Introduction of marine-derived Streptomyces sp. UTMC 1334 as a source of pyrrole derivatives with anti-acetylcholinesterase activity.

AIM: Alzheimer's disease (AD) is the most common cause of dementia. The acetylcholinesterase (AChE) inhibitors are the most viable therapeutic target for its symptomatic treatment. The present study was aimed at exploring anti-AChE metabolite producing marine Actinobacteria. METHODS AND RESULTS: Of 220 isolates, 34 Actinobacteria extracts were tested for the presence of AChE inhibitors. The obtained results showed that bacterial strain UTMC 1334, inhibited AChE activity in a dose-dependent manner (IC50  = 0·36 ± 0·019 mg ml-1 ). Based on anti-oxidant and cytotoxicity studies, the most potent extract was able to scavenge DPPH radicals with an IC50 value of 45·67 µg ml-1 with the least cytotoxicity. The GC-MS analysis demonstrated that the mentioned activities could be related to pyrrole-derived compounds as were found the predominant constituents in the extract. The most active extract belonged to the strain that shows 99·41% similarity with Streptomyces lateritius based on 16S rRNA gene sequencing. CONCLUSIONS: Our results show anti-AChE activity is prevalent in marine Actinobacteria, and even in rather comparable prevalence with the antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights that exploring new lead anti-AChE compounds may result in discovering novel adjuvant candidates with potency in the treatment of cognitive diseases such as AD.

Catechol alkenyls from Semecarpus anacardium: acetylcholinesterase inhibition and binding mode predictions.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Semecarpus anacardium L. f. (Anacardiaceae) are used in Ayurvedic medicine and also in Iranian Traditional Medicine for various indications, among those for retarding and treatment of dementia. AIM OF THE STUDY: The severity of Alzheimer's disease obviously correlates with a cholinergic deficit. In a screening for acetylcholinesterase (AChE) inhibitory activity, an extract from the fruit resin of Semecarpus anacardium was among the most active ones. Thus, the aim of this study was to isolate the active compounds and to investigate them in detail. Their binding mode to the active site of AChE was investigated by in silico docking experiments. MATERIALS AND METHODS: From a dichloromethane extract in an activity-guided fractionation the active compounds were isolated under use of different chromatographic techniques. Their structures were unambiguously identified by one and two-dimensional (1)H and (13)C NMR spectroscopy and mass spectrometry and their cholinesterase inhibitory activities were determined by a microplate assay. In order to compare the 3D active sites of AChE from Torpedo californica (TcAChE) and from Electrophorus electricus (EeAChE), three files from the Protein Data Bank (PDB) were used and for docking experiments, GOLD 3.1 software was employed. The concentrations of active compounds in the extract and the fruits were determined by HPLC analysis. RESULTS: The active compounds were determined as 1',2'-dihydroxy-3'-pentadec-8-enylbenzene (A) and 1',2'-dihydroxy-3'-pentadeca-8,11-dienylbenzene (B). Their IC(50) values in an in vitro assay on AChE inhibition were determined as 12 and 34 µg/mL, respectively, while they were not active in the inhibition of butyrylcholinesterase (BChE). In silico docking experiments showed a similar bioactivity for compounds A and B. The concentration of compounds A and B in the fruits was 1.85% and 1.88%, respectively. CONCLUSION: In the search for the active principle of the fruit resin of Semecarpus anacardium, compounds A and B were identified as two selective inhibitors for AChE versus BChE.