Synthesis, Characterization, and Biological Evaluation of Meldrum’s Acid Derivatives: Dual Activity and Molecular Docking Study(Article)(Open Access)
- aDepartment of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Al Jouf, Sakaka, 72388, Saudi Arabia
- bDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Al Jouf, Sakaka, 72388, Saudi Arabia
- cCenter for Ultrasound Molecular Imaging and Therapeutics, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15260, United States
- dCentre for Organic Chemistry, School of Chemistry, University of the Punjab, Lahore, 54590, Pakistan
- eChemistry Department, College of Science, Jouf University, Al Jouf, Sakaka, 72388, Saudi Arabia
- fDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Sakaka, 72388, Saudi Arabia
- gDepartment of Clinical Pharmacy, College of Pharmacy, Jouf University, Al Jouf, Sakaka, 72388, Saudi Arabia
- hUniversity of Kragujevac, Faculty of Science, Radoja Domanovića 12, Kragujevac, 34000, Serbia
- iUniversity of Kragujevac, Department of Science, Institute for Information Technologies Kragujevac, Jovana Cvijića bb, Kragujevac, 34000, Serbia
Abstract
In the presented study, eight novel Meldrum’s acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum’s acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 μM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 μM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster. © 2023 by the authors.
Indexed keywords
| EMTREE drug terms: | benzylidene derivativebenzylidene meldrum acidDNA topoisomerase (ATP hydrolysing)DNA topoisomerase (ATP hydrolysing) Bnucleophileunclassified drugvanillin |
|---|---|
| EMTREE medical terms: | A-549 cell lineantimicrobial activityantineoplastic activityArticlebinding affinitybiological activitycarbon nuclear magnetic resonanceclinical articlecytotoxicitydrug screeningdrug synthesisEscherichia coliHeLa cell linehumanhuman cellLS174T cell lineminimum inhibitory concentrationmolecular dockingMTT assayproton nuclear magnetic resonancestructure activity relationsubstitution reaction |
Chemicals and CAS Registry Numbers:
DNA topoisomerase (ATP hydrolysing); vanillin, 121-33-5
Funding details
| Funding sponsor | Funding number | Acronym |
|---|---|---|
| Deanship of Scientific Research, University of Jordan | DSR2022-RG-0148 | DSR |
| Deanship of Scientific Research, University of Jordan | DSR |
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1
This work was funded by the Deanship of Scientific Research at Jouf University under Grant Number (DSR2022-RG-0148).
- ISSN: 14248247
- Source Type: Journal
- Original language: English
- DOI: 10.3390/ph16020281
- Document Type: Article
- Publisher: MDPI
Bukhari, S.N.A.; Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Al Jouf, Sakaka, Saudi Arabia;
Janković, N.; University of Kragujevac, Department of Science, Institute for Information Technologies Kragujevac, Jovana Cvijića bb, Kragujevac, Serbia;
© Copyright 2023 Elsevier B.V., All rights reserved.
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