Design, synthesis, molecular docking study and molecular dynamics simulation of new coumarin-pyrimidine hybrid compounds having anticancer and antidiabetic activity.
| Title: | Design, synthesis, molecular docking study and molecular dynamics simulation of new coumarin-pyrimidine hybrid compounds having anticancer and antidiabetic activity. |
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| Authors: | Toan DN; Faculty of Chemistry, Thai Nguyen University of Education, 20 Luong Ngoc Quyen, Thai Nguyen, Viet Nam.; Faculty of Chemistry, VNU University of Science, 19 Le Thanh Tong, Hoan Kiem, Ha Noi, Viet Nam.; Thanh ND; Faculty of Chemistry, VNU University of Science, 19 Le Thanh Tong, Hoan Kiem, Ha Noi, Viet Nam.; Truong MX; Faculty of Chemistry, Thai Nguyen University of Education, 20 Luong Ngoc Quyen, Thai Nguyen, Viet Nam.; Van DT; Faculty of Chemistry, Thai Nguyen University of Education, 20 Luong Ngoc Quyen, Thai Nguyen, Viet Nam.; Thanh NN; Faculty of Chemical Technology, Ha Noi University of Industry, 298 Cau Dien Road, North Tu Liem, Ha Noi, Viet Nam. |
| Source: | Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents [Med Chem Res] 2023; Vol. 32 (6), pp. 1143-1162. Date of Electronic Publication: 2023 Apr 21. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer Country of Publication: United States NLM ID: 9211347 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1054-2523 (Print) Linking ISSN: 10542523 NLM ISO Abbreviation: Med Chem Res Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Publication: New York : Springer; Original Publication: Cambridge, MA : Birkhäuser Boston, c1991- |
| Abstract: | Coumarin-pyrimidine hybrid compounds were synthesized by condensation reaction of α,β-unsaturated ketones of 6-acetyl-5-hydroxy-4-methylcoumarin with guanidine. The reaction yields were of 42-62%. The antidiabetic and anticancer activities of these compounds were examined. These compounds displayed low toxicity to two cancer cell lines (including KB and HepG2 ones), but exhibited remarkably active against α-amylase with IC50 values of 102.32 ± 1.15 μM to 249.52 ± 1.14 μM and against α-glucosidase with IC50 values of 52.16 ± 1.12 μM to 184.52 ± 1.15 μM. Amongst these compounds, 6c was the best inhibitory activity against α-amylase, and 6f had the highest activity against α-glucosidase. The kinetics of inhibitor 6f was competitive α-glucosidase inhibitor property. ADMET predictions showed that almost all synthesized compounds exhibited drug-like activity. IFD and MD simulations were carried out on enzymes 4W93 and 5NN8 to elucidate inhibitory potential of 6c and 6f against tested enzymes. The binding free energy calculation by MM-GBSA approach showed that Coulomb, lipophilic and van der Waals energy terms are major contributors for the inhibitor binding. Molecular dynamics simulations in water solvent system were carried out for the 6f/5NN8 complex to elucidate the variability of active interactions between ligand 6f and active pockets of this enzyme.; (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.) |
| Competing Interests: | Conflict of interestThe authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Coumarin; Hybrid compounds; Induced fit docking; Pyrimidine; Type 2 diabetes |
| Entry Date(s): | Date Created: 20230612 Latest Revision: 20230928 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10119543 |
| DOI: | 10.1007/s00044-023-03060-8 |
| PMID: | 37305206 |
| Database: | MEDLINE |
Journal Article