Abstract
Aim:Simultaneous inhibition of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) may enhance anti-HCV effects and reduce resistance and side effects.Results/methodology:Novel hybrid derivatives were designed and synthesized to exhibit dual activity against HCV and its associated major complication, HCC. The synthesized compounds were screened for their potential activity against HCV and HCC. Compounds 5f, 5j, 5l, 5p, 5q, 5r, 6c and 6d exhibited potential in vitro anticancer activity against HCC cell line HepG2, while compounds 5a, 5l, 5p and 5v showed in vitro anti-HCV activity. Docking studies suggested that the newly synthesized compounds could suppress HCC through VEGFR2 tyrosine kinase inhibition.Conclusion:Compounds 5l and 5p exhibited dual activity against HCV and HCC in vitro.
Highlights
Biological screening results revealed that compounds 5f, 5j, 5l, 5p, 5q, 5r, 6c and 6d exhibited potential in vitro anticancer activity against hepatocellular carcinoma (HCC) cell line HepG2, while compounds 5a, 5l, 5p and 5v showed in vitro anti-hepatitis C virus (HCV) activity against HepG2 cells infected with HCV
Conclusion & future perspective Molecular hybridization is an important concept in drug design based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity, selectivity and efficacy and reduced undesired side effects, when compared with the parent drugs
The disease can be a mild illness lasting a few weeks or a serious, lifelong condition that can lead to liver cirrhosis which can progress to HCC
Summary
Chemistry The target compounds were prepared (Figure 4) through the reaction of 2-acetylbenzofuran or 2-acetyl benzimidazole with substituted thiosemicarbazides in ethanol containing few drops of glacial acetic acid as a catalyst [39,40] to yield the corresponding thiosemicarbazones, which were cyclized using chloroacetic acid and anhydrous sodium acetate in glacial acetic acid [39,41] to give the key intermediates, 4-thiazolidinones. The 1H-NMR spectra of the unexpected future science group www.futuremedicine.com products obtained from the benzimidazole or benzofuran derivatives lacked the aromatic protons of benzimidazole or benzofuran, the singlet corresponding to -N = C-CH3 at 2.23–2.60 p.p.m. and the deuterium exchangeable singlet corresponding to N-H of benzimidazole at 11.22–12.56 p.p.m. In addition, the unexpected compounds retained the singlet at 3.94–4.14 p.p.m. attributed to thiazolidinone C5-H2 and both were characterized by the appearance of two singlets at 8.30–8.50 and 8.80–8.95 p.p.m. assigned for -CH = N-N = and pyrazole C5-H, respectively. The results revealed that four compounds 5a, 5l, 5p and 5v exhibited in vitro anti-HCV activity, as indicated by the disappearance of the band corresponding to the fragment of 174 base pairs length (Figure 7) These compounds inhibited the virus replication at concentrations ranging from 5.10 to 13.80 μg/ml. The benzimidazole derivatives substituted by 2-oxoindolin-3-ylidene were found to be less potent than their 1,3-diaryl-1H-pyrazole analogs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
