Conjugation of Benzylvanillin and Benzimidazole Structure Improves DNA Binding with Enhanced Antileukemic Properties
| Autor: | Amin Malik Shah Abdul Majid, Shah Kamal Khan Jamal Din, Aman Shah Abdul Majid, Dan Ji, Shih Hsun Chen, Hasnah Osman, Po-Huang Liang, Ban A. Al-Mudarris, Zena A. Al-Mudaris |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Benzimidazole
HL60 Stereochemistry lcsh:Medicine Quantitative Structure-Activity Relationship Antineoplastic Agents Apoptosis DNA Fragmentation chemistry.chemical_compound Inhibitory Concentration 50 Cell Line Tumor Humans lcsh:Science Cell Proliferation Multidisciplinary Binding Sites lcsh:R Benzenesulfonates DNA Neoplasm Binding constant Caspase 9 G2 Phase Cell Cycle Checkpoints Molecular Docking Simulation chemistry Biochemistry Benzaldehydes Drug Design Cancer cell Nucleic acid DNA fragmentation lcsh:Q Benzimidazoles Pharmacophore Hydrophobic and Hydrophilic Interactions DNA Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 11, p e80983 (2013) |
| ISSN: | 1932-6203 |
| Popis: | Benzyl-o-vanillin and benzimidazole nucleus serve as important pharmacophore in drug discovery. The benzyl vanillin (2-(benzyloxy)-3-methoxybenzaldehyde) compound shows anti-proliferative activity in HL60 leukemia cancer cells and can effect cell cycle progression at G2/M phase. Its apoptosis activity was due to disruption of mitochondrial functioning. In this study, we have studied a series of compounds consisting of benzyl vanillin and benzimidazole structures. We hypothesize that by fusing these two structures we can produce compounds that have better anticancer activity with improved specificity particularly towards the leukemia cell line. Here we explored the anticancer activity of three compounds namely 2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2MP, N-1-(2-benzyloxy-3-methoxybenzyl)-2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2XP, and (R) and (S)-1-(2-benzyloxy-3-methoxyphenyl)-2, 2, 2-trichloroethyl benzenesulfonate, 3BS and compared their activity to 2-benzyloxy-3-methoxybenzaldehyde, (Bn1), the parent compound. 2XP and 3BS induces cell death of U937 leukemic cell line through DNA fragmentation that lead to the intrinsic caspase 9 activation. DNA binding study primarily by the equilibrium binding titration assay followed by the Viscosity study reveal the DNA binding through groove region with intrinsic binding constant 7.39 µM/bp and 6.86 µM/bp for 3BS and 2XP respectively. 2XP and 3BS showed strong DNA binding activity by the UV titration method with the computational drug modeling showed that both 2XP and 3BS failed to form any electrostatic linkages except via hydrophobic interaction through the minor groove region of the nucleic acid. The benzylvanillin alone (Bn1) has weak anticancer activity even after it was combined with the benzimidazole (2MP), but after addition of another benzylvanillin structure (2XP), stronger activity was observed. Also, the combination of benzylvanillin with benzenesulfonate (3BS) significantly improved the anticancer activity of Bn1. The present study provides a new insight of benzyl vanillin derivatives as potential anti-leukemic agent. |
| Databáze: | OpenAIRE |
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