One-pot synthesis of cyclic-aminotropiminium carboxylate derivatives with DNA binding and anticancer properties.

Autor: Palai BB; School of Chemical Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, PO: Jatni 752050, Bhubaneswar, Odisha, India.; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400094, India., Patel SA; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400094, India.; School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, PO: Jatni 752050, Bhubaneswar, Odisha, India., Sharma NK; School of Chemical Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, PO: Jatni 752050, Bhubaneswar, Odisha, India. nagendra@niser.ac.in.; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400094, India. nagendra@niser.ac.in., Dixit M; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400094, India. manjusha@niser.ac.in.; School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, PO: Jatni 752050, Bhubaneswar, Odisha, India. manjusha@niser.ac.in.
Jazyk: angličtina
Zdroj: Communications chemistry [Commun Chem] 2022 Dec 27; Vol. 5 (1), pp. 179. Date of Electronic Publication: 2022 Dec 27.
DOI: 10.1038/s42004-022-00798-x
Abstrakt: Tropolone, a nonbenzenoid aromatic molecule, is a constituent of troponoid natural products possessing a wide range of bioactivities, including anticancer. This report describes the one-pot synthesis and mechanistic studies of fifteen fluorescent C aryl -N alkyl -substituted cyclic-aminotroponiminium carboxylate (cATC) derivatives by unusual cycloaddition and rearrangement reactions. Herein, the biochemical studies of four cATC derivatives reveal a non-intercalative binding affinity with DNA duplex. In vitro/in vivo studies show strong anti-tumor activity in three cATC derivatives. These derivatives enter the cells and localize to the nucleus and cytoplasm, which are easily traceable due to their inherent fluorescence properties. These three cATC derivatives reduce the proliferation and migration of HeLa cells more than the non-cancer cell line. They induce p38-p53-mediated apoptosis and inhibit EMT. In xenograft-based mouse models, these cATC derivatives reduce tumor size. Overall, this study reports the synthesis of DNA binding fluorescent C aryl -N alkyl -cyclic-aminotroponiminium derivatives which show anti-tumor activity with the minimum side effect.
(© 2022. The Author(s).)
Databáze: MEDLINE
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