11 pages, 4752 KiB  
Article
Pectin from Citrus Canning Wastewater as Potential Fat Replacer in Ice Cream
by Hua Zhang, Jianle Chen, Junhui Li, Chaoyang Wei, Xingqian Ye, John Shi and Shiguo Chen
Molecules 2018, 23(4), 925; https://doi.org/10.3390/molecules23040925 - 17 Apr 2018
Cited by 46 | Viewed by 7015
Abstract
Pectin had been recovered from canning wastewater produced by chemical treatment of segment membrane during preparation of canned citrus in our previous research. The purpose of this study was to characterize the extracted pectin from canning wastewater, and to evaluate its application as [...] Read more.
Pectin had been recovered from canning wastewater produced by chemical treatment of segment membrane during preparation of canned citrus in our previous research. The purpose of this study was to characterize the extracted pectin from canning wastewater, and to evaluate its application as a fat alternative to replace fat in ice cream. The monosaccharide composition and rheological properties of the pectin were determined. The influences of fat reduction and pectin addition on the physicochemical, rheological and sensory properties of low-fat ice cream were determined. The rheological results showed that pectin solutions were typical pseudoplastic fluids. The addition of pectin in ice cream can cause an increase in viscosity, overrun, and hardness, and a decrease in meltdown of the ice cream. When 0.72% pectin (w/w) is incorporated into ice cream, a prototype product of ice cream with 45% lower fat content compared to the control was made. Results indicated that their qualities such as appearance, flavor, and taste were not significantly different. The low-fat ice cream had higher smoothness scores and lower mouth-coating scores. Hence, pectin extracted from citrus canning wastewater can be potentially used as fat replacer in ice cream, which benefits both the environment and the food industry. Full article
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17 pages, 47356 KiB  
Article
Immunohistochemical Evidence from APP-Transgenic Mice for Glutaminyl Cyclase as Drug Target to Diminish pE-Abeta Formation
by Maike Hartlage-Rübsamen, Alexandra Bluhm, Anke Piechotta, Miriam Linnert, Jens-Ulrich Rahfeld, Hans-Ulrich Demuth, Inge Lues, Peer-Hendrik Kuhn, Stefan F. Lichtenthaler, Steffen Roßner and Corinna Höfling
Molecules 2018, 23(4), 924; https://doi.org/10.3390/molecules23040924 - 17 Apr 2018
Cited by 14 | Viewed by 6532
Abstract
Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer’s disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell [...] Read more.
Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer’s disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell biological properties has been demonstrated. Among these, a particularly neurotoxic and disease-specific Abeta variant is N-terminally truncated and modified to pyroglutamate (pE-Abeta). Cell biological and animal experimental studies imply the catalysis of this modification by the enzyme glutaminyl cyclase (QC). However, direct histopathological evidence in transgenic animals from comparative brain region and cell type-specific expression of transgenic hAPP and QC, on the one hand, and on the formation of pE-Abeta aggregates, on the other, is lacking. Here, using single light microscopic, as well as triple immunofluorescent, labeling, we report the deposition of pE-Abeta only in the brain regions of APP-transgenic Tg2576 mice with detectable human APP and endogenous QC expression, such as the hippocampus, piriform cortex, and amygdala. Brain regions showing human APP expression without the concomitant presence of QC (the anterodorsal thalamic nucleus and perifornical nucleus) do not display pE-Abeta plaque formation. However, we also identified brain regions with substantial expression of human APP and QC in the absence of pE-Abeta deposition (the Edinger-Westphal nucleus and locus coeruleus). In these brain regions, the enzymes required to generate N-truncated Abeta peptides as substrates for QC might be lacking. Our observations provide additional evidence for an involvement of QC in AD pathogenesis via QC-catalyzed pE-Abeta formation. Full article
(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)
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16 pages, 10302 KiB  
Article
Time-Course Investigation of Small Molecule Metabolites in MAP-Stored Red Blood Cells Using UPLC-QTOF-MS
by Yong Zhou, Zhiyun Meng, Hui Gan, Ying Zheng, Xiaoxia Zhu, Zhuona Wu, Jian Li, Ruolan Gu and Guifang Dou
Molecules 2018, 23(4), 923; https://doi.org/10.3390/molecules23040923 - 16 Apr 2018
Cited by 6 | Viewed by 4537
Abstract
Red blood cells (RBCs) are routinely stored for 35 to 42 days in most countries. During storage, RBCs undergo biochemical and biophysical changes known as RBC storage lesion, which is influenced by alternative storage additive solutions (ASs). Metabolomic studies have been completed on [...] Read more.
