Biological Membranes as Targets for Natural and Synthetic Compounds

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Functions".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 22132

Special Issue Editor


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Guest Editor
Department of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University, São José do Rio Preto 15054-000, Brazil
Interests: membrane as drug targets; membrane bioassays; drug discovery; natural products; medicinal chemistry
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Special Issue Information

Dear Colleagues,

Biological membranes are responsible for all types of regulation and compound transfer as well as information flow between and within eukaryotic and prokaryotic cells. Plasma membrane is also involved in both the generation and receipt of chemical and electrical signals, cell adhesion, which is responsible for tissue or biofilm information, cell locomotion, biochemical reactions, and cell reproduction. Internal membranes have similar properties and, in addition, are often actively involved in organelle functions. In this context, membranes play a key role in maintaining cell integrity, and their involvement in cellular function makes these regions of cells potential targets for bioactive compounds. This Special Issue is devoted to state-of-the-art research on topics concerning the discovery and development of natural and synthetic compounds that act on biological membranes, including their lipid, protein, and carbohydrate components. This covers all the aspects associated to the isolation of natural products, synthesis of compounds and bioassays that elucidate a mode action on membrane, and their components. 

Prof. Dr. Luis Octavio Regasini
Guest Editor

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Keywords

  • Membrane
  • Natural product
  • Medicinal chemistry
  • Target
  • Drug discovery
  • Drug development
  • Synthesis

Published Papers (8 papers)

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Editorial

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3 pages, 202 KiB  
Editorial
Biological Membranes as Targets for Natural and Synthetic Compounds
by Luis Octavio Regasini
Membranes 2022, 12(12), 1172; https://doi.org/10.3390/membranes12121172 - 22 Nov 2022
Cited by 1 | Viewed by 888
Abstract
Biological membranes are responsible for all types of regulation and compound transfer, as well as information flow between and within eukaryotic and prokaryotic cells [...] Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)

