当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis, binding assays, cytotoxic activity and docking studies of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor.

Synthesis, binding assays, cytotoxic activity and docking studies of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor.

Abstract：

:Herein we report the design, synthesis, bioinformatic and biological studies of benzimidazole and benzothiophene derivatives as new cannabinoid receptor ligands. To test the hypothesis that the lack of a hydrogen bond interaction between benzimidazole and benzothiophene derivatives with Lys192 reduces their affinity for CB1 receptors (as we previously reported) and leads to CB2 selectivity, most of the tested compounds do not exhibit hydrogen bond acceptors. All compounds displayed mostly CB2 selectivity, although this was more pronounced in the benzimidazoles derivatives. Furthermore, docking assays revealed a ∏-cation interaction with Lys109 which could play a key role for the CB2 selectivity index. The series displayed low toxicity on five different cell lines. Derivative 8f presented the best binding profile (Ki = 0.08 μM), high selectivity index (KiCB1/KiCB2) and a low citoxicity. Interestingly, in cell viability experiments, using HL-60 cells (expressing exclusively CB2 receptors), all synthesised compounds were shown to be cytotoxic, suggesting that a CB2 agonist response may be involved.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Romero-Parra J,Mella-Raipán J,Palmieri V,Allarà M,Torres MJ,Pessoa-Mahana H,Iturriaga-Vásquez P,Escobar R,Faúndez M,Di Marzo V,Pessoa-Mahana CD

doi

10.1016/j.ejmech.2016.08.005

subject

Has Abstract

pub_date

2016-11-29 00:00:00

pages

17-35

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)30648-1

journal_volume

124

pub_type

杂志文章

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