Red blood cells (RBCs) are routinely stored for 35 to 42 days in most countries. During storage, RBCs undergo biochemical and biophysical changes known as RBC storage lesion, which is influenced by alternative storage additive solutions (ASs). Metabolomic studies have been completed on RBCs stored in a number of ASs, including SAGM, AS-1, AS-3, AS-5, AS-7, PAGGGM, and MAP. However, the reported metabolome analysis of laboratory-made MAP-stored RBCs was mainly focused on the time-dependent alterations in glycolytic intermediates during storage. In this study, we investigated the time-course of alterations in various small molecule metabolites in RBCs stored in commercially used MAP for 49 days using ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS). These alterations indicated that RBC storage lesion is related to multiple pathways including glycolysis, pentose phosphate pathway, glutathione homeostasis, and purine metabolism. Thus, our findings might be useful for understanding the complexity of metabolic mechanisms of RBCs in vitro aging and encourage the deployment of systems biology methods to blood products in transfusion medicine. Full article
(This article belongs to the Section Bioorganic Chemistry)
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13 pages, 4235 KiB  
Review
Recent Developments in C–H Activation for Materials Science in the Center for Selective C–H Activation
by Junxiang Zhang, Lauren J. Kang, Timothy C. Parker, Simon B. Blakey, Christine K. Luscombe and Seth R. Marder
Molecules 2018, 23(4), 922; https://doi.org/10.3390/molecules23040922 - 16 Apr 2018
Cited by 46 | Viewed by 7907
Abstract
Organic electronics is a rapidly growing field driven in large part by the synthesis of π-conjugated molecules and polymers. Traditional aryl cross-coupling reactions such as the Stille and Suzuki have been used extensively in the synthesis of π-conjugated molecules and polymers, but the [...] Read more.
Organic electronics is a rapidly growing field driven in large part by the synthesis of π-conjugated molecules and polymers. Traditional aryl cross-coupling reactions such as the Stille and Suzuki have been used extensively in the synthesis of π-conjugated molecules and polymers, but the synthesis of intermediates necessary for traditional cross-couplings can include multiple steps with toxic and hazardous reagents. Direct arylation through C–H bond activation has the potential to reduce the number of steps and hazards while being more atom-economical. Within the Center for Selective C–H Functionalization (CCHF), we have been developing C–H activation methodology for the synthesis of π-conjugated materials of interest, including direct arylation of difficult-to-functionalize electron acceptor intermediates and living polymerization of π-conjugated polymers through C–H activation. Full article
(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)
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13 pages, 6957 KiB  
Article
Gold Nanoparticles Grafted with PLL-b-PNIPAM: Interplay on Thermal/pH Dual-Response and Optical Properties
by Hui-Juan Li, Peng-Yun Li, Li-Ying Li, Abdul Haleem and Wei-Dong He
Molecules 2018, 23(4), 921; https://doi.org/10.3390/molecules23040921 - 16 Apr 2018
Cited by 13 | Viewed by 5897
Abstract
Narrowly distributed poly(l-lysine-b-N-isopropylacrylamide) (PLL-b-PNIPAM) was prepared through ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N-carboxy-α-amino anhydride and atom transfer radical polymerization of NIPAM, followed with the removal of ε-benzyloxycarbonyl group. Then gold nanoparticles (AuNPs) grafted [...] Read more.
