Events9th International Electronic Conference on Medicinal Chemistry
Published
with-doi10.3390/ECMC2023-15593 (registering DOI)
This submission belongs to the session S4. New Small molecules as drug candidates of the event 9th International Electronic Conference on Medicinal Chemistry
Published date
01 Nov, 2023
Academic Editor
author-avatarMaria Emília Sousa
Citation
Vitali Boitsov, Anton Kornev, Alexander Stepakov, Study of cytotoxicity of spirosubstituted with acenaphthylen-1(2H)-one and aceanthrylen-1(2H)-one fragments cyclopropa[a]pyrrolizidines and 3-azabicyclo[3.1.0]hexanes against tumor cell lines, in Proceedings of 9th International Electronic Conference on Medicinal Chemistry, 1 November–30 November 2023, MDPI: Basel, Switzerland, doi: 10.3390/ECMC2023-15593
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Study of cytotoxicity of spirosubstituted with acenaphthylen-1(2H)-one and aceanthrylen-1(2H)-one fragments cyclopropa[a]pyrrolizidines and 3-azabicyclo[3.1.0]hexanes against tumor cell lines

Anton Kornev 1
1. Saint Petersburg National Research Academic University of the Russian Academy of Sciences, St Petersburg, Russia, Russia
2. Saint Petersburg State University, St Petersburg, Rusia, Russia
3. Saint Petersburg National Research Academic University of the Russian Academy of Sciences, Saint Petersburg, Russia, Russia
Abstract

Oncological diseases are one of the most common public health problems and second leading cause of death after cardiovascular disease. Natural products or synthetic compounds inspired from natural products continue to be excellent sources for new drug candidates. Pyrrolizidines and 3-azabicyclo[3.1.0]hexanes are important classes of heterocyclic compounds with diverse pharmacological activities including anticancer activity. Here we report study of cytotoxicity of newly developed spirosubstituted with acenaphthylen-1(2H)-one and aceanthrylen-1(2H)-one fragments cyclopropa[a]pyrrolizidines and 3-azabicyclo[3.1.0]hexanes against tumor cell lines. The results of antiproliferative activity study showed that spiroadducts with either acenaphthylen-1(2H)-one or aceanthrylen-1(2H)-one framework have shown significant activity with IC50 up to 1 μg/mL. Confocal microscopy study showed diffuse distribution of granular actin in the cell cytoplasm with disappearance of actin filaments. Number of cells with filopodium-like membrane protrusions was also reduced after treatment with some of tested compounds. The obtained results support the antitumor effect of the studied compounds.

Keywords
cyclopropa[a]pyrrolizidine
3-azabicyclo[3.1.0]hexane
acenaphthylen-1(2H)-one
ace-anthrylen-1(2H)-one
in vitro antitumor activity
human cervical carcinoma (HeLa) cell line
human erythroleukemia (K-562) cell line
human melanoma (Sk-mel-2) cell line
Manuscript
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