Melokhanines A–J, Bioactive Monoterpenoid Indole Alkaloids with Diverse Skeletons fromMelodinus khasianus

Abstract

The new melokhanines A-J (1-10) and 22 known (11-32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid. Melokhanines B-H (2-8) possess a new 6/5/5/6/6 pentacyclic indole alkaloid skeleton. Alkaloids 1-16, 25-27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa (MIC range 2-22 μM). Among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi (MIC range 38-150 μM), i.e., half the efficacy of the positive control, griseofulvin.

Acute and Sub-Acute Toxicological Evaluations of Bioactive Alkaloidal Extract from Melodinus henryi and Their Main Chemical Constituents

“…In this study, 15 monoterpenoid indole alkaloids were isolated and identified. According to the structural characteristics, the compounds were classified as strychnos-type alkaloids (1-3), aspidosperma-type alkaloids (4)(5)(6)(7)(8), condylocarpan-type alkaloid (9), eburna-type alkaloids (10)(11), and quinoline-type alkaloids (12)(13)(14)(15). Previous reports on the cytotoxic activities of the compounds showed that aspidosperma-type alkaloids 4, 5, 6 and 8 had significant cytotoxic activities on human cancer cell lines, while other types of compounds have no obvious cytotoxic activity [13,19].…”

“…Alkaloid is one of the most important classes of plant natural products with a large range of therapeutic properties, including anti-depressant, immunosuppressive, antimicrobial, anti-inflammatory, anti-tumor, etc. [4][5][6]. Some of which have been developed as clinical drugs to treat a variety of illnesses [7].…”

Synthesis of N‐Fused Seven‐Membered Indoline‐3‐ones via a Palladium‐Catalyzed One‐Pot Insertion Reaction from 2‐Alkynyl Arylazides and Cyclic β‐Diketones

“…Indolin‐3‐ones with a N ‐fused ring as an important kind of heterocycles have unique biological and pharmaceutical activities which exist as core scaffold in a number of natural products, such as (–)‐isatisine A, (–)‐melokhanine E, fluorocarpamine (Figure ). Thus, the methods for the synthesis of indolin‐3‐ones containing a N ‐fused ring have been reported extensively Among those reported reactions, the substituted 2‐aryl‐3 H ‐indol‐3‐ones G were used as the key substrates, which could be attacked easily by various nucleophilic reagents.…”

Stereocontrolled Synthesis of Melokhanine E via an Intramolecular Formal [3+2] Cycloaddition

“…Within the family, melokhanine E is of particular interest due to its superior, broad-spectrum activity (MIC = 2 µM against P. aeruginosa and 5 µM against E. faecalis). 4 A key structural motif of the melokhanines is a core piperidine heterocycle bearing C3 quaternary substitution. This structural element is found in an array of bioactive natural products and represents a significant synthetic challenge (2-5, Figure 1).…”

“…With the natural product in hand, we next sought to confirm the biological activity reported in Luo and coworkers' isolation report. 4 In the isolation report, Luo and coworkers report impressive antibiotic against gram-negative bacteria (P. aeruginosa MIC 2 µM, 0.78 µg/mL) as well as gram-positive bacteria (E. faecalis MIC 5 µM, 1.56 µg/mL). We explored the activity of 1 against both the pathogens reported in the isolation report as well as the ATCC numbers reported 22 and found in all cases the activity of the natural product was > 256 µg/mL.…”