Supat Jiranusornkul | Chiang Mai University (original) (raw)

Papers by Supat Jiranusornkul

Research paper thumbnail of Inhibitory effects of Indonesian temu kunci (<i>Boesenbergia rotunda</i>) rhizome extract on nitric oxide synthase production and on the kidneys of Wistar rats

World Academy of Sciences journal, Sep 20, 2022

Nitric oxide synthases (NOSs) are enzymes that function by generating nitric oxide (NO) from its ... more Nitric oxide synthases (NOSs) are enzymes that function by generating nitric oxide (NO) from its substrate, L-arginine, in human tissues. There are three known isoforms of NOS, eNOS (endothelial NOS), nNOS (neuronal NOS), and iNOS (inducible NOS). iNOS is released in response to inflammation. The human iNOS inhibitor, S-ethylisothiourea (SEITU), has been found to attach to a Glu377 residue within the active-site cavity of the enzyme. The discovery of iNOS inhibitors is always challenging. Boesenbergia rotunda (B. rotunda) has been reported to reduce inflammation in an animal model. The present study examined the inhibitory effects of B. rotunda rhizome ethanolic extract (BRE) on iNOS using the fluorometric method and investigated the histopathological effects of higher concentrations of BRE (1,000, 2,000 and 4,000 mg/kg body weight) on the kidneys of male Wistar rats. Molecular docking simulation of quercetin and kaempferol towards iNOS was also performed. The phytochemical screening of BRE indicated the presence of polyphenolics, flavonoids, triterpenoids, and saponins. The in vitro experiment confirmed that BRE reduced NO production with a half-maximal inhibitory concentration value of 79.06 µg/ml. Both quercetin and kaempferol interacted with Glu377 by building hydrogen bonds. Furthermore, the animal experiment resulted in no mortality and no marked morphological changes in the rat kidneys at all concentrations, indicating the safety of BRE as regards this organ. Taken together, BRE may be further developed as a safe anti-inflammatory drug candidate.

Research paper thumbnail of Potential use of lapatinib in the treatment of head and neck squamous cell carcinoma (Review)

World Academy of Sciences Journal

To date, cetuximab is the only anti-epidermal growth factor receptor (EGFR) monoclonal antibody (... more To date, cetuximab is the only anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) approved for the targeted therapy of head and neck squamous cell carcinoma (HNSCC). However, this therapy has left an eloquent number of patients with recurrence and local or/and distance failures, which are associated with Erb-B2 receptor tyrosine kinase 2 (ERBB2) signaling. The dual targeting (EGFR/ERBB2) irreversible covalent tyrosine kinase inhibitor (TKI), afatinib, has exhibited promising results in HNSCC trials; however, its toxicity arises from further biosynthesis for receptor recovery. Conversely, lapatinib, a reversible TKI, is almost as potent as afatinib, and its interaction with the unique inactive conformation of EGFR has been shown to be associated with its selectivity, specificity and long residence time, resulting in efficacy. However, as a monotherapy, lapatinib appears minimally active and hepatotoxicity has been reported with its use. The present review article summarizes some of the research conducted over the years in order to determine the profile of lapatinib along, with its potential for use in the treatment of HNSCC and associated challenges.

Research paper thumbnail of Lipid Profile, Antioxidant and Antihypertensive Activity, and Computational Molecular Docking of Diatom Fatty Acids as ACE Inhibitors

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Adverse events related to herbal products used by patients presenting at emergency departments

Herbal medications are gaining popularity in many countries. Although most can be used without an... more Herbal medications are gaining popularity in many countries. Although most can be used without any problem, serious toxicities do occur. Adverse events can be anticipated when herbal medications are used at excessive dose, long-term, for non-approved indications or by patients who are using multiple medications. Adverse events should be anticipated when these herbal medications with identified pharmacological effects or toxic ingredients are used. Healthcare professionals need to discuss or advise patients regarding their use. Physician-obtained medication histories towards specific herbal product use could provide relevant pharmacologic information and uncover cases of adverse events or toxicity from the used herbal products.

Research paper thumbnail of Suggested Quarantine Decision for International Travelers in COVID-19 Situation in Thailand: A Case Report

Chiang Mai University Journal of Natural Sciences, 2022

During the COVID-19 pandemic, international travelling has been altered. Thailand requires a 14-d... more During the COVID-19 pandemic, international travelling has been altered. Thailand requires a 14-day travel quarantine for travelers entering the country. However, extra self-quarantine might be ordered by the local authorities, so the healthy travelers could be kept isolated and excluded from work or other responsibilities. We reported a male traveler who was unnecessarily quarantined for 30 days since he arrived Thailand. Based on a symptom and an antibody result, we also proposed the promising quarantine decision for international travelers in Thailand. Reducing the length of quarantine may make it easier for people to quarantine by reducing the time they cannot work. A shorter quarantine period also can lessen stress on the public health system, especially when new infections are rapidly rising. Keywords: COVID-19, International travelers, Quarantine decision, Thailand

Research paper thumbnail of Estimation of Retention Time in GC/MS of Volatile Metabolites in Fragrant Rice Using Principle Components of Molecular Descriptors

Analytical Sciences, 2017

A quantitative structure-retention relationship (QSRR) study was applied for an estimation of ret... more A quantitative structure-retention relationship (QSRR) study was applied for an estimation of retention times of secondary volatile metabolites in Thai jasmine rice. In this study, chemical components in rice seed were extracted using solvent extraction, then separated and identified by gas chromatography-mass spectrometry (GC-MS). A set of molecular descriptors was generated for these substances obtained from GC-MS analysis to numerically represent the molecular structure of such compounds. Principal component analysis (PCA) and principal component regression analysis (PCR) were used to model the retention times of these compounds as a function of the theoretically derived descriptors. The best fitted regression model was obtained with R-squared of 0.900. The informative chemical properties related to retention time were elucidated. The results of this study demonstrate clearly that the combination of molecular weight and autocorrelation functions of two dimensional interatomic distance, which are molecular polarizability, atom identity, sigma charge, sigma electronegativity and polarizability, can be considered as comprehensive factors for predicting the retention times of volatile compounds in rice.

