RNA-targeting low-molecular-weight fluorophores for nucleoli staining: synthesis, in silico modelling and cellular imaging
Nema prikaza
Autori
Kurutos, AtanasNikodinović-Runić, Jasmina
Veselinović, Aleksandar
Veselinović, Jovana B.
Kamounah, Fadhil S.
Ilić-Tomić, Tatjana
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Herein we present our work on the synthesis, investigation of the photophysical properties, interactions with nucleic acids, molecular docking, and imaging application of three carbocyanine dyes. The described low-molecular-weight compounds were found to exhibit high resistance against photobleaching and showed promising optical properties as fluorescent labeling agents for ribonucleic acids. They form strong biocomplexes (log K-s = 6.11-7.84) and revealed remarkable sensitivity towards RNA, reaching up to a 379 times increase of the emission signal when bound to AU-rich sequences. According to the score values obtained from the molecular docking studies, the compounds show strong binding affinity towards RNA macromolecules. All fluorophores exhibit significant cell tolerance since they were found to be 16 to 60 times less toxic against MRC5 cells (healthy human fibroblasts) compared to the conventional Thiazole Orange - TO. The IC50 concentrations for the compounds were calculated up ...to 40 mu M in human fibroblasts MRC5, A549 adenocarcinomic human alveolar basal epithelial cells, the HCT116 human colon cancer cell line, and MDA-MB-231 adenocarcinoma cells. Analyzing the dyes for preferential cytotoxicity towards cancer cell lines in comparison to the normal human fibroblasts, we found a candidate exhibiting promising anticancer potential. Based on the selectivity (Si) towards cancer cells and more specifically against difficult to treat colon HCT116 carcinoma, we can suggest these small molecules as an interesting platform for further development. We have also demonstrated the efficiency of the carbocyanines as staining agents for in vivo labeling of human cells as well as microbial and eukaryotic cells.
Izvor:
New Journal of Chemistry, 2021, 45, 29, 12818-12829Izdavač:
- Royal Soc Chemistry, Cambridge
Finansiranje / projekti:
- Bulgarian National Science Fund (BNSF)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200042 (Univerzitet u Beogradu, Institut za molekularnu genetiku i genetičko inženjerstvo) (RS-MESTD-inst-2020-200042)
DOI: 10.1039/d1nj01659h
ISSN: 1144-0546
WoS: 000668628800001
Scopus: 2-s2.0-85111388277
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Kurutos, Atanas AU - Nikodinović-Runić, Jasmina AU - Veselinović, Aleksandar AU - Veselinović, Jovana B. AU - Kamounah, Fadhil S. AU - Ilić-Tomić, Tatjana PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1444 AB - Herein we present our work on the synthesis, investigation of the photophysical properties, interactions with nucleic acids, molecular docking, and imaging application of three carbocyanine dyes. The described low-molecular-weight compounds were found to exhibit high resistance against photobleaching and showed promising optical properties as fluorescent labeling agents for ribonucleic acids. They form strong biocomplexes (log K-s = 6.11-7.84) and revealed remarkable sensitivity towards RNA, reaching up to a 379 times increase of the emission signal when bound to AU-rich sequences. According to the score values obtained from the molecular docking studies, the compounds show strong binding affinity towards RNA macromolecules. All fluorophores exhibit significant cell tolerance since they were found to be 16 to 60 times less toxic against MRC5 cells (healthy human fibroblasts) compared to the conventional Thiazole Orange - TO. The IC50 concentrations for the compounds were calculated up to 40 mu M in human fibroblasts MRC5, A549 adenocarcinomic human alveolar basal epithelial cells, the HCT116 human colon cancer cell line, and MDA-MB-231 adenocarcinoma cells. Analyzing the dyes for preferential cytotoxicity towards cancer