Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity
Nema prikaza
Autori
Svircev, MilosPopsavin, Mirjana
Pavić, Aleksandar
Vasiljević, Branka
Rodić, Marko V.
Đokić, Sanja
Kesić, Jelena
Sreco Zelenović, Bojana
Popsavin, Velimir
Kojić, Vesna
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4 ' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminar...y SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 mu M.
Ključne reči:
Zebrafish model / Thiazole bioisosteres / SAR / MTT assay / In vivo toxicity / GoniofufuroneIzvor:
Bioorganic Chemistry, 2022, 121Izdavač:
- Academic Press Inc Elsevier Science, San Diego
Finansiranje / projekti:
- Serbian Academy of Sciences and Arts under the Strategic projects programme [01-2019-F65, F-130]
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200125 (Univerzitet u Novom Sadu, Prirodno-matematički fakultet) (RS-MESTD-inst-2020-200125)
- 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: 10.1016/j.bioorg.2022.105691
ISSN: 0045-2068
PubMed: 35217378
WoS: 000780194700002
Scopus: 2-s2.0-85124994961
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Svircev, Milos AU - Popsavin, Mirjana AU - Pavić, Aleksandar AU - Vasiljević, Branka AU - Rodić, Marko V. AU - Đokić, Sanja AU - Kesić, Jelena AU - Sreco Zelenović, Bojana AU - Popsavin, Velimir AU - Kojić, Vesna PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1561 AB - The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4 ' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 mu M. PB - Academic Press Inc Elsevier Science, San Diego T2 - Bioorganic Chemistry T1 - Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity VL - 121 DO - 10.1016/j.bioorg.2022.105691 ER -
@article{ author = "Svircev, Milos and Popsavin, Mirjana and Pavić, Aleksandar and Vasiljević, Branka and Rodić, Marko V. and Đokić, Sanja and Kesić, Jelena and Sreco Zelenović, Bojana and Popsavin, Velimir and Kojić, Vesna", year = "2022", abstract = "The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4 ' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 mu M.", publisher = "Academic Press Inc Elsevier Science, San Diego", journal = "Bioorganic Chemistry", title = "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity", volume = "121", doi = "10.1016/j.bioorg.2022.105691" }
Svircev, M., Popsavin, M., Pavić, A., Vasiljević, B., Rodić, M. V., Đokić, S., Kesić, J., Sreco Zelenović, B., Popsavin, V.,& Kojić, V.. (2022). Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity. in Bioorganic Chemistry Academic Press Inc Elsevier Science, San Diego., 121. https://doi.org/10.1016/j.bioorg.2022.105691
Svircev M, Popsavin M, Pavić A, Vasiljević B, Rodić MV, Đokić S, Kesić J, Sreco Zelenović B, Popsavin V, Kojić V. Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity. in Bioorganic Chemistry. 2022;121. doi:10.1016/j.bioorg.2022.105691 .
Svircev, Milos, Popsavin, Mirjana, Pavić, Aleksandar, Vasiljević, Branka, Rodić, Marko V., Đokić, Sanja, Kesić, Jelena, Sreco Zelenović, Bojana, Popsavin, Velimir, Kojić, Vesna, "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity" in Bioorganic Chemistry, 121 (2022), https://doi.org/10.1016/j.bioorg.2022.105691 . .