Background:
Cancer being a deadly disease, many reports of new chemical entities are
available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly
as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we
decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive
study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism
of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the
present study intends to accomplish.
Methods:
Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly
multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to
Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of
the most active ones. Then, the compound exhibiting the best activity was docked against human CHK-
1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of
the PPZs.
Results:
The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave
assisted synthesis and other methods. Among the synthesized compounds, most compounds
showed moderate to good anticancer activity against the MTT assay. After performing the absorbance
studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to
DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino
substituted moiety) clearly showed good binding affinities as predicted by our experimental
findings.
Conclusion:
The paper describes a comprehensive synthesis, in-vitro and docking studies done on new
PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic
activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to
the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental
results. Thus, these new molecules appear to be potential anticancer agents, but further studies
are required to substantiate and elaborate on these findings.
in silico-Based Virtual Screening and Molecular Docking Analysis of
Phytochemicals obtained from Methanolic Extract of Cleome viscosa
Linn. by GC-MS Method for its Anticancer Activity
