Synthesis of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives as potential anti-diabetic and anticancer agents

Abstract

In this work, we developed a series of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives 4(a-e) via a one-pot multicomponent reaction. The structures of the compounds were confirmed using analytical and spectroscopic techniques. Also, the synthesized compounds were screened for their anti-diabetic activity, cytotoxicity and in silico studies. The activity results suggested that the compound 4e exhibited least IC₅₀ values of 0.055 ± 0.002 µM, 0.050 ± 0.002 µM and 0.009 ± 0.001 µM for α-amylase, α-glucosidase and cytotoxicity respectively. Further, in silico molecular docking results revealed that all the obtained compounds effectively interacted with exo-β-D-glucosaminidase and P38 MAP kinase proteins with good binding energies. In that, 4e compound established the least binding energy of −9.6 and −9.1 kcal/mol, respectively. Moreover, our synthesized compounds were subjected to ADME studies, which suggested that all the synthesized compounds obeyed all five rules with good bioavailability and were suitable as drug leads against anti-diabetic and anticancer treatment.

Keywords:

• Pyrimidine derivatives
• α-amylase and α-glucosidase
• cytotoxicity
• SAR
• in silico docking and ADME

Acknowledgments

The authors are thankful to the Chairman, Department of Chemistry, Kuvempu University, Shankaraghatta, for providing the laboratory facilities. The authors are also thankful to SAIF, Mysore University and Karnataka University, Dharawad, for providing the spectral data.

Authors’ contributions

Sukanya S H: Methodology, Investigation, Writing – original draft. Talavara Venkatesh: Methodology, Investigation, Supervision, Writing and editing. Shanavaz H: Molecular interaction and ADME studies.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supporting information

This includes spectra’s of the synthesized compounds (IR, ¹H NMR, ¹³C NMR, and HRMS).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.