Khanit Suwanborirux

Vobasinyl‐iboga bisindole alkaloids, potent acetylcholinesterase inhibitors from Tabernaemontana divaricata root

The roots of the Thai medicinal plant, Tabernaemontana divaricata (L.) R. Br. ex Roem. & Schult., were investigated for their content of acetylcholinesterase inhibitors. Bioassay‐guided fractionation using the Ellman colorimetric method led to the isolation of two bisindole alkaloids, 19,20‐dihydrotabernamine and 19,20‐dihydroervahanine A. The compounds showed higher inhibitory activity on acetylcholinesterase in comparison with galanthamine, a well‐known acetylcholinesterase inhibitor. The inhibitory activity of 19,20‐dihydroervahanine A was proved to be specific, reversible and competitive. During the separation process, two inactive bisindole alkaloids, conodurine and tabernaelegantine A, were also isolated. The data suggest that the substitutions at the carbons 11′, 12′ and 16′ might affect the acetylcholinesterase inhibitory activity.

Acetylcholinesterase-inhibiting activity of pyrrole derivatives from a novel marine gliding bacterium, Rapidithrix thailandica.

Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix thailandica, was assessed (IC50 4.9 μM). Two related pyrrole derivatives, 3-(2′-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4), were also isolated from two other strains of R. thailandica. The isolation of 3 from a natural source is reported here for the first time. Compound 4 was proposed to be an isolation artifact derived from 3. The two isolated compounds were virtually inactive in the acetylcholinesterase-inhibitory assay (enzyme inhibition < 30% at 0.1 g L−1).

Screening for phosphodiesterase inhibitory activity of Thai medicinal plants

INTRODUCTION Phosphodiesterases (PDEs) are a group of enzymes that have powerful effects on cellular signaling because they regulate the second messenger, cAMP or cGMP. PDE inhibitors have been used for treatment of many indications such as cardiovascular diseases, chronic obstructive pulmonary diseases, erectile dysfunction and pulmonary hypertension. THE AIM OF THE STUDY The aim of the study was to search for sources of PDE inhibitors from Thai biodiversity. MATERIALS AND METHODS Some Thai medicinal plants used as aphrodisiac and neurotonic agents together with plants from Leguminosae collected from the North of Thailand were screened for PDE inhibitory activity using a radioassay. RESULTS Seven from nineteen aphrodisiac and neurotonic plants as well as three from twelve Leguminosae plants showed potent PDEs inhibitory activity. The concentrations that could inhibit 50% PDE activity (IC(50)) of the active extracts were determined in comparison to the standard inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Betula alnoides, Hiptage benghalensis, Leea indica and Senna surrattensis showed IC(50) values in the range of microgram per milliliter while IBMX standard showed an IC(50) value of 0.68+/-0.13 microg/ml. CONCLUSION Thai biodiversity was the great sources of PDE inhibitors.

Petrosamine, a potent anticholinesterase pyridoacridine alkaloid from a Thai marine sponge Petrosia n. sp

Two pyridoacridine alkaloids, including a known petrosamine and a new 2-bromoamphimedine were isolated from a Thai marine sponge Petrosia n. sp. The alkaloids were characterized on the basis of 1D and 2D NMR, MS, and IR spectroscopy. Only petrosamine showed strong acetylcholinesterase inhibitory activity approximately six times higher than that of the reference galanthamine. A computational docking study of petrosamine with the enzyme from the electric eel Torpedo californica (TcAChE) showed the major contribution to the petrosamine-TcAChE interaction to be arising from the quaternary ammonium group of petrosamine.

Kaempferia parviflora, a plant used in traditional medicine to enhance sexual performance contains large amounts of low affinity PDE5 inhibitors

AIM OF THE STUDY A number of medicinal plants are used in traditional medicine to treat erectile dysfunction. Since cyclic nucleotide PDEs inhibitors underlie several current treatments for this condition, we sought to show whether these plants might contain substantial amounts of PDE5 inhibitors. MATERIALS AND METHODS Forty one plant extracts and eight 7-methoxyflavones from Kaempferia parviflora Wall. ex Baker were screened for PDE5 and PDE6 inhibitory activities using the two-step radioactive assay. The PDE5 and PDE6 were prepared from mice lung and chicken retinas, respectively. All plant extracts were tested at 50 μg/ml whereas the pure compounds were tested at 10 μM. RESULTS From forty one plant extracts tested, four showed the PDE5 inhibitory effect. The chemical constituents isolated from rhizomes of Kaempferia parviflora were further investigated on inhibitory activity against PDE5 and PDE6. The results showed that 7-methoxyflavones from this plant showed inhibition toward both enzymes. The most potent PDE5 inhibitor was 5,7-dimethoxyflavone (IC(50) = 10.64 ± 2.09 μM, selectivity on PDE5 over PDE6 = 3.71). Structure activity relationship showed that the methoxyl group at C-5 position of 7-methoxyflavones was necessary for PDE5 inhibition. CONCLUSIONS Kaempferia parviflora rhizome extract and its 7-methoxyflavone constituents had moderate inhibitory activity against PDE5. This finding provides an explanation for enhancing sexual performance in the traditional use of Kaempferia parviflora. Moreover, 5,7-dimethoxyflavones should make a useful lead compound to further develop clinically efficacious PDE5 inhibitors.

