Background: Indole and pyrazoles are one of the prime structural units in the field of
medicinal chemistry and have been reported to exhibit a variety of biological activities specifically
anti-cancer. In view of their medicinal significance, we synthesized a conjugate of the two moieties
to get access to newer and potential anti-cancer agents.
Methods: Indolyl pyrazoles [3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-indole-3-carbon
yl)acrylonitriles] (4a-l) were synthesized by adopting simple and greener protocol and all the synthesized
derivatives were docked against Bcl-2 protein and the selected chemical moieties were
screened for their cytotoxicity by using the MTT assay.
Results: All the synthesized compounds were docked against BCL-2 protein in order to understand
their binding pattern. Among the 12 compounds docked, 4d, 4f, 4h, 4j, and 4l compounds exhibited
better protein binding interactions and the same were screened for their anti-cancer activity against
A549 (lung) cancer cell lines at a concentration of 100 μM using Doxorubicin as standard. Substitutions
such as N-benzyl, N-ethyl groups and halogen groups such as Br, Cl on indole ring showed
moderate activity against A-549 cell lines.
Conclusion: Among the 5 indolyl pyrazole derivatives screened, compounds 4h and 4j showed significantly
better activity with an IC50 of 33.12 and 34.24 μM, respectively. Further, structural tweaking
of the synthesized new chemical entities may lead to potential hit/lead-like molecules.