Research paper thumbnail of Pairwise Decomposition of Residue Interaction Energies Using Semiempirical Quantum Mechanical Methods in Studies of Protein−Ligand Interaction

Journal of the American Chemical Society, 2005

Pairwise decomposition of the interaction energy between molecules is shown to be a powerful tool... more Pairwise decomposition of the interaction energy between molecules is shown to be a powerful tool that can increase our understanding of macromolecular recognition processes. Herein we calculate the pairwise decomposition of the interaction energy between the protein human carbonic anhydrase II (HCAII) and the fluorine-substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) using semiempirical quantum mechanics based methods. We dissect the interaction between the ligand and the protein by dividing the ligand and the protein into subsystems to understand the structure-activity relationships as a result of fluorine substitution. In particular, the off-diagonal elements of the Fock matrix that is composed of the interaction between the ionic core and the valence electrons and the exchange energy between the subsystems or atoms of interest is examined in detail. Our analysis reveals that the fluorine-substituted benzylamine group of SBB does not directly affect the binding energy. Rather, we find that the strength of the interaction between Thr199 of HCAII and the sulfamylbenzoyl group of SBB affects the binding affinity between the protein and the ligand. These observations underline the importance of the sulfonamide group in binding affinity as shown by previous experiments (Maren, T. H.; Wiley: C. E. J. Med. Chem. 1968, 11, 228-232). Moreover, our calculations qualitatively agree with the structural aspects of these protein-ligand complexes as determined by X-ray crystallography.

Research paper thumbnail of The Binding of Alpinia galanga Oil and Its Nanoemulsion to Mammal GABAA Receptors Using Rat Cortical Membranes and an In Silico Modeling Platform

Pharmaceutics, 2022

The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its p... more The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its pathway in mammals is limited. In the present study, the binding of AGO and its key compounds, methyl eugenol, 1,8-cineole, and 4-allylphenyl acetate, to gamma-aminobutyric acid type A (GABAA) receptors in rat cortical membranes, was investigated using a [3H]muscimol binding assay and an in silico modeling platform. The results showed that only AGO and methyl eugenol displayed a positive modulation at the highest concentrations, whereas 1,8-cineole and 4-allylphenyl acetate were inactive. The result of AGO correlated well to the amount of methyl eugenol in AGO. Computational docking and dynamics simulations into the GABAA receptor complex model (PDB: 6X3T) showed the stable structure of the GABAA receptor–methyl eugenol complex with the lowest binding energy of −22.16 kcal/mol. This result shows that the anesthetic activity of AGO and methyl eugenol in mammals is associated with GABAA rec...

Research paper thumbnail of Molecular modelling studies of DNA damage recognition

How DNA repair proteins search and recognise the rare sites of damage from the massive numbers of... more How DNA repair proteins search and recognise the rare sites of damage from the massive numbers of normal DNA remains poorly understood. FapydG (2,6-diamino-4-hydroxy-5-formamidopyrimidine) is one of the most prevalent guanine derived lesions involving opening of the imidazole ring. It is typically repaired by formamidopyrimidine-DNA glycosylase (Fpg) as an initial step in base excision repair; if not repaired, the lesion generates a G: C -+ T: A transversion. Unfortunately, studies on the recognition of FapydG have been hindered by difficulties to synthesise and incorporate the FapydG residue into a DNA duplex. Crystal structures of Fpg-DNA complexes have demonstrated three common recognition events: the protein specifically binding to the extrahelical lesion, bending DNA centred on the damaged base, and flipping the damage into the pocket. Thus, molecular modelling and dynamics simulation have been used to gather dynamical information of those recognition events for damaged and und...

Research paper thumbnail of Potential Anti-Alzheimer Agents from Guanidinyl Tryptophan Derivatives with Activities of Membrane Adhesion and Conformational Transition Inhibitions

Molecules, 2021

Guanidinyl tryptophan derivatives TGN1, TGN2, TGN3, and TGN4 were synthesized, and these compound... more Guanidinyl tryptophan derivatives TGN1, TGN2, TGN3, and TGN4 were synthesized, and these compounds were shown to possess in vitro inhibitory activity for amyloid aggregation in a previous study. Nevertheless, the influence of the TGN series of compounds on the binding and permeation behaviors of an Aβ monomer to the cell membranes was not elucidated. In this study, we investigated the effect of compounds in the TGN series on the behavior of an Aβ monomer regarding its toxicity toward the bilayer lipid membrane using molecular dynamics (MD) simulation. MD simulations suggest that TGN4 is a potential agent that can interfere with the movement of the Aβ monomer into the membrane. The MM-GBSA result demonstrated that TGN4 exhibits the highest affinity to the Aβ1–42 monomer but has the lowest affinity to the bilayer. Moreover, TGN4 also contributes to a decrease in the binding affinity between the Aβ1–42 monomer and the POPC membrane. Regarding the results of the binding mode and conform...

