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Design and Synthesis of Aspirin-chalcone Mimic Conjugates as Potential Anticancer Agents.
- Source :
-
Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2024; Vol. 24 (7), pp. 544-557. - Publication Year :
- 2024
-
Abstract
- Background: Extensive research has been conducted on aspirin, a widely recognized NSAID medication, regarding its potential as an anticancer agent. Studies have revealed its ability to trigger cell death in different types of cancer cells.<br />Methods: A set of aspirin-chalcone mimic conjugates 5a-k and 6a-d utilizing the freshly prepared acid chloride of aspirin moiety has been designed and synthesized. To evaluate the newly developed compounds, the NCI 60- cell line panel was employed to assess their anti-proliferative properties. Subsequently, cell cycle analysis was conducted along with an examination of the compounds' impact on the levels of p53, Bax, Bcl-2, active caspase- 3, and their inhibition mechanism of tubulin polymerization.<br />Results: Derivative 6c displayed the best anticancer activity among the tested series while 6d was the best against breast cancer MDA-MB-468, therefore both of them were selected for the 5-dose stage, however, targeting MDA-MB-468, PI-flow cytometry of compound 6d proved the triggered cell growth arrest at the G1/S phase avoiding the mitotic cycle in MDA-MB-468 cells. Similarly, the upregulation of oncogenic parameters such as caspase-3, p53, and Bax/Bcl-2, along with the inhibition of PARP-1 enzyme level, was observed with compound 6d. This compound also exhibited a significant ability to induce apoptosis and disrupt the intracellular microtubule network through a promising activity as a tubulin polymerization inhibitor with IC <subscript>50</subscript> = 1.065 ± 0.024 ng/ml. Furthermore, to examine the manner in which compound 6d binds to the active pocket of the tubulin polymerization enzyme, a molecular docking study was conducted.<br />Conclusion: The study indicated that compound 6d could be a powerful microtubule-destabilizing agent. Therefore, further research on 6d could be worthwhile.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Subjects :
- Humans
Structure-Activity Relationship
Molecular Structure
Dose-Response Relationship, Drug
Molecular Docking Simulation
Apoptosis drug effects
Chalcone pharmacology
Chalcone chemistry
Chalcone chemical synthesis
Cell Line, Tumor
Chalcones pharmacology
Chalcones chemistry
Chalcones chemical synthesis
Cell Cycle drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Drug Design
Aspirin pharmacology
Aspirin chemistry
Cell Proliferation drug effects
Drug Screening Assays, Antitumor
Subjects
Details
- Language :
- English
- ISSN :
- 1875-5992
- Volume :
- 24
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Anti-cancer agents in medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38204260
- Full Text :
- https://doi.org/10.2174/0118715206280025231213065519