Narrowly distributed poly(l-lysine-b-N-isopropylacrylamide) (PLL-b-PNIPAM) was prepared through ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N-carboxy-α-amino anhydride and atom transfer radical polymerization of NIPAM, followed with the removal of ε-benzyloxycarbonyl group. Then gold nanoparticles (AuNPs) grafted with PLL-b-PNIPAM (PNIPAM-PLL-AuNPs) were obtained by the reduction of chloroauric acid with sodium citrate in the presence of PLL-b-PNIPAM. PNIPAM-PLL-AuNPs and its precursors were thoroughly characterized by proton magnetic resonance spectroscope, Fourier transform infrared spectroscope, UV-vis spectroscope, transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, and circular dichroism. The obtained PNIPAM-PLL-AuNPs exhibited high colloid stability even at strong alkaline (pH = 12) and acidic (pH = 2) conditions. The thermal and pH dual-responsive behaviors of the grafting PLL-b-PNIPAM chains was observed to be affected by AuNPs, while not for the secondary structure of PLL chains. Correspondingly, the surface plasmon resonance (SPR) of AuNPs was found to be sensitive to both pH value and temperature. A blue shift in the SPR happened both with increasing pH value and increasing temperature. The stimuli-response was reversible in heating-cooling cycles. The gold nanoparticles with both pH and temperature response may have potential applications in biomedical areas and biosensors. Full article
(This article belongs to the Special Issue Stimuli-Responsive Polymeric Materials)
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13 pages, 3793 KiB  
Article
In Vitro Inhibitory Effects of Synthetic Cannabinoid EAM-2201 on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes
by Tae Yeon Kong, Soon-Sang Kwon, Jae Chul Cheong, Hee Seung Kim, Jin Young Kim and Hye Suk Lee
Molecules 2018, 23(4), 920; https://doi.org/10.3390/molecules23040920 - 16 Apr 2018
Cited by 7 | Viewed by 4556
Abstract
EAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid receptors that is widely abused as an illicit recreational drug in combination with other drugs. To evaluate the potential of EAM-2201 as a perpetrator of drug–drug interactions, the inhibitory effects of EAM-2201 [...] Read more.
EAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid receptors that is widely abused as an illicit recreational drug in combination with other drugs. To evaluate the potential of EAM-2201 as a perpetrator of drug–drug interactions, the inhibitory effects of EAM-2201 on major drug-metabolizing enzymes, cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were evaluated in pooled human liver microsomes using liquid chromatography–tandem mass spectrometry (LC-MS/MS). EAM-2201 at doses up to 50 µM negligibly inhibited the activities of eight major human CYPs (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and five UGTs (1A1, 1A4, 1A6, 1A9 and 2B7) in human liver microsomes. EAM-2201 exhibited time-dependent inhibition of CYP2C8-catalyzed amodiaquine N-deethylation, CYP2C9-catalyzed diclofenac 4′-hydroxylation, CYP2C19-catalyzed [S]-mephenytoin 4′-hydroxylation and CYP3A4-catalyzed midazolam 1′-hydroxylation with Ki values of 0.54 µM (kinact: 0.0633 min−1), 3.0 µM (kinact: 0.0462 min−1), 3.8 µM (kinact: 0.0264 min−1) and 4.1 µM (kinact: 0.0250 min−1), respectively and competitively inhibited UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation, with a Ki value of 2.4 µM. Based on these in vitro results, we conclude that EAM-2201 has the potential to trigger in vivo pharmacokinetic drug interactions when co-administered with substrates of CYP2C8, CYP2C9, CYP2C19, CYP3A4 and UGT1A3. Full article
(This article belongs to the Special Issue Emerging Topics in (Endo)Cannabinoid Signalling)
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12 pages, 1646 KiB  
Communication
The Stability of Medicinal Plant microRNAs in the Herb Preparation Process
by Wenyan Xie and Matthias F. Melzig
Molecules 2018, 23(4), 919; https://doi.org/10.3390/molecules23040919 - 16 Apr 2018
Cited by 41 | Viewed by 5399
Abstract
Herbal medicine is now globally accepted as a valid alternative system of pharmaceutical therapies. Various studies around the world have been initiated to develop scientific evidence-based herbal therapies. Recently, the therapeutic potential of medicinal plant derived miRNAs has attracted great attraction. MicroRNAs have [...] Read more.