Research paper thumbnail of Effect of molecular weight of poly(ethylene glycol) as humectant in interpenetrating polymer network hydrogels based on poly(sodium AMPS) and gelatin for wound dressing applications

International Journal of Polymeric Materials and Polymeric Biomaterials

Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin con... more Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin containing different molecular weights of poly(ethylene glycol) (PEG) as a humectant were prepared via UV photopolymerization. The results indicated that the PEG slowed down evaporative water loss and water vapor transmission. Water transport, whether it was absorption, transmission or evaporation, and also tensile properties were found to be dependent to varying extents on the PEG molecular weight. These results could also be related to the amount of non-freezable water, as determined by differential scanning calorimetry. These properties and their relevance to the hydrogel’s potential use as a wound dressing are discussed. Graphical Abstract

Research paper thumbnail of Effects on Steroid 5-Alpha Reductase Gene Expression of Thai Rice Bran Extracts and Molecular Dynamics Study on SRD5A2

Biology

Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydro... more Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydrotestosterone, a potent androgen, which is the aetiologic factor of androgenetic alopecia. This study aimed to compare the SRD5A gene expression suppression activity exerted by Thai rice bran extracts and their components and investigate the interactional mechanism between bioactive compounds and SRD5A2 using molecular dynamics (MD) simulation. Bran of Oryza sativa cv. Tubtim Chumphae (TRB), Yamuechaebia Morchor (YRB), Riceberry (RRB), and Malinil Surin (MRB), all rice milling by-products, was solvent-extracted. The ethanolic extract of TRB had the highest sum of overall bioactive compounds (γ-oryzanol; α-, β-, and γ-tocopherol; phenolics; and flavonoids). Among all extracts, TRB greatly downregulated the expression of SRD5A1, SRD5A2, and SRD5A3; there were no significant differences between TRB and finasteride regarding SRD5A suppression. The linear relationship and principal component a...

Research paper thumbnail of Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules

Molecular and Cellular Biochemistry

Synaptotagmin 1 (Syt1) is the Ca2+ sensor protein with an essential role in neurotransmitter rele... more Synaptotagmin 1 (Syt1) is the Ca2+ sensor protein with an essential role in neurotransmitter release. Since the wrinkle formation is due to the excessive muscle fiber stimulation in the face, a helpful stratagem to diminish the wrinkle line intenseness is to weaken the innervating neuron activity through Syt1 inhibition which is one of the possible therapeutic strategies against wrinkles. Recently, experimental evidence showed that botox-like peptides, which are typically used as SNARE modulators, may inhibit Syt1. In this work, we applied molecular modeling to (1) characterize the structural framework and (2) define the atomistic information of the factors for the inhibition mechanism. The modeling identified the plausible binding cleft able to efficiently bind all botox-like peptides. The MD simulations revealed that all peptides induced significant Syt1 rigidity by binding in the cleft of the C2A–C2B interface. The consequence of this binding event is the suppression of the protein motion associated with conformational change of Syt1 from the closed form to the open form. On this basis, this finding may therefore be of subservience for the advancement of novel botox-like molecules for the therapeutic treatment of wrinkle, targeting and modulating the function of Syt1.

Research paper thumbnail of Characteristic Structural Knowledge for Morphological Identification and Classification in Meso-Scale Simulations Using Principal Component Analysis

Polymers

Meso-scale simulations have been widely used to probe aggregation caused by structural formation ... more Meso-scale simulations have been widely used to probe aggregation caused by structural formation in macromolecular systems. However, the limitations of the long-length scale, resulting from its simulation box, cause difficulties in terms of morphological identification and insufficient classification. In this study, structural knowledge derived from meso-scale simulations based on parameters from atomistic simulations were analyzed in dissipative particle dynamic (DPD) simulations of PS-b-PI diblock copolymers. The radial distribution function and its Fourier-space counterpart or structure factor were proposed using principal component analysis (PCA) as key characteristics for morphological identification and classification. Disorder, discrete clusters, hexagonally packed cylinders, connected clusters, defected lamellae, lamellae and connected cylinders were effectively grouped.

Research paper thumbnail of Molecular modeling for potential cathepsin L inhibitor identification as new anti-photoaging agents from tropical medicinal plants

Journal of Bioenergetics and Biomembranes

Ultraviolet exposure can cause photoaging toward the human skin which is begun by the inflammatio... more Ultraviolet exposure can cause photoaging toward the human skin which is begun by the inflammation on the exposure area, also resulting in activation of a degradative enzyme cathepsin L. This enzyme is one of the interesting novel therapeutic targets for antiaging agents. Three plants, named Kleinhovia hospita, Aleurites moluccana, and Centella asiatica, are well-known in the tropical region as anti-inflammatory herbs. The aims of this study were to predict the antiaging activity of the 31 compounds from these plants via inhibition of cathepsin L. All compounds were minimized their energies and then used in molecular docking. After that, molecular dynamics (MD) simulation was employed for the 5 candidate ligands and the positive control; schinol. Interaction analysis results of the pre-MD and post-MD simulation structures were obtained. Furthermore, a toxicity test was performed using ADMET Predictor 7.1. Based on the molecular docking and the MD simulation results, kleinhospitine A, β-amyrin, and castiliferol exhibited lower binding free energy than schinol (−27.0925, −28.6813, −26.0037 kcal/mol) and also had interactions with the S´ region binding site. The toxicity test indicated that β-amyrin is the most potential candidate since it exhibited the lowest binding energy and the high safety level.

