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Future Pharmacol., Volume 2, Issue 3 (September 2022) – 12 articles

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17 pages, 1116 KiB  
Review
Strategies for Generating Human Pluripotent Stem Cell-Derived-Organoid Culture for Disease Modeling, Drug Screening, and Regenerative Therapy
by Zakiya Gania, Syarifah Tiara Noorintan, Ni Putu Diah Pradnya Septiari, Dhea Sandra Fitriany and Fuad Gandhi Torizal
Future Pharmacol. 2022, 2(3), 360-376; https://doi.org/10.3390/futurepharmacol2030025 - 05 Sep 2022
Cited by 5 | Viewed by 3912
Abstract
Human pluripotent stem cells (hPSCs) have become a powerful tool to generate the various kinds of cell types comprising the human body. Recently, organoid technology has emerged as a platform to generate a physiologically relevant tissue-like structure from PSCs. Compared to an actual [...] Read more.
Human pluripotent stem cells (hPSCs) have become a powerful tool to generate the various kinds of cell types comprising the human body. Recently, organoid technology has emerged as a platform to generate a physiologically relevant tissue-like structure from PSCs. Compared to an actual human organ, this structure more closely represents a three-dimensional microenvironment than the conventional monolayer culture system for transplantation, disease modeling, and drug development. Despite its advantages, however, the organoid culture system still has various problems related to culture methods, which have become a challenge for attempts to obtain similar physiological properties to their original tissue counterparts. Here, we discuss the current development of organoid culture methods, including the problems that may arise from the currently available culture systems, as well as a possible approach for overcoming their current limitations and improving their optimum utilization for translational application purposes. Full article
(This article belongs to the Special Issue Three-Dimensional In Vitro Cell Culture Models in Drug Discovery)
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13 pages, 1086 KiB  
Review
The Influence of Cannabinoids on Multiple Myeloma Cells: A Scoping Review
by Karan Varshney, Prerana Ghosh and Akash Patel
Future Pharmacol. 2022, 2(3), 347-359; https://doi.org/10.3390/futurepharmacol2030024 - 02 Sep 2022
Viewed by 5970
Abstract
Multiple myeloma (MM) is one of the most common hematological malignancies. There is a clear need for research into new treatment options that can improve the life expectancy and quality of life for MM patients; this is particularly salient for those with relapsed/refractory [...] Read more.
Multiple myeloma (MM) is one of the most common hematological malignancies. There is a clear need for research into new treatment options that can improve the life expectancy and quality of life for MM patients; this is particularly salient for those with relapsed/refractory disease. Cannabinoids (CB) have shown potential in treatment regimens for a number of cancers, but little is currently known about their effectiveness against MM. Hence, we conducted a scoping review regarding the usage of CB against MM cells. For our review, searches were conducted in PubMed, Web of Science, and OVID Medline. After screening, six articles were eligible for inclusion, all of which were laboratory studies. It was demonstrated that CB decrease MM cell viability, and this was consistently shown to occur alongside the activation of apoptotic pathways in MM cells. These effects were shown to continue to occur in dexamethasone-resistant MM cells. The effects of CB on MM cells were enhanced when used in combination with standard treatments for MM. Critically, these marked decreases in MM cell viability induced by CB did not occur in non-MM cells. Overall, these findings indicate a clear need for future clinical trials of the integration of CB into MM treatment regimens. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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17 pages, 2283 KiB  
Article
The Charge and Phase State of Liposomes Dramatically Affects the Binding of Mannosylated Chitosan
by Irina M. Le-Deygen, Viktoria V. Rokosovina, Anna A. Skuredina, Ivan D. Yakimov and Elena V. Kudryashova
Future Pharmacol. 2022, 2(3), 330-346; https://doi.org/10.3390/futurepharmacol2030023 - 01 Sep 2022
Cited by 5 | Viewed by 1851
Abstract
Liposomal complexes with mucoadhesive polymers, e.g., mannosylated chitosan, are considered as prospective antituberculosis drug delivery systems. The properties of such complexes can be critically affected by the charge and phase state of liposomes. The aim of our work was to study the interaction [...] Read more.
