N-formylpyrazolines and N-benzoylpyrazolines as potential inhibitors cathepsin L

S. Garg; N. Raghav; S. Garg; N. Raghav

doi:10.3934/molsci.2016.3.454

AIMS Molecular Science

2016, Volume 3, Issue 3: 454-465. doi: 10.3934/molsci.2016.3.454

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Research article

N-formylpyrazolines and N-benzoylpyrazolines as potential inhibitors cathepsin L

S. Garg ,
N. Raghav ^,

Department of Chemistry, Kurukshetra University, Kurukshetra-136119, India

Received: 26 May 2016 Accepted: 22 August 2016 Published: 25 January 2016

Elevated levels of cathepsins implicated in cancer, inflammation and number of degenerative diseases emphasize the investigation of potential inhibitors in search for novel chemotherapeutic agents with better efficacy. Along with other cathepsins, cathepsin L has emerged out as a potential drug target in these diseased conditions. In the present study, we have assayed the inhibitory potency of two structurally related series of substituted N-formylpyrazolines and N-benzoylpyrazolines as inhibitors to cathepsin L. SAR studies show that N-formylpyrazolines were better inhibitors than N-benzoylpyrazolines. The most potent inhibitors among the two series were nitro substituted compounds 1i and 2i with K_ivalues of ~6.4 × 10⁻¹⁰ and 5.7 × 10⁻⁹M for cathepsin L, respectively. The inhibitory potential of the compounds have been found comparative to the specific inhibitor, leupeptin. Docking experiments showing interaction between N-formylpyrazolines, N-benzoylpyrazolines and cathepsin L active site also provided useful insights.
- N-formylpyrazolines,
- N-benzoylpyrazolines,
- cathepsin L inhibitors,
- endogenous proteolysis
Citation: S. Garg, N. Raghav. N-formylpyrazolines and N-benzoylpyrazolines as potential inhibitors cathepsin L[J]. AIMS Molecular Science, 2016, 3(3): 454-465. doi: 10.3934/molsci.2016.3.454

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Abstract

Elevated levels of cathepsins implicated in cancer, inflammation and number of degenerative diseases emphasize the investigation of potential inhibitors in search for novel chemotherapeutic agents with better efficacy. Along with other cathepsins, cathepsin L has emerged out as a potential drug target in these diseased conditions. In the present study, we have assayed the inhibitory potency of two structurally related series of substituted N-formylpyrazolines and N-benzoylpyrazolines as inhibitors to cathepsin L. SAR studies show that N-formylpyrazolines were better inhibitors than N-benzoylpyrazolines. The most potent inhibitors among the two series were nitro substituted compounds 1i and 2i with K_ivalues of ~6.4 × 10⁻¹⁰ and 5.7 × 10⁻⁹M for cathepsin L, respectively. The inhibitory potential of the compounds have been found comparative to the specific inhibitor, leupeptin. Docking experiments showing interaction between N-formylpyrazolines, N-benzoylpyrazolines and cathepsin L active site also provided useful insights.

References

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