Actinaurispora siamensis gen. nov., sp. nov., a new member of the family Micromonosporaceae.

Two actinomycete strains, CM2-8(T) and CM2-12, were isolated from temperate peat swamp forest soil in Chiang Mai Province, Thailand. Their taxonomic positions were determined using a polyphasic approach. Chemotaxonomic characteristics of these strains coincided with those of the family Micromonosporaceae, i.e. cell wall chemotype II, N-glycolyl type of muramic acid, and type II phospholipids. Phylogenetic analysis based on 16S rRNA gene sequence data also indicated that these strains fell within the family Micromonosporaceae and formed a distinct taxon in the Micromonosporaceae phylogenetic tree. On the basis of phylogenetic analysis, characteristic patterns of 16S rRNA gene signature nucleotides and chemotaxonomic data, it is proposed that the novel isolates belong to a new genus, Actinaurispora gen. nov. The type species of the genus is proposed as Actinaurispora siamensis sp. nov., with strain CM2-8(T) (=JCM 15677(T)=BCC 34762(T)) as the type strain.

Bisindole alkaloids and secoiridoids from Alstonia macrophylla Wall. ex G. Don

The ethanolic extract from stems of a Thai medicinal plant, Alstonia macrophylla Wall. ex G. Don (Apocynaceae) showed a significant inhibitory effect on acetylcholinesterase (AChE) determined by using Ellman assay. Four compounds i.e., a bisindole alkaloid, macralstonine (1), a new bisindole alkaloid, thungfaine (2), a secoiridoid glycoside, sweroside (3) and a new secoiridoid glycoside, naresuanoside (4) were isolated. Compound 4 showed moderate AChE and butyrylcholinesterase (BChE) inhibitory effects. Interestingly, compound 4 inhibited cell growth on human androgen-sensitive prostate cancer cell line (LNCaP) but no effect on viability of human foreskin fibroblast cells (HF).

Micromonospora spongicola sp. nov., an actinomycete isolated from a marine sponge in the Gulf of Thailand

An actinomycete strain, S3-1T, was isolated from marine sponge sample collected from the Gulf of Thailand. The strain is aerobic, Gram-positive and produced single spores at the tip of the substrate mycelium. Strain S3-1T contained meso-diaminopimelic acid in the peptidoglycan, whole-cell sugars were arabinose, galactose, glucose, rhamnose, ribose and xylose. The polar lipid profile of strain S3-1T consisted of phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, phosphoglycolipid and unknown polar lipids. Morphological and chemotaxonomic characteristics of the strain were identified as a member of the genus Micromonospora. Phylogenetic analysis based on 16S rRNA gene sequence analysis of the strain showed similarity to Micromonospora nigra DSM 43818T (98.8%), Micromonospora yangpuensis FXJ6.011T (98.7%) and Micromonospora narathiwatensis BTG4-1T (98.6%). The DNA G+C content was 72.7 mol%. The phenotypic characteristics and DNA–DNA relatedness values supported that the classification of this strain as a novel species in the genus Micromonospora, for which the name Micromonospora spongicola sp. nov. (type strain S3-1T =BCC 45595T=NBRC 108779T) is proposed.

Kabiramides J and K, trisoxazole macrolides from the sponge Pachastrissa nux.

Three trisoxazole macrolides possessing a 30-α,β-enone moiety, including the known kabiramide G (1) and the new kabiramides J (2) and K (3), were isolated from the sponge Pachastrissa nux, along with the previously reported kabiramides B (4), C (5), and D (6). To date, the enone moiety has been found to associate solely with the trisoxazole macrolides from P. nux. All of the isolated macrolides showed moderate to strong antimalarial and cytotoxic activities, except for 1, which possessed only potent cytotoxicity.

Streptomyces chumphonensis sp. nov., isolated from marine sediments.

Two actinomycete strains, KK1-2(T) and CPB4-7, were isolated from marine sediments collected in Chumphon province, Thailand. Chumphon province, Thailand. Their taxonomic positions were determined using a polyphasic approach. The morphological, cultural and chemotaxonomic characteristics of these isolates were consistent with the classification of the strains as representing a member of the genus Streptomyces. They contained LL-diaminopimelic acid in their cell wall peptidoglycan; the whole-cell sugars were ribose and glucose. The predominant menaquinones were MK9-(H6) and MK9-(H8). The major polar lipids were phosphatidylethanolamine, phosphatidylinositol, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol mannosides. The predominant cellular fatty acids were anteiso-C(15 : 0), iso-C(16 : 0) and iso-C(15 : 0). On the basis of 16S rRNA gene sequence similarity studies, these isolates were determined to be closely related to Streptomyces xinghaiensis JCM 16958(T) (98.2%), Streptomyces rimosus subsp. paromomycinus JCM 4541(T) (98.1%), Streptomyces sclerotialus JCM 4828(T) (98.1%) and Streptomyces flocculus JCM 4476(T) (98.0%). The G+C contents of the genomic DNA of strains KK1-2(T) and CPB4-7 were 73.3 and 74.2 mol%, respectively. They could be clearly distinguished from the related type strains by a low DNA-DNA relatedness and phenotypic differences. On the basis of these results, these strains represent a novel species of the genus Streptomyces, for which the name Streptomyces chumphonensis sp. nov. (type strain KK1-2(T) = JCM 18522(T) = TISTR 2106(T) = PCU 330(T)) is proposed.