/c8md00316e
Jakovljević K, Joksović MD, Matić IZ, Petrović N, Stanojković T, Sladić D, Vujčić M, Janović B, Joksović L, Trifunović SS, Marković V. Novel 1,3,4-thiadiazole-chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies. in MedChemComm. 2018;9(10):1679-1697. doi:10.1039/c8md00316e .
Jakovljević, Katarina, Joksović, Milan D., Matić, Ivana Z., Petrović, Nina, Stanojković, Tatjana, Sladić, Dušan, Vujčić, Miroslava, Janović, Barbara, Joksović, Ljubinka, Trifunović, Snežana S., Marković, Violeta, "Novel 1,3,4-thiadiazole-chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies" in MedChemComm, 9, no. 10 (2018):1679-1697, https://doi.org/10.1039/c8md00316e . .