Herbal medicine is now globally accepted as a valid alternative system of pharmaceutical therapies. Various studies around the world have been initiated to develop scientific evidence-based herbal therapies. Recently, the therapeutic potential of medicinal plant derived miRNAs has attracted great attraction. MicroRNAs have been indicated as new bioactive ingredients in medicinal plants. However, the stability of miRNAs during the herbal preparation process and their bioavailability in humans remain unclear. Viscum album L. (European mistletoe) has been widely used in folk medicine for the treatment of cancer and cardiovascular diseases. Our previous study has indicated the therapeutic potential of mistletoe miRNAs by using bioinformatics tools. To evaluate the stability of these miRNAs, various mistletoe extracts that mimic the clinical medicinal use as well as traditional folk medicinal use were prepared. The mistletoe miRNAs including miR166a-3p, miR159a, miR831-5p, val-miR218 and val-miR11 were quantified by stem-loop qRT-PCR. As a result, miRNAs were detectable in the majority of the extracts, indicating that consumption of medicinal plant preparations might introduce miRNAs into mammals. The factors that might cause miRNA degradation include ultrasonic treatment, extreme heat, especially RNase treatment, while to be associated with plant molecules (e.g., proteins, exosomes) might be an efficient way to protect miRNAs against degradation. Our study confirmed the stability of plant derived miRNAs during herb preparations, suggesting the possibility of functionally intact medicinal plant miRNAs in mammals. Full article
(This article belongs to the Section Medicinal Chemistry)
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18 pages, 3439 KiB  
Review
Synthesis of Theaflavins and Their Functions
by Masumi Takemoto and Hiroaki Takemoto
Molecules 2018, 23(4), 918; https://doi.org/10.3390/molecules23040918 - 16 Apr 2018
Cited by 118 | Viewed by 11477
Abstract
Numerous epidemiological and interventional clinical studies have consistently reported that black tea is good for human health. The polyphenolic compound, theaflavin, and its galloyl esters (theaflavins) are the primary red pigments in black tea that possess several health benefits, including fat-reducing and glucose-lowering [...] Read more.
Numerous epidemiological and interventional clinical studies have consistently reported that black tea is good for human health. The polyphenolic compound, theaflavin, and its galloyl esters (theaflavins) are the primary red pigments in black tea that possess several health benefits, including fat-reducing and glucose-lowering capabilities and lifestyle-related disease prevention related to anti-obesity, anticancer, anti-atherosclerotic, anti-inflammatory, antiviral, antibacterial, anti-osteoporotic, and anti-dental caries properties. These compounds are produced by key enzymes, such as polyphenol oxidase and peroxidase, from parent green tea catechins present in fresh green tea leaves during the production of black tea leaves or the fermentation of green tea. However, theaflavins are only present in low concentrations in black tea; thus, their extraction from black tea leaves at sufficient levels for use in medical studies has been difficult. To circumvent this issue, different procedures for the synthesis of theaflavins using chemical oxidizing reagents or enzymes have been studied; however, low yields have limited their utility. Recently, however, several biosynthetic methods have been developed for the mass production of theaflavins. Using these methods, the physiological functions of theaflavins in lifestyle-related diseases in mice and humans have also been studied. In this review, we present the synthesis of theaflavins and their health benefits. Full article
(This article belongs to the Special Issue Catechin in Human Health and Disease)
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16 pages, 31187 KiB  
Article
A Comparative Genomic Survey Provides Novel Insights into Molecular Evolution of l-Aromatic Amino Acid Decarboxylase in Vertebrates
by Yanping Li, Yunyun Lv, Chao Bian, Xinxin You, Li Deng and Qiong Shi
Molecules 2018, 23(4), 917; https://doi.org/10.3390/molecules23040917 - 16 Apr 2018
Cited by 8 | Viewed by 4756
Abstract
Melatonin is a pleiotropic molecule with various important physiological roles in vertebrates. l-aromatic amino acid decarboxylase (AAAD) is the second enzyme for melatonin synthesis. By far, a clear-cut gene function of AAAD in the biosynthesis of melatonin has been unclear in vertebrates. [...] Read more.
