Background: PDE5A is a phosphodiesterase which specifically hydrolyzes the cGMP to GMP. It
takes part in several physiological and pathological pathways and is considered an important drug target. Currently,
PDE5 inhibitors (ex; Sildenafil, Tadalafil) available in the market are not only being used for the treatment
of erectile dysfunction but at the same time, they are also in clinical trials being investigated as anticancer
Materials & Methods: In this work, we have examined pyrazolo [4,3-c]quinolin-3-ones as PDE5A inhibitors.
Pyrazolo [4,3-c]quinolin-3-ones are the class of tricyclic heterocyclic derivatives having a variety of therapeutically
interesting drug candidates known for their anti-inflammatory, anti-viral, anti-anxiety and anti-cancer
activity. Therefore, synthetic methods providing access to pyrazolo [4, 3-c] quinolin-3-ones are immensely
valuable. Here, we are reporting a simple but efficient route for the synthesis of novel 8–morpholino-2-aryl –
2, 5-dihydro-3H-pyrazolo [4, 3-c] quinolin-3-one derivatives.
Results: Further, molecular docking studies of synthesized compounds with human PDE5A protein showed
that all the compounds exhibited good docking score in comparison with known inhibitors. In addition, all the
synthesized molecules were evaluated against HCT116 cell lines for their antitumor activity.
Conclusion: Among all the synthesized compounds, compound 5a, 5d, and 6e showed better cytotoxicity.
Thus, these derivatives can be studied as potential inhibitors of PDE5A.