Research

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12 pages, 1598 KiB  
Article
Antibacterial Activity of Isobavachalcone (IBC) Is Associated with Membrane Disruption
by Leticia Ribeiro de Assis, Reinaldo dos Santos Theodoro, Maria Beatriz Silva Costa, Julyanna Andrade Silva Nascentes, Miguel Divino da Rocha, Meliza Arantes de Souza Bessa, Ralciane de Paula Menezes, Guilherme Dilarri, Giovane Böerner Hypolito, Vanessa Rodrigues dos Santos, Cristiane Duque, Henrique Ferreira, Carlos Henrique Gomes Martins and Luis Octavio Regasini
Membranes 2022, 12(3), 269; https://doi.org/10.3390/membranes12030269 - 25 Feb 2022
Cited by 15 | Viewed by 2869
Abstract
Isobavachalcone (IBC) is a natural prenylated chalcone with a broad spectrum of pharmacological properties. In this work, we newly synthesized and investigated the antibacterial activity of IBC against Gram-positive, Gram-negative and mycobacterial species. IBC was active against Gram-positive bacteria, mainly against [...] Read more.
Isobavachalcone (IBC) is a natural prenylated chalcone with a broad spectrum of pharmacological properties. In this work, we newly synthesized and investigated the antibacterial activity of IBC against Gram-positive, Gram-negative and mycobacterial species. IBC was active against Gram-positive bacteria, mainly against Methicillin-Susceptible Staphylococcus aureus (MSSA) and Methicillin-Resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentration (MIC) values of 1.56 and 3.12 µg/mL, respectively. On the other hand, IBC was not able to act against Gram-negative species (MIC > 400 µg/mL). IBC displayed activity against mycobacterial species (MIC = 64 µg/mL), including Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium kansasii. IBC was able to inhibit more than 50% of MSSA and MRSA biofilm formation at 0.78 µg/mL. Its antibiofilm activity was similar to vancomycin, which was active at 0.74 µg/mL. In order to study the mechanism of the action by fluorescence microscopy, the propidium iodide (PI) and SYTO9 fluorophores indicated that IBC disrupted the membrane of Bacillus subtilis. Toxicity assays using human keratinocytes (HaCaT cell line) showed that IBC did not have the capacity to reduce the cell viability. These results suggested that IBC is a promising antibacterial agent with an elucidated mode of action and potential applications as an antibacterial drug and a medical device coating. Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)
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20 pages, 2538 KiB  
Article
Surface Properties of Synaptosomes in the Presence of L-Glutamic and Kainic Acids: In Vitro Alteration of the ATPase and Acetylcholinesterase Activities
by Virjinia Doltchinkova, Nevena Mouleshkova and Victoria Vitkova
Membranes 2021, 11(12), 987; https://doi.org/10.3390/membranes11120987 - 17 Dec 2021
Cited by 2 | Viewed by 2502
Abstract
Morphologically and functionally identical to brain synapses, the nerve ending particles synaptosomes are biochemically derived membrane structures responsible for the transmission of neural information. Their surface and mechanical properties, measured in vitro, provide useful information about the functional activity of synapses in the [...] Read more.
Morphologically and functionally identical to brain synapses, the nerve ending particles synaptosomes are biochemically derived membrane structures responsible for the transmission of neural information. Their surface and mechanical properties, measured in vitro, provide useful information about the functional activity of synapses in the brain in vivo. Glutamate and kainic acid are of particular interest because of their role in brain pathology (including causing seizure, migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, traumatic brain injury and stroke). The effects of the excitatory neurotransmitter L-glutamic acid and its agonist kainic acid are tested on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic membranes prepared from the cerebral cortex of rat brain tissue. The surface parameters of synaptosome preparations from the cerebral cortex in the presence of L-glutamic and kainic acids are studied by microelectrophoresis for the first time. The studied neurotransmitters promote a significant increase in the electrophoretic mobility and surface electrical charge of synaptosomes at 1–4 h after isolation. The measured decrease in the bending modulus of model bimolecular membranes composed of monounsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine provides evidence for softer membranes in the presence of L-glutamate. Kainic acid does not affect membrane mechanical stability even at ten-fold higher concentrations. Both the L-glutamic and kainic acids reduce acetylcholinesterase activity and deviation from the normal functions of neurotransmission in synapses is presumed. The presented results regarding the modulation of the enzyme activity of synaptic membranes and surface properties of synaptosomes are expected by biochemical and biophysical studies to contribute to the elucidation of the molecular mechanisms of neurotransmitters/agonists’ action on membranes. Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)
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18 pages, 2180 KiB  
Article
Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of Bioactive Compounds
by Ane Elexpe, Nerea Nieto, Claudia Fernández-Cuétara, Celtia Domínguez-Fernández, Teresa Morera-Herreras, María Torrecilla, Cristina Miguélez, Antonio Laso, Eneko Ochoa, María Bailen, Azucena González-Coloma, Iñigo Angulo-Barturen, Egoitz Astigarraga and Gabriel Barreda-Gómez
Membranes 2021, 11(12), 943; https://doi.org/10.3390/membranes11120943 - 29 Nov 2021
Cited by 6 | Viewed by 2463
Abstract
The production of reactive oxygen species (ROS) increases considerably in situations of cellular stress, inducing lipid peroxidation and multiple alterations in proteins and nucleic acids. However, sensitivity to oxidative damage varies between organs and tissues depending on the triggering process. Certain drugs used [...] Read more.
The production of reactive oxygen species (ROS) increases considerably in situations of cellular stress, inducing lipid peroxidation and multiple alterations in proteins and nucleic acids. However, sensitivity to oxidative damage varies between organs and tissues depending on the triggering process. Certain drugs used in the treatment of diverse diseases such as malaria have side effects similar to those produced by oxidative damage, although no specific study has been conducted. For this purpose, cell membrane microarrays were developed and the superoxide production evoked by the mitochondrial activity was assayed in the presence of specific inhibitors: rotenone, antimycin A and azide. Once the protocol was set up on cell membrane isolated from rat brain areas, the effect of six antimalarial drugs (atovaquone, quinidine, doxycycline, mefloquine, artemisinin, and tafenoquine) and two essential oils (Rosmarinus officinalis and Origanum majoricum) were evaluated in multiple human samples. The basal activity was different depending on the type of tissue, the liver, jejunum and adrenal gland being the ones with the highest amount of superoxide. The antimalarial drugs studied showed specific behavior according to the type of human tissue analyzed, with atovaquone and quinidine producing the highest percentage of superoxide formation, and doxycycline the lowest. In conclusion, the analysis of superoxide production evaluated in cell membranes of a collection of human tissues allowed for the characterization of the safety profile of these antimalarial drugs against toxicity mediated by oxidative stress. Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)