Liposomal complexes with mucoadhesive polymers, e.g., mannosylated chitosan, are considered as prospective antituberculosis drug delivery systems. The properties of such complexes can be critically affected by the charge and phase state of liposomes. The aim of our work was to study the interaction of mannosylated chitosan with liposomes of various compositions and to identify the key patterns of this process. We tracked the interaction by titrating the liposomes with an increasing base-molar excess using the DLS method and ATR-FTIR spectroscopy. Sorption isotherms were obtained using ATR-FTIR spectroscopy and linearized in the Scatchard coordinates to evaluate the dissociation constant (Kdis). The inclusion of cardiolipin (CL) in the lipid composition helps to reduce the Kdis of the complexes by an order of magnitude of 3.8 × 10−4 M and 6.4 × 10−5 M for dipalmitoylphosphatidylcholine (DPPC) and DPPC:CL 80:20 (weight ratio), respectively. Preheating at 37 °C of gel-like anionic liposomes helps to reduce the Kdis to 3.5 × 10−5 M. Anionic liposomes, both in liquid crystal and in the gel-like state, form multipoint non-covalent complexes with chitosan–mannose conjugates due to the partial neutralization of the charges on the surface of the vesicles. Meanwhile, neutral liposomes in both states form unstable heterogeneous complexes, probably due to the predominant sorption of the polymer on the vesicles. Complex formation provides preferable binding with the model mannose-binding receptor concanavalin A and sustained pH-sensitive release of the antituberculosis drug moxifloxacin. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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10 pages, 1595 KiB  
Article
Bioactivity of Ionic Liquids Based on Valproate in SH-SY5Y Human Neuroblastoma Cell Line
by Ana Rita Dias, Ricardo Ferraz, João Costa-Rodrigues, Andreia F. M. Santos, Manuel L. Jacinto, Cristina Prudêncio, João Paulo Noronha, Luis C. Branco and Željko Petrovski
Future Pharmacol. 2022, 2(3), 320-329; https://doi.org/10.3390/futurepharmacol2030022 - 31 Aug 2022
Cited by 1 | Viewed by 1660
Abstract
The search for alternative and effective therapies to fight cancer is one of the main goals of the pharmaceutical industry. Recently, ionic liquids (ILs) have emerged as potential therapeutic agents with antitumor properties. The goal of this study was to synthesize and evaluate [...] Read more.
The search for alternative and effective therapies to fight cancer is one of the main goals of the pharmaceutical industry. Recently, ionic liquids (ILs) have emerged as potential therapeutic agents with antitumor properties. The goal of this study was to synthesize and evaluate the bioactivity of different ILs coupled with the active pharmaceutical ingredient (API) valproate (VPA) as an antitumor agent. The toxicity of the prepared ionic liquids was evaluated by the MTT cell metabolic assay in human neuroblastoma SH-SY5Y and human primary Gingival Fibroblast (GF) cell lines, in which they showed inhibitory effects during the study period. In addition, low cytotoxicity against GF cell lines was observed, suggesting that these compounds are not toxic to human cell lines. [C2OHDMiM][VPA] demonstrated an outstanding antitumor activity against SH-SY5Y and lower activity against the non-neoplastic GF line. The herein assessed compounds played an important role in the modulation of the signaling pathways involved in the cellular behavior. This work also highlights the potential of these ILs-API as possible antitumor agents. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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14 pages, 6014 KiB  
Article
A Computational Approach for Molecular Characterization of Covaxin (BBV152) and Its Ingredients for Assessing Its Efficacy against COVID-19
by Atala B. Jena and Asim K. Duttaroy
Future Pharmacol. 2022, 2(3), 306-319; https://doi.org/10.3390/futurepharmacol2030021 - 18 Aug 2022
Cited by 3 | Viewed by 1700
Abstract
SARS-CoV-2 vaccination is a life-saving strategy for the entire population living in this pandemic. Several vaccines were developed using different platforms such as nucleic acids, viral vectors recombinant proteins, live attenuated, and inactivated virus modalities, etc. Although immunogenicity and efficacy of these COVID [...] Read more.