Melatonin is a pleiotropic molecule with various important physiological roles in vertebrates. l-aromatic amino acid decarboxylase (AAAD) is the second enzyme for melatonin synthesis. By far, a clear-cut gene function of AAAD in the biosynthesis of melatonin has been unclear in vertebrates. Here, we provide novel insights into the evolution of AAAD based on 77 vertebrate genomes. According to our genome-wide alignments, we extracted a total of 151 aaad nucleotide sequences. A phylogenetic tree was constructed on the basis of these sequences and corresponding protein alignments, indicating that tetrapods and diploid bony fish genomes contained one aaad gene and a new aaad-like gene, which formed a novel AAAD family. However, in tetraploid teleosts, there were two copies of the aaad gene due to whole genome duplication. A subsequent synteny analysis investigated 81 aaad sequences and revealed their collinearity and systematic evolution. Interestingly, we discovered that platypus (Ornithorhynchus anatinus), Atlantic cod (Guadus morhua), Mexican tetra (Astyanax mexicanus), and a Sinocyclocheilus cavefish (S. anshuiensis) have long evolutionary branches in the phylogenetic topology. We also performed pseudogene identification and selection pressure analysis; however, the results revealed a deletion of 37 amino acids in Atlantic cod and premature stop codons in the cave-restricted S. anshuiensis and A. mexicanus, suggesting weakening or disappearing rhythms in these cavefishes. Selective pressure analysis of aaad between platypus and other tetrapods showed that rates of nonsynonymous (Ka) and synonymous (Ks) substitutions were higher when comparing the platypus to other representative tetrapods, indicating that, in this semiaquatic mammal, the aaad gene experienced selection during the process of evolution. In summary, our current work provides novel insights into aaad genes in vertebrates from a genome-wide view. Full article
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12 pages, 6167 KiB  
Article
Cultivar and Harvest Month Influence the Nutrient Content of Opuntia spp. Cactus Pear Cladode Mucilage Extracts
by Alba Du Toit, Maryna De Wit and Arno Hugo
Molecules 2018, 23(4), 916; https://doi.org/10.3390/molecules23040916 - 16 Apr 2018
Cited by 47 | Viewed by 5456
Abstract
Mucilage extracted from cactus pear cladodes is a hydrocolloid gum. It is a novel, natural, low-kilojoule, cost-effective texture-modifying ingredient in functional food products. Yet, the cultivar with the most optimal nutrient content and the preferred harvest times are as yet unknown. For this [...] Read more.
Mucilage extracted from cactus pear cladodes is a hydrocolloid gum. It is a novel, natural, low-kilojoule, cost-effective texture-modifying ingredient in functional food products. Yet, the cultivar with the most optimal nutrient content and the preferred harvest times are as yet unknown. For this reason, mucilage from three Opuntia ficus-indica (Algerian, Morado and Gymno-Carpo) and one Opuntia robusta (Robusta) cultivar were investigated to determine their nutrient content over six months. Nutrients that contribute energy (10.2 kJ/g) were low. The mineral content was high (ash 17.7/100 g), particularly calcium (3.0 g/100 g) and phosphorous (109.5 mg/kg). Low insoluble acid-detergent fibre (1.4 g/kg) and neutral-detergent fibre (2.1 g/kg) values indicated that mucilage was mostly soluble fibre. Calcium oxalate crystals were not detected in dried mucilage. Opuntia robusta powders had higher protein, extractable fat and potassium content, while Opuntia ficus-indica mucilage powders had higher polyunsaturated (Linoleic and α-Linolenic acid) fat content. O. robusta Robusta mucilage, harvested after the fruit harvest (February) had the lowest energy content and the highest mineral and protein content. Mucilage powders were highly soluble, low-kilojoule and mineral-rich. This is a functional ingredient that is produced from an easily cultivated crop, as cactus pears grow in areas with poor soil, extremely high daytime temperatures and limited water supplies. Full article
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3 pages, 156 KiB  
Editorial
Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis
by Jiawei Chen, Miao Hong and Eugene Y.-X. Chen
Molecules 2018, 23(4), 915; https://doi.org/10.3390/molecules23040915 - 16 Apr 2018
