Synthesis of Polyfunctionalized Fused Pyrazolo‐Pyridines: Characterization, Anticancer Activity, Protein Binding and Molecular Docking Studies

Abstract

The reaction of a multi-substituted pyrazole 1 with aryl or heteroaryl aldehydes and active methylene compounds afford unexpected pyrazolo[1,5-a]pyridine derivatives 4(a-k). Mechanism for this unexpected reaction involving reactivity of the active methylene moiety with a neighboring endocyclic NH group is proposed and structure has been established by the NMR and single crystal X-ray diffraction studies. Moreover, all the newly synthesized compounds were tested for their anticancer activity against sixty human cell lines at NCI. Among all the compounds, three scaffolds 4d, 4 h and 4k showed enhancement in anticancer activity in comparison with remaining synthesized compounds. Interestingly compound 4k was found to highly active even at a five dose concentration. The IC 50 values were determined against two cell lines MCF-7 and HepG2, the results obtained have shown promising effects against cancer cell lines. Further, the molecular docking studies revealed that substituted pyrazolo[1,5-a]pyridine derivatives are good candidates in the medicinal field.

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

“…A novel series of pyrazol [1,5- a ]pyridine derivatives were prepared and evaluated for their antiproliferative activity against 60 human cancer cell lines by Naik et al at the National Cancer Institute (NCI) [ 118 ]. In vitro anticancer assays showed that derivative 99 exhibited remarkable broad-spectrum inhibitory activity against most tested cell lines with GI 50 values ranging from 1.18 to 8.18 µM.…”

Synthesis and Cytotoxic Activity of Arenecarbaldehyde 2-Pyridinylhydrazone Derivatives

“…[4][5][6] The examples of pyridine compounds being studied include metal complexes, [7,8] imidazolyl-pyridine, [9,10] and pyrazolyl-pyridine derivatives. [11] Cl The great majority of antitumor drugs are usually related to an elevated number of non-specific toxicities, thus we urgently need more efficient and selective chemotherapeutics compounds to treat cancer. [12] The hydrazonyl functional group, CH=N-NH, readily formed from hydrazines and arenecarbaldehydes, is found in many compounds with a wide range of pharmacological activities, including antibacterial, antifungal, anticonvulsant, anti-inflammatory, antimalarial, antitubercular, and anti-cancer activities.…”