Synthesis of Novel Artemisinin Derivatives With Potent Anticancer Activities Against Multidrug-resistant Cancer Cells
2023
Autori:
Opsenica, IgorKoračak, Ljiljana
Lupšić, Ema
Jovanović, Mirna
Novaković, Miroslav
Pešić, Milica
Tip dokumenta:
Konferencijski prilog (Objavljena verzija)
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© 2023 by the Royal Society of Chemistry
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Derivatization of artemisinin, a natural sesquiterpene lactone, and its synthetic analog artesunate, is of significant interest in medicinal chemistry due to their versatile biological activity, including antimalarial and anticancer. The importance of the pyrimidine scaffold in medicinal chemistry is evidenced by its presence in many natural products and approved drugs, as well as in numerous biologically active compounds.
In this study, we report the synthesis of several novel hybrid molecules comprising two pharmacophores
(artesunic acid and pyrimidine scaffold) and their activity against sensitive and multidrug‐resistant (MDR)
human non‐small cell lung carcinoma (NSCLC) cells. The synthesis of novel artemisinin-pyrimidine hybrid
molecules was accomplished via amide bond formation between artesunic acid and pyrimidine derivatives. A lead compound was identified through structure activity relationship (SAR) studies. Several hybrids were capable of evading the MDR phenotype, increasing the sensitivity of MDR NSCLC cells toward doxorubicin and displayed inhibitory activity against P-glycoprotein.
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200168 (Univerzitet u Beogradu, Hemijski fakultet) (RS-MESTD-inst-2020-200168)
U:
- Book of abstracts: 22nd European Symposium on Organic Chemistry Ghent: ESOC 2023; 2023 Jul 9-13; Ghent, Belgium. Cambridge: Royal Society of Chemistry; 2023. p. 213.