Research paper thumbnail of Molecular Modeling for a Comparative Analysis of Interactions Between 2LTRZFP and 2-LTR-Circle Junctions

International Journal of Peptide Research and Therapeutics

In eukaryotes, one of the most often noticed DNA-binding motifs are Cys2His2 zinc finger proteins... more In eukaryotes, one of the most often noticed DNA-binding motifs are Cys2His2 zinc finger proteins which have been extensively utilized as a framework for designing novel DNA-binding proteins. In this study, the conformational change, and binding stability, affinity and interactions of the 2LTRZFP–HIV-1 2-LTR-circle junction complexes were successfully reproduced with MD simulations, MM-PBSA/GBSA and binding mode analyses. The binding free energies were obtained, and it was found that the calculated binding free energy of Zif1 is lower than Zif2 and together with pharmacophore modeling, these binding results indicate strong affinity of 2LTRZFP for the DNA. Mutants of 2LTRZFP were analyzed. The computed energies provided proof for a relationship between the binding free energy and total electrostatic interaction energy. The mutation in a key amino acid (Glu81Tyr) of the finger 3 in position 6 showed increased binding energy to the DNA. The result agrees with our previous study which showed that the HIV-1 IN may be hindered by the 2LTRZFP. The obtained results may assist in the design of ZFPs depended on the 2-LTR-circle junctions inhibition mechanism.

Research paper thumbnail of Novel Multifunctional Ascorbic Triazole Derivatives for Amyloidogenic Pathway Inhibition, Anti-Inflammation, and Neuroprotection

Molecules

Alzheimer’s disease (AD) is a common neurodegenerative disorder. The number of patients with AD i... more Alzheimer’s disease (AD) is a common neurodegenerative disorder. The number of patients with AD is projected to reach 152 million by 2050. Donepezil, rivastigmine, galantamine, and memantine are the only four drugs currently approved by the United States Food and Drug Administration for AD treatment. However, these drugs can only alleviate AD symptoms. Thus, this research focuses on the discovery of novel lead compounds that possess multitarget regulation of AD etiopathology relating to amyloid cascade. The ascorbic acid structure has been designated as a core functional domain due to several characteristics, including antioxidant activities, amyloid aggregation inhibition, and the ability to be transported to the brain and neurons. Multifunctional ascorbic derivatives were synthesized by copper (I)-catalyzed azide–alkyne cycloaddition reaction (click chemistry). The in vitro and cell-based assays showed that compounds 2c and 5c exhibited prominent multifunctional activities as beta...

Research paper thumbnail of Tentative Peptide‒Lipid Bilayer Models Elucidating Molecular Behaviors and Interactions Driving Passive Cellular Uptake of Collagen-Derived Small Peptides

Molecules

Collagen contains hydroxyproline (Hyp), which is a unique amino acid. Three collagen-derived smal... more Collagen contains hydroxyproline (Hyp), which is a unique amino acid. Three collagen-derived small peptides (Gly-Pro-Hyp, Pro-Hyp, and Gly-Hyp) interacting across a lipid bilayer (POPC model membrane) for cellular uptakes of these collagen-derived small peptides were studied using accelerated molecular dynamics simulation. The ligands were investigated for their binding modes, hydrogen bonds in each coordinate frame, and mean square displacement (MSD) in the Z direction. The lipid bilayers were evaluated for mass and electron density profiles of the lipid molecules, surface area of the head groups, and root mean square deviation (RMSD). The simulation results show that hydrogen bonding between the small collagen peptides and plasma membrane plays a significant role in their internalization. The translocation of the small collagen peptides across the cell membranes was shown. Pro-Hyp laterally condensed the membrane, resulting in an increase in the bilayer thickness and rigidity. Per...

Research paper thumbnail of Depletion of β-sitosterol and enrichment of quercetin and rutin in Cissus quadrangularis Linn fraction enhanced osteogenic but reduced osteoclastogenic marker expression

BMC Complementary Medicine and Therapies

Background Cissus quadrangularis Linn. (CQ) has been used in Indian and Thai traditional medicine... more Background Cissus quadrangularis Linn. (CQ) has been used in Indian and Thai traditional medicine for healing bone fractures because of numerous active ingredients in CQ. It is still unclear which compounds are the active ingredients for bone formation. Methods The molecular docking technique, the ethanolic extraction along with hexane fractionation, and an in vitro experiment with a human osteoblast cell line (MG-63) were used to narrow down the active compounds, to prepare the CQ extract, and to test biological activities, respectively. Results The molecular docking technique revealed that quercetin and β-sitosterol had highest and lowest potential to bind to estrogen receptors, respectively. Compared to the crude ethanol extract (P1), the ethanolic fraction (P2) was enriched with rutin and quercetin at 65.36 ± 0.75 and 1.06 ± 0.12 mg/g, respectively. Alkaline phosphatase (ALP) activity was significantly enhanced in osteoblasts exposed to the P2 in both tested concentrations. The ...

