Novel 1,3,4-thiadiazole-chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies
Authors
Jakovljević, KatarinaJoksovic, Milan D.
Matić, Ivana Z.

Petrovic, Nina
Stanojković, Tatjana

Sladić, Dušan

Vujčić, Miroslava

Janović, Barbara

Joksovic, Ljubinka
Trifunović, Snežana

Markovic, Violeta

Article (Accepted Version)

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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.
Source:
Medchemcomm, 2018, 9, 10, 1679-1697Publisher:
- Royal Soc Chemistry, Cambridge
Funding / projects:
- Synthesis, modeling, physicochemical and biological properties of organic compounds and related metal complexes (RS-172016)
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)
- Biological response modifiers in physiological and pathological conditions (RS-175011)
Note:
- This is the peer-reviewed version of the following article: Jakovljević, K.; Joksović, M. D.; Matić, I. Z.; Petrović, N.; Stanojković, T.; Sladić, D.; Vujčić, M.; Janović, B.; Joksović, L.; Trifunović, S.; et al. Novel 1,3,4-Thiadiazole-Chalcone Hybrids Containing Catechol Moiety: Synthesis, Antioxidant Activity, Cytotoxicity and DNA Interaction Studies. MedChemComm 2018, 9 (10), 1679–1697. https://doi.org/10.1039/c8md00316e
- Published version: http://cer.ihtm.bg.ac.rs/handle/123456789/2379
- Supplementary information: https://cer.ihtm.bg.ac.rs/handle/123456789/4534
Related info:
- Version of
https://doi.org/10.1039/c8md00316e - Version of
https://cer.ihtm.bg.ac.rs/handle/123456789/2379 - Referenced by
https://cer.ihtm.bg.ac.rs/handle/123456789/4534
DOI: 10.1039/c8md00316e
ISSN: 2040-2503
PubMed: 30429973
WoS: 000448343300009
Scopus: 2-s2.0-85055283028
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IHTMTY - JOUR AU - Jakovljević, Katarina AU - Joksovic, Milan D. AU - Matić, Ivana Z. AU - Petrovic, Nina AU - Stanojković, Tatjana AU - Sladić, Dušan AU - Vujčić, Miroslava AU - Janović, Barbara AU - Joksovic, Ljubinka AU - Trifunović, Snežana AU - Markovic, Violeta PY - 2018 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2379 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/3136 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 Joksovic, Milan D. and Matić, Ivana Z. and Petrovic, Nina and Stanojković, Tatjana and Sladić, Dušan and Vujčić, Miroslava and Janović, Barbara and Joksovic, Ljubinka and Trifunović, Snežana and Markovic, 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., Joksovic, M. D., Matić, I. Z., Petrovic, N., Stanojković, T., Sladić, D., Vujčić, M., Janović, B., Joksovic, L., Trifunović, S.,& Markovic, 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, Joksovic MD, Matić IZ, Petrovic N, Stanojković T, Sladić D, Vujčić M, Janović B, Joksovic L, Trifunović S, Markovic 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, Joksovic, Milan D., Matić, Ivana Z., Petrovic, Nina, Stanojković, Tatjana, Sladić, Dušan, Vujčić, Miroslava, Janović, Barbara, Joksovic, Ljubinka, Trifunović, Snežana, Markovic, 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 . .