Naslov
Rhodanine derivatives as anticancer agents - QSAR and molecular docking studies

Autori
Molnar, Maja ; Lončarić, Melita ; Opačak-Bernardi, Teuta ; Glavaš-Obrovac, Ljubica ; Rastija, Vesna

Izvornik
Anti-Cancer Agents in Medicinal Chemistry (1871-5206) 23 (2022), 7; 839-846

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
QSAR ; T cell lymphoma ; c-Src ; cytotoxicity ; molecular docking ; rhodamine ; tyrosine kinase

Sažetak
Background: Rhodanine derivatives have a proven wide range of biological activities. Objective: The aim of this study was to evaluate the cytotoxic effect of a series of rhodanine derivatives and investigate the quantitative structure-activity relationships, as well as binding modes to tyrosine kinase. Methods: Cytotoxic effect on cell proliferation (CaCo-2, HeLa, MDCK-1, Hut-78, K562) in vitro was evaluated by the MTT viability assay. QSAR analysis was performed with Dragon descriptors using QSARINS software. Molecular docking was performed on the tyrosin kinase (c-Src) (PDB ID: 3G6H) using iGEMDOCK. Results: Compounds with the best inhibiting activity toward all cell lines were the ones possessing only one group in the C2 of the phenyl ring. QSAR study of the cytotoxic activity against Human T cell lymphoma achieved the model that satisfies the fitting and internal cross- validation criteria (R2 = 0.75 ; Q2LOO = 0.64). Descriptors included in the model (MATS2e, MATs7e, RDF060p) revealed the importance of the presence of atoms with higher polarizability in the outer region of molecules. The findings of the molecular docking study performed on the c-Src are in accordance with the results of the QSAR study. The key interactions with binding site residues were achieved through oxygen atoms from phenoxy and rhodanine groups and rhodanine sulphur atom. Conclusion: Rhodanine derivatives could be developed as novel tyrosine kinase inhibitors in the treatment of leukemia.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA