Synthesis of novel derivatives of murrayafoline A and their inhibitory effect on LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells

Abstract

A series of N-substituted-1,2,3-triazole murrayafoline A derivatives were successfully synthesized using click azide-alkyne Huisgen cycloaddition reaction between 1-methoxy-3-methyl-9-(3-azido)-propyl-9H-carbazole and substituted alkynes. Their chemical structures were confirmed by (1)H, (13)C NMR and HR-ESI-MS spectral data. In addition, the interested effects on LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells of synthetic murrayafoline A derivatives were also investigated. Our results indicated that murrayafoline A derivatives containing 1,2,3-triazole nucleus potentially possessed anti-inflammatory action through inhibiting production of IL-6, IL-12 p40 and TNF-α.

Fischer indole synthesis applied to the total synthesis of natural products

“…80,81 Murrayafoline A 82, extracted from the root of various species of the genus Glycosmis, Murraya and Clausena (Rutaceae), displays potent fungicidal property against Cladosporium cucumerinum and growth inhibitory property on cell cycle Mphase inhibitory, human brosarcoma HT-1080 cells and apoptosis inducing properties on mouse tsFT210 cells. 82 In 1998, Murakami and co-workers described the six-step total synthesis of murrayafoline A 82 with 40% yield. 83 The current method initiated by the treatment of aminophenol 83 through the 2-hydrazino-5-methylphenol 84 to give the Omethanesulfonyl (mesyl) derivative 86.…”

Synthesis and Cytotoxic Activity Evaluation of Novel Derivatives of Murrayafoline A

“…Compound 2 was synthesized from murrayafoline A according to the procedure as described in reference [9].…”

“…This carbazole was reported to show significant growth suppression of the human leukemia cell line HL-60 due to apoptosis mediated by the activation of the caspase-9/caspase-3 pathway [7] and prevent heart diseases [8]. Recently, some of the N-substituted derivatives were synthesized and evaluated the anti-inflamamtory activity [9]. However, no reports on the synthesis and biological evaluation of conjugates between murrayfoline A and other bioactive compounds are available.…”

Synthesis of Triazole Derivatives of 9‐Ethyl‐9H‐carbazole and Dibenzo[b,d]furan and Evaluation of Their Antimycobacterial and Immunomodulatory Activity

“…Two more carbazole‐triazole derivatives XIV‐A and XIV‐B exhibited promising anti‐tubercular activity (MIC: 6.25 μ g/mL) with low cytotoxicity . N ‐substituted 1,2,3‐triazole derivative XV inhibited the production of inflammatory cytokines like IL‐12 p40, IL‐6, and TNF‐ α at a concentration of 12.5 μM while 1,2,4‐triazolium salt of N ‐substituted carbazole XVI (Figure ) demonstrated excellent antibacterial and antifungal activity . In the same way, dibenzo[b,d]furan‐triazole derivatives XVIIA‐C (MIC = 6.25 μg/mL) and XVIII (MIC = 0.78 μg/mL) exhibit antimycobacterial activity against M. tuberculosis with low cytotoxicity.…”