Discovery of indoleninyl-pyrazolo[3,4-b]pyridines as potent chemotherapeutic agents against colorectal cancer cells
Document Type
Article
Publication Date
5-1-2024
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.
Keywords
Indolenines, Pyrazolo3, b ]pyridines, X-ray crystallography, DNA binding, Cytotoxicity
Divisions
InstituteofBiologicalSciences,CHEMISTRY
Funders
Universiti Sains Malaysia (304/PKIMIA/6315738)
Publication Title
BIOORGANIC CHEMISTRY
Volume
146
Publisher
Elsevier
Publisher Location
525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA