Synthesis, anticancer evaluation, molecular docking and ADME study of novel pyrido[4',3':3,4]pyrazolo[1,5-a]pyrimidines as potential tropomyosin receptor kinase A (TrKA) inhibitors.

ABSTRACT: The starting compound 3-amino-1,7-dihydro-4H-pyrazolo[4,3-c]pyridine-4,6(5H)-dione (1) is reacted with each of diketone and β-ketoester, forming pyridopyrazolo[1,5-a]pyrimidines 4a,b and 14a,b, respectively. The compounds 4 and 14 reacted with each of aromatic aldehyde and arenediazonium salt to give the respective arylidenes and arylhydrazo derivatives, respectively. The structure of the new products was established using spectroscopic techniques. The cytotoxic activity of selected targets was tested in vitro against three cancer cell lines MCF7, HepG2 and HCT116. The data obtained from enzymatic assays of TrKA indicated that compounds 7b and 16c have the strongest inhibitory effects on TrKA with IC₅₀ = 0.064 ± 0.0037 μg/ml and IC₅₀ = 0.047 ± 0.0027 μg/ml, respective

SUBMITTER: Metwally NH 

PROVIDER: S-EPMC10999085 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature