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KMID : 0043320170400040469
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Archives of Pharmacal Research
2017 Volume.40 No. 4 p.469 ~ p.479
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Exploration of SAR for novel 2-benzylbenzimidazole analogs as inhibitor of transcription factor NF-κB
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Boggu Pulla Reddy
Venkateswararao Eeda
Manickam Manoj
Kim Young-Soo
Jung Sang-Hun
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Abstract
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A novel series of 2-benzylbenzimidazole analogs was designed, synthesized and investigated for their in vitro activities against LPS induced NF-κB inhibition in RAW 264.7 cells using the SEAP assay. Among them, 4-((4-(cyclohexylmethoxy)-1H-benzo[d]imidazol-2-yl)methyl)phenol (6e, >100% inhibition at 30 μM, IC50 = 3.0 μM), 4-((5-(cyclohexylmethoxy)-1H-benzo[d]imidazol-2-yl)methyl)phenol (6j, 96% inhibition at 30 μM, IC50 = 4.0 μM) and 2-((4-(cyclohexylmethoxy)-1H-benzo[d]imidazol-2-yl)methyl)phenol (6k, 95% inhibition at 30 μM, IC50 = 5.0 μM) showed strong inhibitory activity. The structure activity relationship confirmed that the substitution on benzimidazole ring A with hydrophobic cyclohexylmethoxy group at position 4 or 5 markedly enhances the activity. In addition, the hydrophilic hydrogen bonding donor group (OH) at position 2 or 4 on phenyl ring B connected with one methylene spacer to the benzimidazole ring is favorable for the inhibitory activity. However, hydrophobic (?OCH3 and ?Cl) groups on phenyl ring B decrease the activity.
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KEYWORD
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2-Benzylbenzimidazole, LPS, NF-κB inhibitor
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