ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Exploring the antimicrobial, genotoxic, and anticancer potential of novel dihydropyrimidinones synthesized via Biginelli reaction: an integrated in vitro and in silico study

L. Benazir Ali, A. Subramani, H. Thajudeen, T. K. Shabeer, and P. Saravanan

PG and Research Department of Chemistry, The New College, Chennai, India

E-mail: subuchem71@gmail.com

Received: 1 June 2024  Accepted: 6 August 2025

Abstract:

Dihydropyrimidin-2(1H)-ones (DHPMs) have garnered significant attention in synthetic and medicinal organic chemistry because of their remarkable biological and therapeutic potential. In this study, DHPM derivatives were synthesized using the Biginelli reaction starting from bisdialdehyde to identify potential lead compounds. The predicted lipophilicity values of the synthesized DHPMs were in the range 2.77- 4.3. Log Po/w indicates the drug-likeness properties of the synthesized compounds. Structural confirmation was achieved through advanced spectroscopic techniques. DHPMs 7 and 9 demonstrated strong antimicrobial activity, effectively targeting a wide range of microbes. Molecular modeling further revealed that DHPM 9 exhibited a notable docking score of -8.161 kcal/mol, indicating a high binding affinity for VEGFR-2 kinase. According to HOMO and LUMO studies, DHPM 1 is the most stable of the DHPMs (ΔE = 4.838 eV), while DHPM 9 is the most reactive with the smallest energy gap (ΔE = 3.677 eV). The anticancer potentials of synthesized were evaluated using A549 lung cancer cell. The work highlights significant cytotoxic effects on A549 cells with IC50 values of 1.56 μg/mL. The genotoxicity assay is performed using agarose gel electrophoresis, which is an appropriate method for assessing mutagenic potential. The results indicate that compound 7 exhibits moderate genotoxic potential at 125 μg /ml. DHPM 9 exhibits strong activity against Enterococcus faecalis, with an MIC range of 6.30 μg/mL, and is chemically more reactive than the other compounds, which is consistent with the strongest anticancer and antimicrobial activity values. DHPMs 7 and 9 stood out with the highest cumulative release percentages at the final time point (68.54–74.85%), showcasing their efficient delivery capabilities. The research aims to contribute to public health by evaluating the biological effects and therapeutic potentials of the synthesized compounds.

Graphical abstract

Keywords: Bisdialdehyde; Molecular modeling; Genotoxicity; Biginelli reaction; DFT; Molecular simulation

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04297-w

Chemical Papers 79 (11) 7939–7965 (2025)