Research paper thumbnail of Effect of molecular weight of poly(ethylene glycol) as humectant in interpenetrating polymer network hydrogels based on poly(sodium AMPS) and gelatin for wound dressing applications

International Journal of Polymeric Materials and Polymeric Biomaterials

Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin con... more Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin containing different molecular weights of poly(ethylene glycol) (PEG) as a humectant were prepared via UV photopolymerization. The results indicated that the PEG slowed down evaporative water loss and water vapor transmission. Water transport, whether it was absorption, transmission or evaporation, and also tensile properties were found to be dependent to varying extents on the PEG molecular weight. These results could also be related to the amount of non-freezable water, as determined by differential scanning calorimetry. These properties and their relevance to the hydrogel’s potential use as a wound dressing are discussed. Graphical Abstract

Research paper thumbnail of Inhibitory effects of Indonesian temu kunci (<i>Boesenbergia rotunda</i>) rhizome extract on nitric oxide synthase production and on the kidneys of Wistar rats

World Academy of Sciences journal, Sep 20, 2022

Nitric oxide synthases (NOSs) are enzymes that function by generating nitric oxide (NO) from its ... more Nitric oxide synthases (NOSs) are enzymes that function by generating nitric oxide (NO) from its substrate, L-arginine, in human tissues. There are three known isoforms of NOS, eNOS (endothelial NOS), nNOS (neuronal NOS), and iNOS (inducible NOS). iNOS is released in response to inflammation. The human iNOS inhibitor, S-ethylisothiourea (SEITU), has been found to attach to a Glu377 residue within the active-site cavity of the enzyme. The discovery of iNOS inhibitors is always challenging. Boesenbergia rotunda (B. rotunda) has been reported to reduce inflammation in an animal model. The present study examined the inhibitory effects of B. rotunda rhizome ethanolic extract (BRE) on iNOS using the fluorometric method and investigated the histopathological effects of higher concentrations of BRE (1,000, 2,000 and 4,000 mg/kg body weight) on the kidneys of male Wistar rats. Molecular docking simulation of quercetin and kaempferol towards iNOS was also performed. The phytochemical screening of BRE indicated the presence of polyphenolics, flavonoids, triterpenoids, and saponins. The in vitro experiment confirmed that BRE reduced NO production with a half-maximal inhibitory concentration value of 79.06 µg/ml. Both quercetin and kaempferol interacted with Glu377 by building hydrogen bonds. Furthermore, the animal experiment resulted in no mortality and no marked morphological changes in the rat kidneys at all concentrations, indicating the safety of BRE as regards this organ. Taken together, BRE may be further developed as a safe anti-inflammatory drug candidate.

Research paper thumbnail of Potential use of lapatinib in the treatment of head and neck squamous cell carcinoma (Review)

World Academy of Sciences Journal

To date, cetuximab is the only anti-epidermal growth factor receptor (EGFR) monoclonal antibody (... more To date, cetuximab is the only anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) approved for the targeted therapy of head and neck squamous cell carcinoma (HNSCC). However, this therapy has left an eloquent number of patients with recurrence and local or/and distance failures, which are associated with Erb-B2 receptor tyrosine kinase 2 (ERBB2) signaling. The dual targeting (EGFR/ERBB2) irreversible covalent tyrosine kinase inhibitor (TKI), afatinib, has exhibited promising results in HNSCC trials; however, its toxicity arises from further biosynthesis for receptor recovery. Conversely, lapatinib, a reversible TKI, is almost as potent as afatinib, and its interaction with the unique inactive conformation of EGFR has been shown to be associated with its selectivity, specificity and long residence time, resulting in efficacy. However, as a monotherapy, lapatinib appears minimally active and hepatotoxicity has been reported with its use. The present review article summarizes some of the research conducted over the years in order to determine the profile of lapatinib along, with its potential for use in the treatment of HNSCC and associated challenges.

Research paper thumbnail of Lipid Profile, Antioxidant and Antihypertensive Activity, and Computational Molecular Docking of Diatom Fatty Acids as ACE Inhibitors

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Adverse events related to herbal products used by patients presenting at emergency departments

Herbal medications are gaining popularity in many countries. Although most can be used without an... more Herbal medications are gaining popularity in many countries. Although most can be used without any problem, serious toxicities do occur. Adverse events can be anticipated when herbal medications are used at excessive dose, long-term, for non-approved indications or by patients who are using multiple medications. Adverse events should be anticipated when these herbal medications with identified pharmacological effects or toxic ingredients are used. Healthcare professionals need to discuss or advise patients regarding their use. Physician-obtained medication histories towards specific herbal product use could provide relevant pharmacologic information and uncover cases of adverse events or toxicity from the used herbal products.

Research paper thumbnail of Suggested Quarantine Decision for International Travelers in COVID-19 Situation in Thailand: A Case Report

Chiang Mai University Journal of Natural Sciences, 2022

During the COVID-19 pandemic, international travelling has been altered. Thailand requires a 14-d... more During the COVID-19 pandemic, international travelling has been altered. Thailand requires a 14-day travel quarantine for travelers entering the country. However, extra self-quarantine might be ordered by the local authorities, so the healthy travelers could be kept isolated and excluded from work or other responsibilities. We reported a male traveler who was unnecessarily quarantined for 30 days since he arrived Thailand. Based on a symptom and an antibody result, we also proposed the promising quarantine decision for international travelers in Thailand. Reducing the length of quarantine may make it easier for people to quarantine by reducing the time they cannot work. A shorter quarantine period also can lessen stress on the public health system, especially when new infections are rapidly rising. Keywords: COVID-19, International travelers, Quarantine decision, Thailand

Research paper thumbnail of Estimation of Retention Time in GC/MS of Volatile Metabolites in Fragrant Rice Using Principle Components of Molecular Descriptors

Analytical Sciences, 2017

A quantitative structure-retention relationship (QSRR) study was applied for an estimation of ret... more A quantitative structure-retention relationship (QSRR) study was applied for an estimation of retention times of secondary volatile metabolites in Thai jasmine rice. In this study, chemical components in rice seed were extracted using solvent extraction, then separated and identified by gas chromatography-mass spectrometry (GC-MS). A set of molecular descriptors was generated for these substances obtained from GC-MS analysis to numerically represent the molecular structure of such compounds. Principal component analysis (PCA) and principal component regression analysis (PCR) were used to model the retention times of these compounds as a function of the theoretically derived descriptors. The best fitted regression model was obtained with R-squared of 0.900. The informative chemical properties related to retention time were elucidated. The results of this study demonstrate clearly that the combination of molecular weight and autocorrelation functions of two dimensional interatomic distance, which are molecular polarizability, atom identity, sigma charge, sigma electronegativity and polarizability, can be considered as comprehensive factors for predicting the retention times of volatile compounds in rice.