SARS-CoV-2 vaccination is a life-saving strategy for the entire population living in this pandemic. Several vaccines were developed using different platforms such as nucleic acids, viral vectors recombinant proteins, live attenuated, and inactivated virus modalities, etc. Although immunogenicity and efficacy of these COVID vaccines were investigated, Covaxin (a vaccine code-named BBV152), an inactivated COVID-19 vaccine, has not been well studied yet. This study aimed to explore the interactions between biomolecules with vaccine adjuvants by analyzing molecular and protein–protein interactions of S protein, angiotensin-converting enzyme 2 (ACE2), and human serum albumin (HSA) with the ingredients of Covaxin (2-phenoxyethanol and imidazoquinolinone) by computational methods using Autodock Vina, Cluspro, and Swiss ADME. In addition, its drug-likeness property was investigated. The binding energies using Autodock Vina showed stronger interactions of 2-phenoxyethanol and imidazoquinolinone with viral surface protein, S protein, human cell membrane receptor ACE2, and drug carrier plasma HSA (−5.2, −5.3 and −5.3 kcal/mol; −8.5, −8.5 and −9.1 kcal/mol, respectively). The interaction between S protein with ACE2 in the presence of 2-phenoxyethanol and imidazoquinolinone hindered the S protein function by reducing the binding energy between these proteins. In addition, imidazoquinolinone may have the drug-likeness property based on pharmacokinetic and physicochemical parameters. These results suggest that the Covaxin vaccine, owing to these ingredients, may impart greater efficacy in averting the virus and thus it may be more effective in producing herd immunity. In conclusion, for the first time, this computational study predicts the possible useful effects of these two adjuvants of Covaxin in therapeutic and drug-likeness strategies against SARS-CoV-2. Full article
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13 pages, 1070 KiB  
Review
Azapeptides as an Efficient Tool to Improve the Activity of Biologically Effective Peptides
by Karima Tarchoun, Mo’ath Yousef and Zoltán Bánóczi
Future Pharmacol. 2022, 2(3), 293-305; https://doi.org/10.3390/futurepharmacol2030020 - 11 Aug 2022
Cited by 6 | Viewed by 1963
Abstract
Peptides are highly potent biological active compounds with excellent selectivity and binding, but they have some drawbacks (e.g., low stability in vivo because of the enzymatic degradation, and fast elimination). To overcome their drawbacks, various peptidomimetics have been gaining ground. Different modifications have [...] Read more.
Peptides are highly potent biological active compounds with excellent selectivity and binding, but they have some drawbacks (e.g., low stability in vivo because of the enzymatic degradation, and fast elimination). To overcome their drawbacks, various peptidomimetics have been gaining ground. Different modifications have been examined, such as the modification of peptide backbone. One such seemingly simple modification is the replacement of the CHα group by an N atom. These amino acid derivatives are called azaamino acids, and peptides containing azaamino acid are called azapeptides. This exchange results in both steric and electronic differences from the original amino acids, thus affecting the structure and biological activity of the modified peptide. In this review, the synthesis possibilities of azapeptides and the impact of azaamino acid incorporation on the structure and biological activity are presented through examples. Different synthetic solutions for azaamino acid introduction and the various routes to build in the side chain are summarized to illustrate the improvement of the field of azaamino acid chemistry. The influence of the altered electronic and steric properties of N-atom on the structure is described, too. Finally, some examples are given with potent biological activity. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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6 pages, 771 KiB  
Communication
Pandemic Preparedness: The Potential Advantage of Medicines That Prevent Acute Side Effects of Vaccination, SARS-CoV-2 as an Example
by Pantea Kiani, Jessica Balikji, Johan Garssen and Joris C. Verster
Future Pharmacol. 2022, 2(3), 287-292; https://doi.org/10.3390/futurepharmacol2030019 - 01 Aug 2022
Cited by 1 | Viewed by 2015
Abstract
Vaccination against SARS-CoV-2 is an important and essential strategy to combat the 2019 coronavirus disease (COVID-19) pandemic. Vaccination has shown to be effective in reducing the spread of SARS-CoV-2, reducing the chances of becoming infected and developing severe COVID-19, and reducing hospitalization and [...] Read more.
Vaccination against SARS-CoV-2 is an important and essential strategy to combat the 2019 coronavirus disease (COVID-19) pandemic. Vaccination has shown to be effective in reducing the spread of SARS-CoV-2, reducing the chances of becoming infected and developing severe COVID-19, and reducing hospitalization and mortality rates. However, the vaccinations against SARS-CoV-2 are accompanied by undesirable side effects which may be in part responsible for a reduction in the willingness to become vaccinated. At this moment (June 2022), 24.3% of the US adult population (18+ years old) is not fully vaccinated against SARS-CoV-2, and 49.5% did not receive their follow-up booster vaccination. The most important motives for refusing vaccination are the unknown long-term side effects and the known acute side effects of vaccination. Here, we discuss the importance of recognizing the impact of this reactogenicity on individuals’ willingness to vaccinate and how the development of effective and safe medicines that prevent or mitigate the unwanted side effects of the vaccination may help to increase the willingness to vaccinate. Full article
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11 pages, 934 KiB  
Review
The Pharmacogenetics of Treatment with Quetiapine
by María Ortega-Ruiz, Paula Soria-Chacartegui, Gonzalo Villapalos-García, Francisco Abad-Santos and Pablo Zubiaur
Future Pharmacol. 2022, 2(3), 276-286; https://doi.org/10.3390/futurepharmacol2030018 - 24 Jul 2022
Cited by 4 | Viewed by 8018
Abstract
Quetiapine is a second-generation antipsychotic used for the treatment of schizophrenia, depression and bipolar disorder. The aim of this traditional review was to summarize the available pharmacogenetic information on this drug and to conclude about its clinical relevance. For this purpose, bibliographic research [...] Read more.