Cited by 2 | Viewed by 4184
11 pages, 1157 KiB  
Communication
One-Pot, Highly Stereoselective Synthesis of Dithioacetal-α,α-Diglycosides
by Maria F. Céspedes Dávila, Jérémy P. Schneider, Amélie Godard, Damien Hazelard and Philippe Compain
Molecules 2018, 23(4), 914; https://doi.org/10.3390/molecules23040914 - 15 Apr 2018
Cited by 11 | Viewed by 5642
Abstract
A one-step access to dithioacetal-α,α-diglycosides is reported. The synthetic strategy is based on the thioacetalization of aldehydes or ketones via highly stereoselective ring-opening of 1,6 anhydrosugars with bis(trimethylsilyl)sulfide. Full article
(This article belongs to the Special Issue Glycomimetics: Design, Synthesis and Therapeutic Applications)
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15 pages, 21559 KiB  
Article
Poly(vinyl Chloride) Photostabilization in the Presence of Schiff Bases Containing a Thiadiazole Moiety
by Naser Shaalan, Nawres‎‏ Laftah, Gamal A. El-Hiti, Mohammad Hayal Alotaibi, Raad Muslih, Dina S. Ahmed and Emad Yousif
Molecules 2018, 23(4), 913; https://doi.org/10.3390/molecules23040913 - 15 Apr 2018
Cited by 51 | Viewed by 4741
Abstract
Five Schiff bases containing a thiadiazole moiety have been used as poly(vinyl chloride) photostabilizers at low concentrations. The efficiency of Schiff bases as photostabilizers was investigated using various techniques, for example, the changes in poly(vinyl chloride) infrared spectra, molecular weight, chain scission quantum [...] Read more.
Five Schiff bases containing a thiadiazole moiety have been used as poly(vinyl chloride) photostabilizers at low concentrations. The efficiency of Schiff bases as photostabilizers was investigated using various techniques, for example, the changes in poly(vinyl chloride) infrared spectra, molecular weight, chain scission quantum yield, and surface morphology were monitored upon irradiation with an ultraviolet light. Evidently, all the additives used inhibited poly(vinyl chloride) photodegradation at a significant level. The most efficient Schiff base exhibited a high level of aromaticity and contained a hydroxyl group. It seems possible that such photostabilization could be due to the direct absorption of ultraviolet radiation by the additives. In addition, Schiff bases could act as radical scavengers and proton transfer facilitators to stabilize the polymeric materials. Full article
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7 pages, 3768 KiB  
Article
Electrochemical Aptamer-Based Sensors for Rapid Point-of-Use Monitoring of the Mycotoxin Ochratoxin A Directly in a Food Stream
by Jacob Somerson and Kevin W. Plaxco
Molecules 2018, 23(4), 912; https://doi.org/10.3390/molecules23040912 - 15 Apr 2018
Cited by 40 | Viewed by 7318
Abstract
The ability to measure the concentration of specific small molecules continuously and in real-time in complex sample streams would impact many areas of agriculture, food safety, and food production. Monitoring for mycotoxin taint in real time during food processing, for example, could improve [...] Read more.
The ability to measure the concentration of specific small molecules continuously and in real-time in complex sample streams would impact many areas of agriculture, food safety, and food production. Monitoring for mycotoxin taint in real time during food processing, for example, could improve public health. Towards this end, we describe here an inexpensive electrochemical DNA-based sensor that supports real-time monitor of the mycotoxin ochratoxin A in a flowing stream of foodstuffs. Full article
(This article belongs to the Special Issue Nucleic Acid Aptamers)
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17 pages, 785 KiB  
Article
Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability
by Chen-Peng Chen, Chan-Cheng Chen, Chia-Wen Huang and Yen-Ching Chang
Molecules 2018, 23(4), 911; https://doi.org/10.3390/molecules23040911 - 15 Apr 2018
Cited by 88 | Viewed by 11185
Abstract
The skin permeability (Kp) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. [...] Read more.
The skin permeability (Kp) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR) based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical’s skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products 2018)
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