Cinnamaldehyde hydrazone derivatives as potential cathepsin B inhibitors: parallel in-vitro investigation in liver and cerebrospinal fluid

The emergence of cathepsins as a potential target for anticancer drugs has led to extensive research in the development of their inhibitors. In the present study, we designed, synthesized, and characterized several cinnamaldehyde schiff bases employing diverse hydrazines, as potential cathepsin B in...

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Bibliographic Details
Published in:International journal of biological macromolecules 2024-06, Vol.272 (Pt 1), p.132684, Article 132684
Main Authors: Vashisth, Chanchal, Kaushik, Tushar, Vashisth, Naman, Raghav, Neera
Format: Article
Language:English
Subjects:
Acrolein - analogs & derivatives
Acrolein - chemistry
Acrolein - pharmacology
Animals
Catalytic Domain
Cathepsin B
Cathepsin B - antagonists & inhibitors
Cathepsin B - metabolism
Cinnamaldehyde
Docking
Humans
Hydrazones - chemical synthesis
Hydrazones - chemistry
Hydrazones - pharmacology
Liver - drug effects
Liver - metabolism
Molecular Docking Simulation
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Summary:The emergence of cathepsins as a potential target for anticancer drugs has led to extensive research in the development of their inhibitors. In the present study, we designed, synthesized, and characterized several cinnamaldehyde schiff bases employing diverse hydrazines, as potential cathepsin B inhibitors. The parallel studies on cathepsin B isolated from liver and cerebrospinal fluid unveiled the significance of the synthesized compounds as cathepsin B inhibitors at nanomolar concentrations. The compound, 7 exhibited the highest inhibition of 83.48 % and 82.96 % with an IC50 value of 0.06 nM and 0.09 nM for liver and cerebrospinal fluid respectively. The inhibitory potential of synthesized compounds has been extremely effective in comparison to previous reports. With the help of molecular docking studies using iGEMDOCK software, we found that the active site -CH2SH group is involved in the case of α-N-benzoyl-D, l-arginine-b-naphthylamide (BANA), curcumin 2, 3, 6, and 7. For toxicity prediction, ADMET studies were conducted and the synthesized compounds emerged to be non-toxic. The results obtained from the in vitro studies were supported with in silico studies. The synthesized cinnamaldehyde schiff bases can be considered promising drug candidates in conditions with elevated cathepsin B levels.
ISSN:0141-8130
1879-0003
1879-0003
DOI:10.1016/j.ijbiomac.2024.132684