New pentadienone oxime ester derivatives: synthesis and anti-inflammatory activity

Qin Li,Juping Zhang,Liu Zeng Chen,Jie Quan Wang,Hai Ping Zhou,Wen Jian Tang,Wei Xue,Xin Hua Liu

doi:10.1080/14756366.2017.1396455

Abstract

To develop novel anti-inflammatory agents, a series of new pentadienone oxime ester compounds were designed and synthesized. The structures were determined by IR, 1H NMR, 13 C NMR, and HRMS. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition against LPS-induced nitric oxide (NO) release in RAW 264.7 cell. Among them, compound 5j was found to be one of the most potent compounds in inhibiting NO and IL-6 (IC50 values were 6.66 µM and 5.07 µM, respectively). Preliminary mechanism studies show that title compound 5j could significantly suppress expressions of nitric oxide synthase, COX-2, and NO, IL-6 through Toll-like receptor 4/mitogen-activated protein kinases/NF-κB signalling pathway. These data support further studies to assess rational design of more efficient pentadienone oxime ester derivatives with anti-inflammatory activity in the future.

Highlights

The body immune response divided into innate and acquired immunity
Innate immunity do not have the capacity of discriminating between self and foreign pathogens through a family of evolutionarily conserved receptors known like the Toll-like receptors (TLRs)[2]
The results suggested that unsymmetrical form might possess greater biological profile compared to the symmetrical form[19–21]

Summary

Introduction

The body immune response divided into innate and acquired immunity. To cope fatal organisms, body must depend on immune response. Upon stimulation with LPS, TLR4 initiates a series of signalling cascades resulting in activation of NF-jB and mitogen-activated protein kinases (MAPK) to induce the release of pro-inflammatory cytokines[4]. 1H NMR (500 MHz, DMSO-d6, ppm) d 8.84 (d, J 1⁄4 5.2 Hz, 1H, PyH), 8.36 (t, J 1⁄4 7.3 Hz, 1H, ArH), 8.27 (d, J 1⁄4 7.7 Hz, 1H, ArH), 8.12–8.00 (m, 5H, ArH), 7.79 (m, 8H, ArH, PyH), 7.55–7.49 (m, 2H, Ar-CH1⁄4, Py-CH1⁄4), 7.48–7.42 (m, 1H, PyH), 7.23 (d, J 1⁄4 8.3 Hz 1H, Ar-C 1⁄4 CH), 7.13 (d, J 1⁄4 7.4 Hz, 1H, Py-C 1⁄4 CH), 5.43 (s, 2H, CH2).[13] C NMR (125 MHz, DMSO-d6, ppm) d 163.2, 160.9, 157.1, 150.6, 147.3, 145.5, 145.1, 143.0, 137.5, 134.2, 132.1, 130.1, 129.7, 129.4, 128.7, 128.4, 125.9, 125.5, 124.4, 123.9, 123.1, 121.9, 117.6, 5c (1E,3E,4E)-1–(4-chlorophenyl)-5–(2-(3-methylbenzyloxy)phenyl)penta1,4-dien-3-one O-nicotinoyl oxime, Yellow solids, yield, 48.2%, m.p. 1 2 7–129 C; IR (KBr, cmÀ1) max: 3101, 2837, 1749, 1590, 1489, 1419, 1343, 1236, 1081, 1015, 971, 915, 813, 777, 758.

Results

Conclusion