Elucidating the Mechanism of Coumarin Homodimerization Using 3-Acetylcoumarin Derivatives

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2025 Feb 13

PMID 39942755

Authors

Kristina B Simeonova

Ana I Koleva

Nevena I Petkova-Yankova

Anna-Mariya R Zlatanova

Vesela Lozanova

Rositca D Nikolova

Petko St Petkov

Affiliations

Soon will be listed here.

Abstract

The current study is a continuation of our previous investigations into the radical homodimeric reaction mechanism of 3-acetylcoumarin. In the current study, the effects of different substituents on the coumarin ring of 3-acetylcoumarin are investigated both experimentally and theoretically. Several 3-acetylcoumarin derivatives (substituted at C-6, C-7, and C-8) were tested in the optimized reaction conditions under ultrasound irradiation, and biscoumarin species were isolated and characterized. The elucidation of the substituent's effect was further investigated by means of DFT calculations (free-energy calculations, NBO analysis), both in the initial substituted coumarins and in the formed radicals. It was observed that the presence of substituents at the C-6 and C-8 positions in the coumarin moiety would not affect significantly the formation of a radical, while a group at position C-7 could either stabilize or destabilize the formed radical depending on the electronic properties of the substituent.

References

Todorov L, Saso L, Kostova I . Antioxidant Activity of Coumarins and Their Metal Complexes. Pharmaceuticals (Basel). 2023; 16(5). PMC: 10220850. DOI: 10.3390/ph16050651. View

Todorov L, Kostova I . Coumarin-transition metal complexes with biological activity: current trends and perspectives. Front Chem. 2024; 12:1342772. PMC: 10895002. DOI: 10.3389/fchem.2024.1342772. View

Koleva A, Petkova-Yankova N, Nikolova R . Ultrasound-Assisted Metal-Mediated Method for the Formation of Tetrahydro-3,3'-Disubstituted Biscoumarins. Molecules. 2018; 23(11). PMC: 6278503. DOI: 10.3390/molecules23112810. View

Lee , Yang , PARR . Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988; 37(2):785-789. DOI: 10.1103/physrevb.37.785. View

Fernandez-Pena L, Matos M, Lopez E . Recent Advances in Biologically Active Coumarins from Marine Sources: Synthesis and Evaluation. Mar Drugs. 2023; 21(1). PMC: 9864071. DOI: 10.3390/md21010037. View

Simeonova K, Koleva A, Zlatanova A, Petkova-Yankova N, Aleksandrov H, Petkov P . Experimental and Theoretical Study on the Homodimerization Mechanism of 3-Acetylcoumarin. Molecules. 2022; 27(21). PMC: 9655359. DOI: 10.3390/molecules27217228. View

Wang Y, Li Y, Cao J, Yang X, Huang J, Huang M . Research Progress of Fluorescent Probes for Detection of Glutathione (GSH): Fluorophore, Photophysical Properties, Biological Applications. Molecules. 2024; 29(18). PMC: 11434280. DOI: 10.3390/molecules29184333. View

Di Stasi L . Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs. Pharmaceuticals (Basel). 2023; 16(4). PMC: 10142712. DOI: 10.3390/ph16040511. View

Feng D, Zhang A, Yang Y, Yang P . Coumarin-containing hybrids and their antibacterial activities. Arch Pharm (Weinheim). 2020; 353(6):e1900380. DOI: 10.1002/ardp.201900380. View

10.

Singh A, Singh K, Kaur K, Singh A, Sharma A, Kaur K . Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure-Activity Relationships. Biomedicines. 2024; 12(6). PMC: 11200728. DOI: 10.3390/biomedicines12061192. View

11.

Kapidou E, Litinas K . An Overview of the Synthesis of 3,4-Fused Pyrrolocoumarins of Biological Interest. Molecules. 2024; 29(12). PMC: 11206682. DOI: 10.3390/molecules29122748. View

12.

MYERS R, Parker M, Grizzle W . The effects of coumarin and suramin on the growth of malignant renal and prostatic cell lines. J Cancer Res Clin Oncol. 1994; 120 Suppl:S11-3. DOI: 10.1007/BF01377115. View

13.

Skarga V, Matrosov A, Nichugovskiy A, Negrebetsky V, Maslov M, Boldyrev I . pH-Dependent Photoinduced Interconversion of Furocoumaric and Furocoumarinic Acids. Molecules. 2021; 26(9). PMC: 8126128. DOI: 10.3390/molecules26092800. View

14.

Balcioglu S, Karatas M, Ates B, Alici B, Ozdemir I . Therapeutic potential of coumarin bearing metal complexes: Where are we headed?. Bioorg Med Chem Lett. 2019; 30(2):126805. DOI: 10.1016/j.bmcl.2019.126805. View

15.

Liu J, Wu F, Chen L, Zhao L, Zhao Z, Wang M . Biological evaluation of coumarin derivatives as mushroom tyrosinase inhibitors. Food Chem. 2012; 135(4):2872-8. DOI: 10.1016/j.foodchem.2012.07.055. View

16.

Lyapchev R, Koleva A, Koleva I, Subev K, Madzharova I, Simeonova K . Efficient Synthesis of Fluorescent Coumarins and Phosphorous-Containing Coumarin-Type Heterocycles via Palladium Catalyzed Cross-Coupling Reactions. Molecules. 2022; 27(21). PMC: 9654183. DOI: 10.3390/molecules27217649. View

17.

Suleiman M, Almalki F, Hadda T, Kawsar S, Chander S, Murugesan S . Recent Progress in Synthesis, POM Analyses and SAR of Coumarin-Hybrids as Potential Anti-HIV Agents-A Mini Review. Pharmaceuticals (Basel). 2023; 16(11). PMC: 10675815. DOI: 10.3390/ph16111538. View

18.

Secci D, Carradori S, Bolasco A, Chimenti P, Yanez M, Ortuso F . Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives. Eur J Med Chem. 2011; 46(10):4846-52. DOI: 10.1016/j.ejmech.2011.07.017. View

19.

El-Sawy E, Abdel-Aziz M, Abdelmegeed H, Kirsch G . Coumarins: Quorum Sensing and Biofilm Formation Inhibition. Molecules. 2024; 29(19). PMC: 11478192. DOI: 10.3390/molecules29194534. View

20.

Kornicka A, Balewski L, Lahutta M, Kokoszka J . Umbelliferone and Its Synthetic Derivatives as Suitable Molecules for the Development of Agents with Biological Activities: A Review of Their Pharmacological and Therapeutic Potential. Pharmaceuticals (Basel). 2023; 16(12). PMC: 10747342. DOI: 10.3390/ph16121732. View