Synthesis of Novel Coumarin-Appended Dihydrothiopyrimidinones and Evaluation of Their Binding Interactions with Bovine Serum Albumin

Abstract

A novel one-pot, single-step multicomponent approach for the acid-catalyzed synthesis of coumarin-appended dihydrothiopyrimidinones is developed by utilizing a coumarin-based 1,3-biselectrophile, thiourea, and different aldehydes at reflux temperature. This method utilizes cheap solvents (ethanol/acetonitrile) and enables the construction of a library of highly substituted coumarin-based dihydrothiopyrimidinones (CDHTPs), demonstrating a wide range of substrate compatibility and affording very good yields of products. The coumarin ring is incorporated in the dihydrothiopyrimidinones due to its wide range of biological efficacy and its excellent fluorescence properties in the visible region of the spectrum. The binding interactions of the obtained CDHTPs to bovine serum albumin (BSA) protein are evaluated using spectroscopic techniques, with ethyl 6-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-4-(4-hydroxyphenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate exhibiting the strongest binding interaction (K _d = 2.3 μM. Various site markers are used in displacement assays, revealing that the above compound is bound to the subdomain IB. The structures of the obtained CDHTPs are confirmed by NMR and mass spectrometry.

Key words

multicomponent reaction - Biginelli synthesis - BSA binding - coumarins - dihydrothiopyrimidinones

Publication History

Received: 12 March 2025

Accepted after revision: 10 April 2025

Article published online:
05 June 2025

• References and Notes

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