cell lines in comparison to the normal human fibroblasts, we found a candidate exhibiting promising anticancer potential. Based on the selectivity (Si) towards cancer cells and more specifically against difficult to treat colon HCT116 carcinoma, we can suggest these small molecules as an interesting platform for further development. We have also demonstrated the efficiency of the carbocyanines as staining agents for in vivo labeling of human cells as well as microbial and eukaryotic cells. PB - Royal Soc Chemistry, Cambridge T2 - New Journal of Chemistry T1 - RNA-targeting low-molecular-weight fluorophores for nucleoli staining: synthesis, in silico modelling and cellular imaging EP - 12829 IS - 29 SP - 12818 VL - 45 DO - 10.1039/d1nj01659h ER -
@article{ author = "Kurutos, Atanas and Nikodinović-Runić, Jasmina and Veselinović, Aleksandar and Veselinović, Jovana B. and Kamounah, Fadhil S. and Ilić-Tomić, Tatjana", year = "2021", abstract = "Herein we present our work on the synthesis, investigation of the photophysical properties, interactions with nucleic acids, molecular docking, and imaging application of three carbocyanine dyes. The described low-molecular-weight compounds were found to exhibit high resistance against photobleaching and showed promising optical properties as fluorescent labeling agents for ribonucleic acids. They form strong biocomplexes (log K-s = 6.11-7.84) and revealed remarkable sensitivity towards RNA, reaching up to a 379 times increase of the emission signal when bound to AU-rich sequences. According to the score values obtained from the molecular docking studies, the compounds show strong binding affinity towards RNA macromolecules. All fluorophores exhibit significant cell tolerance since they were found to be 16 to 60 times less toxic against MRC5 cells (healthy human fibroblasts) compared to the conventional Thiazole Orange - TO. The IC50 concentrations for the compounds were calculated up to 40 mu M in human fibroblasts MRC5, A549 adenocarcinomic human alveolar basal epithelial cells, the HCT116 human colon cancer cell line, and MDA-MB-231 adenocarcinoma cells. Analyzing the dyes for preferential cytotoxicity towards cancer cell lines in comparison to the normal human fibroblasts, we found a candidate exhibiting promising anticancer potential. Based on the selectivity (Si) towards cancer cells and more specifically against difficult to treat colon HCT116 carcinoma, we can suggest these small molecules as an interesting platform for further development. We have also demonstrated the efficiency of the carbocyanines as staining agents for in vivo labeling of human cells as well as microbial and eukaryotic cells.", publisher = "Royal Soc Chemistry, Cambridge", journal = "New Journal of Chemistry", title = "RNA-targeting low-molecular-weight fluorophores for nucleoli staining: synthesis, in silico modelling and cellular imaging", pages = "12829-12818", number = "29", volume = "45", doi = "10.1039/d1nj01659h" }
Kurutos, A., Nikodinović-Runić, J., Veselinović, A., Veselinović, J. B., Kamounah, F. S.,& Ilić-Tomić, T.. (2021). RNA-targeting low-molecular-weight fluorophores for nucleoli staining: synthesis, in silico modelling and cellular imaging. in New Journal of Chemistry Royal Soc Chemistry, Cambridge., 45(29), 12818-12829. https://doi.org/10.1039/d1nj01659h
Kurutos A, Nikodinović-Runić J, Veselinović A, Veselinović JB, Kamounah FS, Ilić-Tomić T. RNA-targeting low-molecular-weight fluorophores for nucleoli staining: synthesis, in silico modelling and cellular imaging. in New Journal of Chemistry. 2021;45(29):12818-12829. doi:10.1039/d1nj01659h .
Kurutos, Atanas, Nikodinović-Runić, Jasmina, Veselinović, Aleksandar, Veselinović, Jovana B., Kamounah, Fadhil S., Ilić-Tomić, Tatjana, "RNA-targeting low-molecular-weight fluorophores for nucleoli staining: synthesis, in silico modelling and cellular imaging" in New Journal of Chemistry, 45, no. 29 (2021):12818-12829, https://doi.org/10.1039/d1nj01659h . .