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A novel approach towards design, synthesis and evaluation of some Schiff base analogues of 2-aminopyridine and 2-aminobezothiazole against hepatocellular carcinoma.

Abstract
Hepatocellular carcinoma is the most common primary malignancy of the liver with poor prognosis. In this study novel, Schiff's bases of 2-aminopyridine (SSSC-26 to 31) and 2-aminobenzothiazole (SSSC-32 to 37) were designed, synthesised and evaluated for antioxidant potential using DPPH method, and anti-hepatocellular carcinoma property using diethylnitrosamine (DEN) induced hepatocellular carcinoma rat model. The in-silico pharmacokinetic, rule of five and toxicity studies reveals that all the leads have an excellent intrinsic quality and sufficient structural features necessary for an oral activity. Molecular docking studies of all compounds into the ligand binding pocket of checkpoint kinase1 and vascular endothelial growth factor receptor-2 was also performed using Schrodinger software suite v8.5, and which have shown good Glide scores. Further compounds were synthesised based on the docking score and ADMET profile. The 1,1-diphenyl-2-picrylhydrazil (DPPH) scavenging study was carried out, and results showed that SSSC-29 (IC50-63.60) and SSSC-33 (IC50-60.32) were having good anti-oxidant potential in comparison with ascorbic acid (IC50-55.27). SSSC-33 further evaluated for anti-cancer potential against diethylnitrosamine (200mg/kg bw) induced hepatocellular carcinoma in rats. The biochemical, histopathological and morphological data showed that SSSC-33 can reverse the changes occurred in the cancerous liver significantly. All these findings suggested that SSSC-33-((benzo[d]thiazol-2-ylimino) methyl)phenol) could be a potential compound in combating the oxidative damage of hepatic cells occurred due to the development of hepatocellular carcinoma induced by a chemical carcinogen, DEN.
AuthorsShinu Chacko, Subir Samanta
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 89 Pg. 162-176 (May 2017) ISSN: 1950-6007 [Electronic] France
PMID28222397 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Aminopyridines
  • Antineoplastic Agents
  • Antioxidants
  • Benzothiazoles
  • Biphenyl Compounds
  • Carcinogens
  • Free Radical Scavengers
  • Picrates
  • Schiff Bases
  • aminobenzothiazole compound
  • Diethylnitrosamine
  • 1,1-diphenyl-2-picrylhydrazyl
  • alpha-aminopyridine
Topics
  • Aminopyridines (chemical synthesis, pharmacokinetics, pharmacology)
  • Animals
  • Antineoplastic Agents (chemical synthesis, pharmacokinetics, pharmacology)
  • Antioxidants (pharmacology)
  • Benzothiazoles (chemical synthesis, pharmacokinetics, pharmacology)
  • Biphenyl Compounds
  • Carcinogens
  • Diethylnitrosamine
  • Drug Design
  • Free Radical Scavengers (pharmacology)
  • Liver (pathology)
  • Liver Neoplasms, Experimental (chemically induced, drug therapy, prevention & control)
  • Male
  • Models, Molecular
  • Molecular Docking Simulation
  • Picrates
  • Rats
  • Rats, Wistar
  • Schiff Bases (chemical synthesis, pharmacokinetics, pharmacology)

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