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13 pages, 1582 KiB  
Article
Multidrug Resistance Like Protein 1 Activity in Malpighian Tubules Regulates Lipid Homeostasis in Drosophila
by Wen Liu, Hao Cao, Moses Kimari, Georgios Maronitis, Michael J. Williams and Helgi B Schiöth
Membranes 2021, 11(6), 432; https://doi.org/10.3390/membranes11060432 - 8 Jun 2021
Cited by 3 | Viewed by 2751
Abstract
Multidrug resistance proteins (MRPs), members of the ATP-binding cassette transporter (ABC transporter) family, are pivotal for transporting endo- and xenobiotics, which confer resistance to anticancer agents and contribute to the clearance of oxidative products. However, their function in many biological processes is still [...] Read more.
Multidrug resistance proteins (MRPs), members of the ATP-binding cassette transporter (ABC transporter) family, are pivotal for transporting endo- and xenobiotics, which confer resistance to anticancer agents and contribute to the clearance of oxidative products. However, their function in many biological processes is still unclear. We investigated the role of an evolutionarily conserved MRP in metabolic homeostasis by knocking down the expression of Drosophila multidrug-resistance like protein 1 (MRP) in several tissues involved in regulating metabolism, including the gut, fat body, and Malpighian tubules. Interestingly, only suppression of MRP in the Malpighian tubules, the functional equivalent to the human kidney, was sufficient to cause abnormal lipid accumulation and disrupt feeding behavior. Furthermore, reduced Malpighian tubule MRP expression resulted in increased Hr96 (homolog of human pregnane X receptor) expression. Hr96 is known to play a role in detoxification and lipid metabolism processes. Reduced expression of MRP in the Malpighian tubules also conveyed resistance to oxidative stress, as well as reduced normal levels of reactive oxygen species in adult flies. This study reveals that an evolutionarily conserved MRP is required in Drosophila Malpighian tubules for proper metabolic homeostasis. Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)
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17 pages, 1985 KiB  
Article
Differential Antimicrobial Effect of Essential Oils and Their Main Components: Insights Based on the Cell Membrane and External Structure
by Sergio Andrade-Ochoa, Karla Fabiola Chacón-Vargas, Luvia Enid Sánchez-Torres, Blanca Estela Rivera-Chavira, Benjamín Nogueda-Torres and Guadalupe Virginia Nevárez-Moorillón
Membranes 2021, 11(6), 405; https://doi.org/10.3390/membranes11060405 - 28 May 2021
Cited by 33 | Viewed by 4824
Abstract
The biological activity of essential oils and their major components is well documented. Essential oils such as oregano and cinnamon are known for their effect against bacteria, fungi, and even viruses. The mechanism of action is proposed to be related to membrane and [...] Read more.
The biological activity of essential oils and their major components is well documented. Essential oils such as oregano and cinnamon are known for their effect against bacteria, fungi, and even viruses. The mechanism of action is proposed to be related to membrane and external cell structures, including cell walls. This study aimed to evaluate the biological activity of seven essential oils and eight of their major components against Gram-negative and Gram-positive bacteria, filamentous fungi, and protozoans. The antimicrobial activity was evaluated by determination of the Minimal Inhibitory Concentration for Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Salmonella Typhimurium, Shigella sonnei, Aspergillus niger, Aspergillus ochraceus, Alternaria alternata, and Fusarium oxysporium, the half-maximal inhibitory concentration (IC50) for Trypanosoma cruzi and Leishmania mexicana, and the median lethal dose (LD50) for Giardia lamblia. Results showed that oregano essential oil showed the best antibacterial activity (66–100 µg/mL), while cinnamon essential oil had the best fungicidal activity (66–116 µg/mL), and both showed excellent antiprotozoal activity (22–108 µg/mL). Regarding the major components, thymol and carvacrol were also good antimicrobials (23–200 µg/mL), and cinnamaldehyde was an antifungal compound (41–75 µg/mL). The major components were grouped according to their chemical structure as phenylpropanoids, terpenoids, and terpinenes. The statistical analysis of the grouped data demonstrated that protozoans were more susceptible to the essential oils, followed by fungi, Gram-positive bacteria, and Gram-negative bacteria. The analysis for the major components showed that the most resistant microbial group was fungi, which was followed by bacteria, and protozoans were also more susceptible. Principal Component Analysis for the essential oils demonstrated the relationship between the biological activity and the microbial group tested, with the first three components explaining 94.3% of the data variability. The chemical structure of the major components was also related to the biological activity presented against the microbial groups tested, where the three first principal components accounted for 91.9% of the variability. The external structures and the characteristics of the cell membranes in the different microbial groups are determinant for their susceptibility to essential oils and their major components Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)
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11 pages, 13759 KiB  
Article
The Bacteriostatic Activity of 2-Phenylethanol Derivatives Correlates with Membrane Binding Affinity
by Isabel S. Kleinwächter, Stefanie Pannwitt, Alessia Centi, Nadja Hellmann, Eckhard Thines, Tristan Bereau and Dirk Schneider
Membranes 2021, 11(4), 254; https://doi.org/10.3390/membranes11040254 - 31 Mar 2021
Cited by 14 | Viewed by 2138
Abstract
The hydrophobic tails of aliphatic primary alcohols do insert into the hydrophobic core of a lipid bilayer. Thereby, they disrupt hydrophobic interactions between the lipid molecules, resulting in a decreased lipid order, i.e., an increased membrane fluidity. While aromatic alcohols, such as 2-phenylethanol, [...] Read more.
The hydrophobic tails of aliphatic primary alcohols do insert into the hydrophobic core of a lipid bilayer. Thereby, they disrupt hydrophobic interactions between the lipid molecules, resulting in a decreased lipid order, i.e., an increased membrane fluidity. While aromatic alcohols, such as 2-phenylethanol, also insert into lipid bilayers and disturb the membrane organization, the impact of aromatic alcohols on the structure of biological membranes, as well as the potential physiological implication of membrane incorporation has only been studied to a limited extent. Although diverse targets are discussed to be causing the bacteriostatic and bactericidal activity of 2-phenylethanol, it is clear that 2-phenylethanol severely affects the structure of biomembranes, which has been linked to its bacteriostatic activity. Yet, in fungi some 2-phenylethanol derivatives are also produced, some of which appear to also have bacteriostatic activities. We showed that the 2-phenylethanol derivatives phenylacetic acid, phenyllactic acid, and methyl phenylacetate, but not Tyrosol, were fully incorporated into model membranes and affected the membrane organization. Furthermore, we observed that the propensity of the herein-analyzed molecules to partition into biomembranes positively correlated with their respective bacteriostatic activity, which clearly linked the bacteriotoxic activity of the substances to biomembranes. Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)
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Review