Quetiapine is a second-generation antipsychotic used for the treatment of schizophrenia, depression and bipolar disorder. The aim of this traditional review was to summarize the available pharmacogenetic information on this drug and to conclude about its clinical relevance. For this purpose, bibliographic research was performed in the Pharmacogenomics Knowledge Base (PharmGKB) database. A total of 23 articles were initially retrieved, of which 15 were finally included. A total of 19 associations were observed between 15 genes, such as CYP3A4, CYP3A5, COMT or MC4R, and 29 clinical events. No associations were consistently replicated between pharmacogenetic biomarkers and clinical events, except for that between the CYP3A4 phenotype and quetiapine exposure, which was the only one considered clinically relevant. Consistently, the DPWG published a clinical guideline on this association, where dose adjustments for CYP3A4 poor metabolizers (PMs) are indicated to prevent the occurrence of adverse drug reactions (ADRs). Full article
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20 pages, 1920 KiB  
Review
Promising Therapeutic Strategies Targeting Mitochondria in Kidney Diseases: From Small Molecules to Whole Mitochondria
by Alexis Paulina Jiménez-Uribe and José Pedraza-Chaverri
Future Pharmacol. 2022, 2(3), 256-275; https://doi.org/10.3390/futurepharmacol2030017 - 22 Jul 2022
Viewed by 2298
Abstract
Kidney function highly depends on mitochondria, organelles that regulate different metabolic pathways. Mitochondria-altered function and structure are present during acute kidney injury (AKI) and chronic kidney disease (CKD). Targeting mitochondria using several strategies has been shown to improve kidney function. Here, we review [...] Read more.
Kidney function highly depends on mitochondria, organelles that regulate different metabolic pathways. Mitochondria-altered function and structure are present during acute kidney injury (AKI) and chronic kidney disease (CKD). Targeting mitochondria using several strategies has been shown to improve kidney function. Here, we review some experimental mitochondria targeting strategies with clinical potential in kidney diseases encompassing cationic/lipophilic small molecules, peptides, nanocarriers, and even the entire organelle. Full article
(This article belongs to the Special Issue Mitochondria as Potential Target in Disease Therapy)
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18 pages, 6511 KiB  
Article
Oxostephanine, Thalmiculine, and Thaliphyline—Three Isoquinoleine Alkaloids That Inhibit L-Type Voltage-Gated Ca2+ Channels
by Jacinthe Frangieh, Claire Legendre, Dimitri Bréard, Pascal Richomme, Daniel Henrion, Ziad Fajloun, César Mattei, Anne-Marie Le Ray and Christian Legros
Future Pharmacol. 2022, 2(3), 238-255; https://doi.org/10.3390/futurepharmacol2030016 - 30 Jun 2022
Viewed by 1997
Abstract
The isoquinoline alkaloids (IAs) represent a large and diverse subfamily of phytochemicals in terms of structures and pharmacological activities, including ion channel inhibition. Several IAs, such as liriodenine (an oxoaporphine) and curine (a bisbenzylisoquinoline (BBIQ), inhibit the L-type voltage-gated Ca2+ channels (LTCC). [...] Read more.
