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Quinoline–1,3,4-Oxadiazole Conjugates: Synthesis, Anticancer Evaluation, and Molecular Modelling Studies.
- Source :
- Polycyclic Aromatic Compounds; 2023, Vol. 43 Issue 7, p6437-6457, 21p
- Publication Year :
- 2023
-
Abstract
- Cancer continues to have overwhelming impacts on human health and the development of new chemotherapeutics. Molecular hybridization has thus been valued as a structure-based drug design approach to drugs with enhanced efficacy. Herein, we report the multistep synthesis of quinoline–2-mercapto-1,3,4-oxadiazole conjugates and their cytotoxicity evaluation. Compound 4j 2-[(5-bromopentyl)thio]-5-[(quinolin-8-yloxy)methyl]-1,3,4-oxadiazole showed the best cytotoxicity to pancreatic (MIA PaCa-2) and colorectal (HCT116) cancer cells with IC<subscript>50</subscript> values of 29.19 ± 0.99 and 75.10 ± 1.87 µM, respectively. The compound is also less cytotoxic to non-cancerous human primary dermal fibroblast cells with IC<subscript>50</subscript> = 91.87 ± 1.29 µM compared to the parent compound 8-hydroxyquinoline (IC<subscript>50</subscript> = 72.36 ± 4.23 µM). ADME properties prediction suggested the drug-likeness of potent compounds while molecular docking and molecular dynamics simulations with doublecortin-like kinase (DCLK1) revealed the compounds' stable binding interactions at the kinase domain. Overall, the results illuminate compound 4j as a structural model to furnish new cytotoxic agents against pancreatic and colorectal cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10406638
- Volume :
- 43
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Polycyclic Aromatic Compounds
- Publication Type :
- Academic Journal
- Accession number :
- 169784410
- Full Text :
- https://doi.org/10.1080/10406638.2022.2117205