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12 pages, 627 KiB  
Review
A Review: Natural and Synthetic Compounds Targeting Entamoeba histolytica and Its Biological Membrane
by Nurhana Jasni, Syazwan Saidin, Norsyahida Arifin, Daruliza Kernain Azman, Lai Ngit Shin and Nurulhasanah Othman
Membranes 2022, 12(4), 396; https://doi.org/10.3390/membranes12040396 - 1 Apr 2022
Cited by 3 | Viewed by 2592
Abstract
Amoebiasis is the third most common parasitic cause of morbidity and mortality, particularly in countries with poor hygienic settings in central and south America, Africa, and India. This disease is caused by a protozoan parasite, namely Entamoeba histolytica, which infects approximately 50 [...] Read more.
Amoebiasis is the third most common parasitic cause of morbidity and mortality, particularly in countries with poor hygienic settings in central and south America, Africa, and India. This disease is caused by a protozoan parasite, namely Entamoeba histolytica, which infects approximately 50 million people worldwide, resulting in 70,000 deaths every year. Since the 1960s, E. histolytica infection has been successfully treated with metronidazole. However, there are drawbacks to metronidazole therapy: the side effects, duration of treatment, and need for additional drugs to prevent transmission. Previous interdisciplinary studies, including biophysics, bioinformatics, chemistry, and, more recently, lipidomics studies, have increased biomembranes’ publicity. The biological membranes are comprised of a mixture of membrane and cytosolic proteins. They work hand in hand mainly at the membrane part. They act as dedicated platforms for a whole range of cellular processes, such as cell proliferation, adhesion, migration, and intracellular trafficking, thus are appealing targets for drug treatment. Therefore, this review aims to observe the updated trend of the research regarding the biological membranes of E. histolytica from 2015 to 2021, which may help further research regarding the drug targeting the biological membrane. Full article
(This article belongs to the Special Issue Biological Membranes as Targets for Natural and Synthetic Compounds)
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