Research paper thumbnail of Pairwise Decomposition of Residue Interaction Energies Using Semiempirical Quantum Mechanical Methods in Studies of Protein−Ligand Interaction

Journal of the American Chemical Society, 2005

Pairwise decomposition of the interaction energy between molecules is shown to be a powerful tool... more Pairwise decomposition of the interaction energy between molecules is shown to be a powerful tool that can increase our understanding of macromolecular recognition processes. Herein we calculate the pairwise decomposition of the interaction energy between the protein human carbonic anhydrase II (HCAII) and the fluorine-substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) using semiempirical quantum mechanics based methods. We dissect the interaction between the ligand and the protein by dividing the ligand and the protein into subsystems to understand the structure-activity relationships as a result of fluorine substitution. In particular, the off-diagonal elements of the Fock matrix that is composed of the interaction between the ionic core and the valence electrons and the exchange energy between the subsystems or atoms of interest is examined in detail. Our analysis reveals that the fluorine-substituted benzylamine group of SBB does not directly affect the binding energy. Rather, we find that the strength of the interaction between Thr199 of HCAII and the sulfamylbenzoyl group of SBB affects the binding affinity between the protein and the ligand. These observations underline the importance of the sulfonamide group in binding affinity as shown by previous experiments (Maren, T. H.; Wiley: C. E. J. Med. Chem. 1968, 11, 228-232). Moreover, our calculations qualitatively agree with the structural aspects of these protein-ligand complexes as determined by X-ray crystallography.

Research paper thumbnail of The Binding of Alpinia galanga Oil and Its Nanoemulsion to Mammal GABAA Receptors Using Rat Cortical Membranes and an In Silico Modeling Platform

Pharmaceutics, 2022

The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its p... more The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its pathway in mammals is limited. In the present study, the binding of AGO and its key compounds, methyl eugenol, 1,8-cineole, and 4-allylphenyl acetate, to gamma-aminobutyric acid type A (GABAA) receptors in rat cortical membranes, was investigated using a [3H]muscimol binding assay and an in silico modeling platform. The results showed that only AGO and methyl eugenol displayed a positive modulation at the highest concentrations, whereas 1,8-cineole and 4-allylphenyl acetate were inactive. The result of AGO correlated well to the amount of methyl eugenol in AGO. Computational docking and dynamics simulations into the GABAA receptor complex model (PDB: 6X3T) showed the stable structure of the GABAA receptor–methyl eugenol complex with the lowest binding energy of −22.16 kcal/mol. This result shows that the anesthetic activity of AGO and methyl eugenol in mammals is associated with GABAA rec...

Research paper thumbnail of Molecular modelling studies of DNA damage recognition

How DNA repair proteins search and recognise the rare sites of damage from the massive numbers of... more How DNA repair proteins search and recognise the rare sites of damage from the massive numbers of normal DNA remains poorly understood. FapydG (2,6-diamino-4-hydroxy-5-formamidopyrimidine) is one of the most prevalent guanine derived lesions involving opening of the imidazole ring. It is typically repaired by formamidopyrimidine-DNA glycosylase (Fpg) as an initial step in base excision repair; if not repaired, the lesion generates a G: C -+ T: A transversion. Unfortunately, studies on the recognition of FapydG have been hindered by difficulties to synthesise and incorporate the FapydG residue into a DNA duplex. Crystal structures of Fpg-DNA complexes have demonstrated three common recognition events: the protein specifically binding to the extrahelical lesion, bending DNA centred on the damaged base, and flipping the damage into the pocket. Thus, molecular modelling and dynamics simulation have been used to gather dynamical information of those recognition events for damaged and und...

Research paper thumbnail of Potential Anti-Alzheimer Agents from Guanidinyl Tryptophan Derivatives with Activities of Membrane Adhesion and Conformational Transition Inhibitions

Molecules, 2021

Guanidinyl tryptophan derivatives TGN1, TGN2, TGN3, and TGN4 were synthesized, and these compound... more Guanidinyl tryptophan derivatives TGN1, TGN2, TGN3, and TGN4 were synthesized, and these compounds were shown to possess in vitro inhibitory activity for amyloid aggregation in a previous study. Nevertheless, the influence of the TGN series of compounds on the binding and permeation behaviors of an Aβ monomer to the cell membranes was not elucidated. In this study, we investigated the effect of compounds in the TGN series on the behavior of an Aβ monomer regarding its toxicity toward the bilayer lipid membrane using molecular dynamics (MD) simulation. MD simulations suggest that TGN4 is a potential agent that can interfere with the movement of the Aβ monomer into the membrane. The MM-GBSA result demonstrated that TGN4 exhibits the highest affinity to the Aβ1–42 monomer but has the lowest affinity to the bilayer. Moreover, TGN4 also contributes to a decrease in the binding affinity between the Aβ1–42 monomer and the POPC membrane. Regarding the results of the binding mode and conform...

