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5 results on '"Sumet Chongruchiroj"'

1. New insights into the neuroprotective and beta-secretase1 inhibitor profiles of tirandamycin B isolated from a newly found Streptomyces composti sp. nov.

Author

Thitikorn Duangupama, Jaturong Pratuangdejkul, Sumet Chongruchiroj, Pattama Pittayakhajonwut, Chakapong Intaraudom, Sarin Tadtong, Patcharawee Nunthanavanit, Weerasak Samee, Ya-Wen He, Somboon Tanasupawat, and Chitti Thawai

Subjects
Medicine, Science
Abstract

Abstract Tirandamycin (TAM B) is a tetramic acid antibiotic discovered to be active on a screen designed to find compounds with neuroprotective activity. The producing strain, SBST2-5T, is an actinobacterium that was isolated from wastewater treatment bio–sludge compost collected from Suphanburi province, Thailand. Taxonomic characterization based on a polyphasic approach indicates that strain SBST2-5T is a member of the genus Streptomyces and shows low average nucleotide identity (ANI) (81.7%), average amino-acid identity (AAI) (78.5%), and digital DNA-DNA hybridization (dDDH) (25.9%) values to its closest relative, Streptomyces thermoviolaceus NBRC 13905T, values that are significantly below the suggested cut-off values for the species delineation, indicating that strain SBST2-5T could be considered to represent a novel species of the genus Streptomyces. The analysis of secondary metabolites biosynthetic gene clusters (smBGCs) in its genome and chemical investigation led to the isolation of TAM B. Interestingly, TAM B at 20 µg/mL displayed a suppressive effect on beta-secretase 1 (BACE1) with 68.69 ± 8.84% inhibition. Molecular docking simulation reveals the interaction mechanism between TAM B and BACE1 that TAM B was buried in the pocket of BACE-1 by interacting with amino acids Thr231, Asp 228, Gln73, Lys 107 via hydrogen bond and Leu30, Tyr71, Phe108, Ile118 via hydrophobic interaction, indicating that TAM B represents a potential active BACE1 inhibitor. Moreover, TAM B can protect the neuron cells significantly (% neuron viability = 83.10 ± 9.83% and 112.72 ± 6.83%) from oxidative stress induced by serum deprivation and Aβ1–42 administration models at 1 ng/mL, respectively, without neurotoxicity on murine P19-derived neuron cells nor cytotoxicity against Vero cells. This study was reportedly the first study to show the neuroprotective and BACE1 inhibitory activities of TAM B.

Published
2023
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2. Garcinia mangostana L. Pericarp Extract and Its Active Compound α-Mangostin as Potential Inhibitors of Immune Checkpoint Programmed Death Ligand-1

Author

Sandar Naing, Nichawadee Sandech, Arnatchai Maiuthed, Sumet Chongruchiroj, Jaturong Pratuangdejkul, and Pattamapan Lomarat

Subjects
α-mangostin, xanthones, Garcinia mangostana L. pericarp extract, Clusiaceae, PD-L1, chemoprevention, Organic chemistry, QD241-441
Abstract

α-Mangostin, a major xanthone found in mangosteen (Garcinia mangostana L., Family Clusiaceae) pericarp, has been shown to exhibit anticancer effects through multiple mechanisms of action. However, its effects on immune checkpoint programmed death ligand-1 (PD-L1) have not been studied. This study investigated the effects of mangosteen pericarp extract and its active compound α-mangostin on PD-L1 by in vitro and in silico analyses. HPLC analysis showed that α-mangostin contained about 30% w/w of crude ethanol extract of mangosteen pericarp. In vitro experiments in MDA-MB-231 triple-negative breast cancer cells showed that α-mangostin and the ethanol extract significantly inhibit PD-L1 expression when treated for 72 h with 10 µM or 10 µg/mL, respectively, and partially inhibit glycosylation of PD-L1 when compared to untreated controls. In silico analysis revealed that α-mangostin effectively binds inside PD-L1 dimer pockets and that the complex was stable throughout the 100 ns simulation, suggesting that α-mangostin stabilized the dimer form that could potentially lead to degradation of PD-L1. The ADMET prediction showed that α-mangostin is lipophilic and has high plasma protein binding, suggesting its greater distribution to tissues and its ability to penetrate adipose tissue such as breast cancer. These findings suggest that α-mangostin-rich mangosteen pericarp extract could potentially be applied as a functional ingredient for cancer chemoprevention.

Published
2023
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3. Selective α3β4 Nicotinic Acetylcholine Receptor Ligand as a Potential Tracer for Drug Addiction

Author

Apinan Kanasuwan, Winnie Deuther-Conrad, Sumet Chongruchiroj, Jiradanai Sarasamkan, Chanisa Chotipanich, Opa Vajragupta, and Kuntarat Arunrungvichian

Subjects
Inorganic Chemistry, drug-seeking behavior monitoring, triazole, drug addiction, α3β4 Nicotinic acetylcholine receptor, quinuclidine, Organic Chemistry, General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications
Abstract

α3β4 Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, α3β4 nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, (S)-QND8 and (S)-T2, for the development of an α3β4 nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction. The preserved key features are a fluorine atom for radiotracer development and a p-hydroxyl motif for ligand-receptor binding affinity. Four (R)- and (S)-quinuclidine-triazole (AK1-AK4) were synthesized and the binding affinity, together with selectivity to α3β4 nAChR subtype, were determined by competitive radioligand binding assay using [3H]epibatidine as a radioligand. Among all modified compounds, AK3 showed the highest binding affinity and selectivity to α3β4 nAChR with a Ki value of 3.18 nM, comparable to (S)-QND8 and (S)-T2 and 3069-fold higher affinity to α3β4 nAChR in comparison to α7 nAChR. The α3β4 nAChR selectivity of AK3 was considerably higher than those of (S)-QND8 (11.8-fold) and (S)-T2 (294-fold). AK3 was shown to be a promising α3β4 nAChR tracer for further development as a radiotracer for drug addiction.

