Structure-Activity Relationship Prediction-Based Synthesis and Cytotoxicity Evaluation against the HEp-2 Laryngeal Carcinoma Cell of Isoflavone-Cytisine Mannich Bases.

Autor: Mrug G; V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv, 02094, Ukraine., Hodyna D; V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv, 02094, Ukraine., Metelytsia L; V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv, 02094, Ukraine., Kovalishyn V; V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv, 02094, Ukraine., Trokhimenko O; Shupyk National Healthcare University of Ukraine, Kyiv, 04112, Ukraine., Bondarenko S; Department of Food Chemistry, National University of Food Technologies, Kyiv, 01601, Ukraine., Kondratyuk K; V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv, 02094, Ukraine., Kozitskiy A; Enamine Ltd., Kyiv, 02094, Ukraine., Frasinyuk M; V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv, 02094, Ukraine.; Enamine Ltd., Kyiv, 02094, Ukraine.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2023 Aug; Vol. 20 (8), pp. e202300560. Date of Electronic Publication: 2023 Aug 04.
DOI: 10.1002/cbdv.202300560
Abstrakt: QSAR analysis of previously synthesized and nature-inspired virtual isoflavone-cytisine hybrids against the HEp-2 laryngeal carcinoma cell lines was performed using the OCHEM web platform. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds such as 8-cytisinylmethyl derivatives of 5,7- and 6,7-dihydroxyisoflavones. The synthetic procedure for selective aminomethylation of 5,7-dihydroxyisoflavones with cytisine was developed. In vitro testing identified compound 7 f with cisplatin-level cytotoxicity against HEp-2 cell lines and compound 10 which was twice active than cisplatin after 72 h of incubation.
(© 2023 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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