Four new carbazole alkaloids from Murraya koenigii that display anti-inflammatory and anti-microbial activities

• Published in: Organic & biomolecular chemistry 2016-01, Vol.14 (12), p.3322-3332
• Main Authors: Nalli, Yedukondalu, Khajuria, Vidushi, Gupta, Shilpa, Arora, Palak, Riyaz-Ul-Hassan, Syed, Ahmed, Zabeer, Ali, Asif
• Format: Article
• Language: English
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Alkaloids - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Bacillus cereus - drug effects; Candida albicans - drug effects; Carbazoles - chemical synthesis; Carbazoles - chemistry; Carbazoles - pharmacology; Dose-Response Relationship, Drug; Escherichia coli - drug effects; Humans; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - biosynthesis; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Microbial Sensitivity Tests; Molecular Structure; Murraya - chemistry; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c6ob00267f

In our present study, four new, designated as murrayakonine A-D (), along with 18 known carbazole alkaloids were isolated from CHCl3 : MeOH (1 : 1) crude extracts of the stems and leaves of Murraya koenigii (Linn.) Spreng. The structures of the all isolated compounds were characterized by analysis of HR-ESI-MS and NMR (1D and 2D spectroscopy) results, and comparison of their data with the literature data. For the first time, all the isolates were evaluated for their anti-inflammatory activities, using both in vitro and in vivo experiments, against the key inflammatory mediators TNF-α and IL-6. The new compound murrayakonine A (), O-methylmurrayamine A () and murrayanine () were proven to be the most active, efficiently inhibiting TNF-α and IL-6 release in a dose-dependent manner and showing decreased LPS induced TNF-α and IL-6 production in human PBMCs [corrected]. Furthermore, all the isolates were screened for their antimicrobial potential, and the compounds girinimbine () (IC50 3.4 μM) and 1-hydroxy-7-methoxy-8-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde () (IC50 10.9 μM) displayed potent inhibitory effects against Bacillus cereus. Furthermore, compounds murrayamine J () (IC50 11.7 μM) and koenimbine () (IC50 17.0 μM) were active against Staphylococcus aureus. However, none of the compounds were found to be active against Escherichia coli or Candida albicans.