Published
2023
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4. In Silico Finding of Key Interaction Mediated α3β4 and α7 Nicotinic Acetylcholine Receptor Ligand Selectivity of Quinuclidine-Triazole Chemotype

Author

Opa Vajragupta, Jiradanai Sarasamkan, Kuntarat Arunrungvichian, Peter Brust, Sumet Chongruchiroj, and Gerrit Schüürmann

Subjects
Stereochemistry, Protein subunit, In silico, stereoselectivity, Article, Catalysis, lcsh:Chemistry, Inorganic Chemistry, chemistry.chemical_compound, Homology modeling, Physical and Theoretical Chemistry, α3β4 nAChR, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, chemistry.chemical_classification, quinuclidine, Organic Chemistry, General Medicine, Ligand (biochemistry), Computer Science Applications, Amino acid, α7 nAChR, Nicotinic acetylcholine receptor, lcsh:Biology (General), lcsh:QD1-999, chemistry, nervous system, Salt bridge, sense organs, Quinuclidine, anti-1,2,3-triazole
Abstract

The selective binding of six (S)-quinuclidine-triazoles and their (R)-enantiomers to nicotinic acetylcholine receptor (nAChR) subtypes &alpha, 3&beta, 4 and &alpha, 7, respectively, were analyzed by in silico docking to provide the insight into the molecular basis for the observed stereospecific subtype discrimination. Homology modeling followed by molecular docking and molecular dynamics (MD) simulations revealed that unique amino acid residues in the complementary subunits of the nAChR subtypes are involved in subtype-specific selectivity profiles. In the complementary &beta, 4-subunit of the &alpha, 4 nAChR binding pocket, non-conserved AspB173 through a salt bridge was found to be the key determinant for the &alpha, 4 selectivity of the quinuclidine-triazole chemotype, explaining the 47&ndash, 327-fold affinity of the (S)-enantiomers as compared to their (R)-enantiomer counterparts. Regarding the &alpha, 7 nAChR subtype, the amino acids promoting a however significantly lower preference for the (R)-enantiomers were the conserved TyrA93, TrpA149 and TrpB55 residues. The non-conserved amino acid residue in the complementary subunit of nAChR subtypes appeared to play a significant role for the nAChR subtype-selective binding, particularly at the heteropentameric subtype, whereas the conserved amino acid residues in both principal and complementary subunits are essential for ligand potency and efficacy.

Published
2020
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5. A novel diterpene agent isolated from Microbispora hainanensis strain CSR-4 and its in vitro and in silico inhibition effects on acetylcholine esterase enzyme

Author

Ya-Wen He, Sumet Chongruchiroj, Nantiya Bunbamrung, Jaturong Pratuangdejkul, Sarin Tadtong, Yang Qian, Vipaporn Sareedenchai, Pinidphon Prombutara, Pattama Pittayakhajonwut, and Chitti Thawai

Subjects
0301 basic medicine, Sequence analysis, 030106 microbiology, lcsh:Medicine, In Vitro Techniques, Molecular Dynamics Simulation, Microbiology, Article, Antioxidants, 03 medical and health sciences, chemistry.chemical_compound, Mice, Catalytic Domain, RNA, Ribosomal, 16S, Chlorocebus aethiops, Animals, Humans, Computer Simulation, lcsh:Science, Vero Cells, Phylogeny, chemistry.chemical_classification, Multidisciplinary, biology, Strain (chemistry), Molecular Structure, Drug discovery, lcsh:R, Active site, Acetylcholinesterase, Chemical biology, In vitro, Recombinant Proteins, Amino acid, Computational biology and bioinformatics, Actinobacteria, Chemistry, 030104 developmental biology, Enzyme, Neuroprotective Agents, chemistry, Biochemistry, biology.protein, lcsh:Q, Cholinesterase Inhibitors, Diterpene, Diterpenes, Biotechnology
Abstract

An actinomycete strain CSR-4 was isolated from the rhizosphere soil of Zingiber montanum. Taxonomic characterization revealed strain CSR-4 was a member of the genus Microbispora. Whole-genome sequence analysis exhibited the highest average nucleotide identity (ANI) value (95.34%) and digital DNA–DNA hybridization (DDH) value (74.7%) between strain CSR-4 and the closest relative M. hainanensis DSM 45428T, which was in line with the assignment to same species. In addition, a new diterpene compound, 2α-hydroxy-8(14), 15-pimaradien-17, 18-dioic acid, and nine known compounds were isolated from the ethyl acetate crude extract of fermentation broth. Interestingly, a new diterpene displayed the suppressive effect on the recombinant human acetylcholinesterase (rhAChE) enzymes (IC50 96.87 ± 2.31 μg/ml). In silico studies based on molecular docking and molecular dynamics (MD) simulations were performed to predict a binding mode of the new compound into the binding pocket of the rhAChE enzyme and revealed that some amino acids in the peripheral anions site (PAS), anionic subsite, oxyanion site and catalytic active site (CAS) of the rhAChE have interacted with the compound. Therefore, our new compound could be proposed as a potential active human AChE inhibitor. Moreover, the new compound can protect significantly the neuron cells (% neuron viability = 88.56 ± 5.19%) from oxidative stress induced by serum deprivation method at 1 ng/ml without both neurotoxicities on murine P19-derived neuron cells and cytotoxicity against Vero cells.

Published
2020

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