Research paper thumbnail of Effect of molecular weight of poly(ethylene glycol) as humectant in interpenetrating polymer network hydrogels based on poly(sodium AMPS) and gelatin for wound dressing applications

International Journal of Polymeric Materials and Polymeric Biomaterials

Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin con... more Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin containing different molecular weights of poly(ethylene glycol) (PEG) as a humectant were prepared via UV photopolymerization. The results indicated that the PEG slowed down evaporative water loss and water vapor transmission. Water transport, whether it was absorption, transmission or evaporation, and also tensile properties were found to be dependent to varying extents on the PEG molecular weight. These results could also be related to the amount of non-freezable water, as determined by differential scanning calorimetry. These properties and their relevance to the hydrogel’s potential use as a wound dressing are discussed. Graphical Abstract

Research paper thumbnail of Effects on Steroid 5-Alpha Reductase Gene Expression of Thai Rice Bran Extracts and Molecular Dynamics Study on SRD5A2

Biology

Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydro... more Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydrotestosterone, a potent androgen, which is the aetiologic factor of androgenetic alopecia. This study aimed to compare the SRD5A gene expression suppression activity exerted by Thai rice bran extracts and their components and investigate the interactional mechanism between bioactive compounds and SRD5A2 using molecular dynamics (MD) simulation. Bran of Oryza sativa cv. Tubtim Chumphae (TRB), Yamuechaebia Morchor (YRB), Riceberry (RRB), and Malinil Surin (MRB), all rice milling by-products, was solvent-extracted. The ethanolic extract of TRB had the highest sum of overall bioactive compounds (γ-oryzanol; α-, β-, and γ-tocopherol; phenolics; and flavonoids). Among all extracts, TRB greatly downregulated the expression of SRD5A1, SRD5A2, and SRD5A3; there were no significant differences between TRB and finasteride regarding SRD5A suppression. The linear relationship and principal component a...

Research paper thumbnail of Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules

Molecular and Cellular Biochemistry

Synaptotagmin 1 (Syt1) is the Ca2+ sensor protein with an essential role in neurotransmitter rele... more Synaptotagmin 1 (Syt1) is the Ca2+ sensor protein with an essential role in neurotransmitter release. Since the wrinkle formation is due to the excessive muscle fiber stimulation in the face, a helpful stratagem to diminish the wrinkle line intenseness is to weaken the innervating neuron activity through Syt1 inhibition which is one of the possible therapeutic strategies against wrinkles. Recently, experimental evidence showed that botox-like peptides, which are typically used as SNARE modulators, may inhibit Syt1. In this work, we applied molecular modeling to (1) characterize the structural framework and (2) define the atomistic information of the factors for the inhibition mechanism. The modeling identified the plausible binding cleft able to efficiently bind all botox-like peptides. The MD simulations revealed that all peptides induced significant Syt1 rigidity by binding in the cleft of the C2A–C2B interface. The consequence of this binding event is the suppression of the protein motion associated with conformational change of Syt1 from the closed form to the open form. On this basis, this finding may therefore be of subservience for the advancement of novel botox-like molecules for the therapeutic treatment of wrinkle, targeting and modulating the function of Syt1.

Research paper thumbnail of Characteristic Structural Knowledge for Morphological Identification and Classification in Meso-Scale Simulations Using Principal Component Analysis

Polymers

Meso-scale simulations have been widely used to probe aggregation caused by structural formation ... more Meso-scale simulations have been widely used to probe aggregation caused by structural formation in macromolecular systems. However, the limitations of the long-length scale, resulting from its simulation box, cause difficulties in terms of morphological identification and insufficient classification. In this study, structural knowledge derived from meso-scale simulations based on parameters from atomistic simulations were analyzed in dissipative particle dynamic (DPD) simulations of PS-b-PI diblock copolymers. The radial distribution function and its Fourier-space counterpart or structure factor were proposed using principal component analysis (PCA) as key characteristics for morphological identification and classification. Disorder, discrete clusters, hexagonally packed cylinders, connected clusters, defected lamellae, lamellae and connected cylinders were effectively grouped.

Research paper thumbnail of Molecular modeling for potential cathepsin L inhibitor identification as new anti-photoaging agents from tropical medicinal plants

Journal of Bioenergetics and Biomembranes

Ultraviolet exposure can cause photoaging toward the human skin which is begun by the inflammatio... more Ultraviolet exposure can cause photoaging toward the human skin which is begun by the inflammation on the exposure area, also resulting in activation of a degradative enzyme cathepsin L. This enzyme is one of the interesting novel therapeutic targets for antiaging agents. Three plants, named Kleinhovia hospita, Aleurites moluccana, and Centella asiatica, are well-known in the tropical region as anti-inflammatory herbs. The aims of this study were to predict the antiaging activity of the 31 compounds from these plants via inhibition of cathepsin L. All compounds were minimized their energies and then used in molecular docking. After that, molecular dynamics (MD) simulation was employed for the 5 candidate ligands and the positive control; schinol. Interaction analysis results of the pre-MD and post-MD simulation structures were obtained. Furthermore, a toxicity test was performed using ADMET Predictor 7.1. Based on the molecular docking and the MD simulation results, kleinhospitine A, β-amyrin, and castiliferol exhibited lower binding free energy than schinol (−27.0925, −28.6813, −26.0037 kcal/mol) and also had interactions with the S´ region binding site. The toxicity test indicated that β-amyrin is the most potential candidate since it exhibited the lowest binding energy and the high safety level.

