Unsymmetrical Trifluoromethyl Methoxyphenyl β-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity | Sciact - CRIS-system of Boreskov Institute of Catalysis

Unsymmetrical Trifluoromethyl Methoxyphenyl β-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity Full article

Journal

Molecules
ISSN: 1420-3049

Output data

Year: 2021, Volume: 26, Number: 21, Article number : 6466, Pages count : 21 DOI: 10.3390/molecules26216466

Tags

copper(II); diketonates; cytotoxic activity; antimicrobial activity; anticancer agents

Authors

Khamidullina Liliya A. ^1,2 , Puzyrev Igor S. ¹ , Burygin Gennady L. ³ , Dorovatovskii Pavel V. ⁴ , Zubavichus Yan V. ⁵ , Mitrofanova Anna V. ⁶ , Khrustalev Victor N. ^6,7 , Timofeeva Tatiana V. ⁸ , Slepukhin Pavel A. ¹ , Tobysheva Polina D. ² , Pestov Alexander V. ^1,2 , Solari Euro ⁹ , Tskhovrebov Alexander G. ⁶ , Nenajdenko Valentine G. ¹⁰

Affiliations

1	Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22 Sofia Kovalevskaya street, 620137 Ekaterinburg, Russia
2	Institute of Natural Sciences and Mathematics, Ural Federal University, 19 Mira Street, 620002 Ekaterinburg, Russia
3	Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, 410049 Saratov, Russia
4	NRC “Kurchatov Institute”, 1 Acad. Kurchatov Sq., 123182 Moscow, Russia
5	Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave.5, 630090 Novosibirsk, Russia
6	Department of Inorganic Chemistry, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklay street, 117198 Moscow, Russia
7	Zelinsky Institute of Organic Chemistry RAS, Leninsky Prosp. 47, 119991 Moscow, Russia
8	Department of Chemistry, New Mexico Highlands University, Las Vegas, NM 87701, USA
9	Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH 1015 Lausanne, Switzerland
10	Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1/3, 119991 Moscow, Russia

Funding (5)

1	Russian Foundation for Basic Research	20-53-00006 (АААА-А20-120111090048-1)
2	Ministry of Science and Higher Education of the Russian Federation	075-00578-19-00 (АААА-А19-119011790132-7)
3	Ministry of Science and Higher Education of the Russian Federation	АААА-А19-119012490006-1
4	Ministry of Science and Higher Education of the Russian Federation	075-03-2020-223 (FSSF-2020-0017)
5	National Science Foundation	DMR-1523611

Copper(II) complexes with 1,1,1-trifluoro-4-(4-methoxyphenyl)butan-2,4-dione (HL1) were synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single crystal X-ray diffraction. The biological properties of HL1 and cis-[Cu(L1)2(DMSO)] (3) were examined against Gram-positive and Gram-negative bacteria and opportunistic unicellular fungi. The cytotoxicity was estimated towards the HeLa and Vero cell lines. Complex 3 demonstrated antibacterial activity towards S. aureus comparable to that of streptomycin, lower antifungal activity than the ligand HL1 and moderate cytotoxicity. The bioactivity was compared with the activity of compounds of similar structures. The effect of changing the position of the methoxy group at the aromatic ring in the ligand moiety of the complexes on their antimicrobial and cytotoxic activity was explored. We propose that complex 3 has lower bioavailability and reduced bioactivity than expected due to strong intermolecular contacts. In addition, molecular docking studies provided theoretical information on the interactions of tested compounds with ribonucleotide reductase subunit R2, as well as the chaperones Hsp70 and Hsp90, which are important biomolecular targets for antitumor and antimicrobial drug search and design. The obtained results revealed that the complexes displayed enhanced affinity over organic ligands. Taken together, the copper(II) complexes with the trifluoromethyl methoxyphenyl-substituted β-diketones could be considered as promising anticancer agents with antibacterial properties.

Khamidullina L.A. , Puzyrev I.S. , Burygin G.L. , Dorovatovskii P.V. , Zubavichus Y.V. , Mitrofanova A.V. , Khrustalev V.N. , Timofeeva T.V. , Slepukhin P.A. , Tobysheva P.D. , Pestov A.V. , Solari E. , Tskhovrebov A.G. , Nenajdenko V.G.
Unsymmetrical Trifluoromethyl Methoxyphenyl β-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity
Molecules. 2021. V.26. N21. 6466 :1-21. DOI: 10.3390/molecules26216466 WOS Scopus РИНЦ AN PMID OpenAlex

Submitted:	Sep 3, 2021
Accepted:	Oct 21, 2021
Published online:	Oct 26, 2021
Published print:	Nov 1, 2021

Web of science:	WOS:000726978400001
Scopus:	2-s2.0-85118401056
Elibrary:	47522602
Chemical Abstracts:	2021:2518612
PMID:	34770875
OpenAlex:	W3210164212

DB	Citing
Scopus	9
Web of science	8
Elibrary	9
OpenAlex	9