Basir, Nur Husnaini and Ramle, Abdul Qaiyum and Ng, Min Phin and Tan, Chun Hoe and Tiekink, Edward R.T. and Sim, Kae Shin and Basirun, Wan Jefrey and Khairuddean, Melati (2024) Discovery of indoleninyl-pyrazolo[3,4-b]pyridines as potent chemotherapeutic agents against colorectal cancer cells. BIOORGANIC CHEMISTRY, 146. p. 107256. ISSN 0045-2068, DOI https://doi.org/10.1016/j.bioorg.2024.107256.
Full text not available from this repository.Abstract
A new series of indolenines decorated with pyrazolo3,4-b]pyridines were designed and synthesized in up to 96% yield from the acid-catalyzed cyclocondensation of 1,3-dialdehydes with 3-aminopyrazoles. X-ray crystallography on a representative derivative, 5n, revealed two close to planar conformations whereby the N-atom of the pyridyl residue was syn or anti to the pyrrole-N atom in the two independent molecules of the asymmetric unit. The computational and DNA binding data suggest that 5n is a strong DNA intercalator with the results in agreement with its potent cytotoxicity against two colorectal cancer cell lines (HCT 116 and HT-29). In contrast to doxorubicin, compounds 5k-o have higher druggability (compliance to more criteria stated in Lipinski's rule of five and Veber's rule), higher bioavailability, and better medicinal chemistry properties, indicative of their potential application as chemotherapeutical agents.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Sains Malaysia (304/PKIMIA/6315738) |
| Uncontrolled Keywords: | Indolenines; Pyrazolo3; b ]pyridines; X-ray crystallography; DNA binding; Cytotoxicity |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history |
| Divisions: | Faculty of Science > Institute of Biological Sciences Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 22 Oct 2024 05:27 |
| Last Modified: | 22 Oct 2024 05:27 |
| URI: | http://eprints.um.edu.my/id/eprint/45465 |
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