Research paper thumbnail of Molecular Modeling for a Comparative Analysis of Interactions Between 2LTRZFP and 2-LTR-Circle Junctions

International Journal of Peptide Research and Therapeutics

In eukaryotes, one of the most often noticed DNA-binding motifs are Cys2His2 zinc finger proteins... more In eukaryotes, one of the most often noticed DNA-binding motifs are Cys2His2 zinc finger proteins which have been extensively utilized as a framework for designing novel DNA-binding proteins. In this study, the conformational change, and binding stability, affinity and interactions of the 2LTRZFP–HIV-1 2-LTR-circle junction complexes were successfully reproduced with MD simulations, MM-PBSA/GBSA and binding mode analyses. The binding free energies were obtained, and it was found that the calculated binding free energy of Zif1 is lower than Zif2 and together with pharmacophore modeling, these binding results indicate strong affinity of 2LTRZFP for the DNA. Mutants of 2LTRZFP were analyzed. The computed energies provided proof for a relationship between the binding free energy and total electrostatic interaction energy. The mutation in a key amino acid (Glu81Tyr) of the finger 3 in position 6 showed increased binding energy to the DNA. The result agrees with our previous study which showed that the HIV-1 IN may be hindered by the 2LTRZFP. The obtained results may assist in the design of ZFPs depended on the 2-LTR-circle junctions inhibition mechanism.

Research paper thumbnail of Novel Multifunctional Ascorbic Triazole Derivatives for Amyloidogenic Pathway Inhibition, Anti-Inflammation, and Neuroprotection

Molecules

Alzheimer’s disease (AD) is a common neurodegenerative disorder. The number of patients with AD i... more Alzheimer’s disease (AD) is a common neurodegenerative disorder. The number of patients with AD is projected to reach 152 million by 2050. Donepezil, rivastigmine, galantamine, and memantine are the only four drugs currently approved by the United States Food and Drug Administration for AD treatment. However, these drugs can only alleviate AD symptoms. Thus, this research focuses on the discovery of novel lead compounds that possess multitarget regulation of AD etiopathology relating to amyloid cascade. The ascorbic acid structure has been designated as a core functional domain due to several characteristics, including antioxidant activities, amyloid aggregation inhibition, and the ability to be transported to the brain and neurons. Multifunctional ascorbic derivatives were synthesized by copper (I)-catalyzed azide–alkyne cycloaddition reaction (click chemistry). The in vitro and cell-based assays showed that compounds 2c and 5c exhibited prominent multifunctional activities as beta...

Research paper thumbnail of Tentative Peptide‒Lipid Bilayer Models Elucidating Molecular Behaviors and Interactions Driving Passive Cellular Uptake of Collagen-Derived Small Peptides

Molecules

Collagen contains hydroxyproline (Hyp), which is a unique amino acid. Three collagen-derived smal... more Collagen contains hydroxyproline (Hyp), which is a unique amino acid. Three collagen-derived small peptides (Gly-Pro-Hyp, Pro-Hyp, and Gly-Hyp) interacting across a lipid bilayer (POPC model membrane) for cellular uptakes of these collagen-derived small peptides were studied using accelerated molecular dynamics simulation. The ligands were investigated for their binding modes, hydrogen bonds in each coordinate frame, and mean square displacement (MSD) in the Z direction. The lipid bilayers were evaluated for mass and electron density profiles of the lipid molecules, surface area of the head groups, and root mean square deviation (RMSD). The simulation results show that hydrogen bonding between the small collagen peptides and plasma membrane plays a significant role in their internalization. The translocation of the small collagen peptides across the cell membranes was shown. Pro-Hyp laterally condensed the membrane, resulting in an increase in the bilayer thickness and rigidity. Per...

Research paper thumbnail of Depletion of β-sitosterol and enrichment of quercetin and rutin in Cissus quadrangularis Linn fraction enhanced osteogenic but reduced osteoclastogenic marker expression

BMC Complementary Medicine and Therapies

Background Cissus quadrangularis Linn. (CQ) has been used in Indian and Thai traditional medicine... more Background Cissus quadrangularis Linn. (CQ) has been used in Indian and Thai traditional medicine for healing bone fractures because of numerous active ingredients in CQ. It is still unclear which compounds are the active ingredients for bone formation. Methods The molecular docking technique, the ethanolic extraction along with hexane fractionation, and an in vitro experiment with a human osteoblast cell line (MG-63) were used to narrow down the active compounds, to prepare the CQ extract, and to test biological activities, respectively. Results The molecular docking technique revealed that quercetin and β-sitosterol had highest and lowest potential to bind to estrogen receptors, respectively. Compared to the crude ethanol extract (P1), the ethanolic fraction (P2) was enriched with rutin and quercetin at 65.36 ± 0.75 and 1.06 ± 0.12 mg/g, respectively. Alkaline phosphatase (ALP) activity was significantly enhanced in osteoblasts exposed to the P2 in both tested concentrations. The ...

Research paper thumbnail of Effect of molecular weight of poly(ethylene glycol) as humectant in interpenetrating polymer network hydrogels based on poly(sodium AMPS) and gelatin for wound dressing applications

International Journal of Polymeric Materials and Polymeric Biomaterials

Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin con... more Abstract Hydrogel composed of poly(sodium 2-acrylamido-2-methylpropane sulfonate) and gelatin containing different molecular weights of poly(ethylene glycol) (PEG) as a humectant were prepared via UV photopolymerization. The results indicated that the PEG slowed down evaporative water loss and water vapor transmission. Water transport, whether it was absorption, transmission or evaporation, and also tensile properties were found to be dependent to varying extents on the PEG molecular weight. These results could also be related to the amount of non-freezable water, as determined by differential scanning calorimetry. These properties and their relevance to the hydrogel’s potential use as a wound dressing are discussed. Graphical Abstract