The isoquinoline alkaloids (IAs) represent a large and diverse subfamily of phytochemicals in terms of structures and pharmacological activities, including ion channel inhibition. Several IAs, such as liriodenine (an oxoaporphine) and curine (a bisbenzylisoquinoline (BBIQ), inhibit the L-type voltage-gated Ca2+ channels (LTCC). In this study, we aimed to search for new blockers of LTCC, which are therapeutic targets in neurological and cardiovascular diseases. We set up a screening assay using the rat pituitary GH3b6 cell line, which expresses two LTCC isoforms, CaV1.2 and CaV1.3. Both LTCC subtypes can be indirectly activated by KCl concentration elevation or directly by the dihydropyridine (DHP), BAY K8644, leading to an increase in the intracellular Ca2+ concentration ([Ca2+]i). These Ca2+ responses were completely blocked by the selective LTCC DHP inhibitor, nifedipine. Thereby, 16 selected IAs were tested for their ability to inhibit KCl and BAY K8644-induced Ca2+ responses. We then identified three new potent LTCC blockers, namely, oxostephanine, thaliphyline, and thalmiculine. They inhibited LTCC with IC50 values in the micromolar range through interaction to a binding site different to that of dihydropyridines. The two subfamilies of IAs, oxoaporphine with oxostephanine, and BBIQs with both thalyphilline and thalmiculine, constitute interesting pharmacophores for the development of future therapeutic leads for neurological and cardiovascular diseases. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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24 pages, 10327 KiB  
Review
Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System
by Aadil Javed, Gianluca Malagraba, Mahdieh Yarmohammadi, Catalina M. Perelló-Reus, Carles Barceló and Teresa Rubio-Tomás
Future Pharmacol. 2022, 2(3), 214-237; https://doi.org/10.3390/futurepharmacol2030015 - 30 Jun 2022
Cited by 3 | Viewed by 2888
Abstract
Mitosis entails mechanistic changes required for maintaining the genomic integrity in all dividing cells. The process is intricate and temporally and spatially regulated by the ordered series of activation and de-activation of protein kinases. The mitotic kinases ensure the stepwise progression of entry [...] Read more.
Mitosis entails mechanistic changes required for maintaining the genomic integrity in all dividing cells. The process is intricate and temporally and spatially regulated by the ordered series of activation and de-activation of protein kinases. The mitotic kinases ensure the stepwise progression of entry into mitosis after the G2 phase of the cell cycle, followed by prophase, pro-metaphase, metaphase, anaphase, telophase, and subsequently cytokinesis and birth of two daughter cells with equal segregation and distribution of the genome. The major mitotic kinases include cyclin-dependent kinase 1 (CDK1), Aurora A and B Kinases, and Polo-Like-Kinase 1 (PLK1), among others. Overexpression of some of these kinases has been reported in many cancers as the mitotic fidelity and genome integrity are interlinked and dependent on these regulators, the native irregularities in these factors can be targeted as therapeutic strategies for various cancers. Here, we report and summarize the recent updates on the literature describing the various mitotic inhibitors targeting kinases, which can be used as potential therapeutic interventions for gastrointestinal cancers including gastric cancer, liver cancer, pancreatic cancer and colorectal cancer. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology)
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16 pages, 740 KiB  
Review
The Role of Lactic Acid in the Management of Bacterial Vaginosis: A Systematic Literature Review
by Werner Mendling, Maged Atef El Shazly and Lei Zhang
Future Pharmacol. 2022, 2(3), 198-213; https://doi.org/10.3390/futurepharmacol2030014 - 29 Jun 2022
Cited by 4 | Viewed by 12091
Abstract
Bacterial vaginosis (BV) is a common infection characterized by an imbalance in the vaginal microbiome. Alongside the extensive research for effective therapies, treatment recommendations for symptomatic BV with antibiotics have been developed and are currently available. However, the recurrence of BV remains a [...] Read more.
Bacterial vaginosis (BV) is a common infection characterized by an imbalance in the vaginal microbiome. Alongside the extensive research for effective therapies, treatment recommendations for symptomatic BV with antibiotics have been developed and are currently available. However, the recurrence of BV remains a considerable challenge given that about 60% of women experience BV relapse within six months after initial treatment. In addition, clear guidelines on the treatment of asymptomatic BV during pregnancy or for BV mixed infections are still missing. Lactic acid has been put forward as a potential treatment or for prophylaxis of BV due to its ability to restore the imbalance of the vaginal microbiota and to promote the disruption of vaginal pathogenic bacterial biofilms, which might trigger BV recurrence. This review evaluates the clinical evidence regarding the efficacy and prophylactic potential of lactic acid in BV through a systematic literature search. In addition, a treatment regimen consisting of lactic acid as a standalone treatment or in combination with current recommended therapies for practice is suggested based on these findings and stratified according to BV severity, pregnancy status, and coincidence with vulvovaginal candidosis (VVC) or trichomoniasis. Full article
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