Journal Description
Pharmaceuticals
Pharmaceuticals
is a peer-reviewed, open access journal of medicinal chemistry and related drug sciences, published monthly online by MDPI. The Academy of Pharmaceutical Sciences (APS) is partners of Pharmaceuticals and their members receive a discount on the article processing charge.
- Open Access free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Pharmacology & Pharmacy) / CiteScore - Q2 (Pharmaceutical Science)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14.6 days after submission; acceptance to publication is undertaken in 3.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Testimonials: See what our editors and authors say about Pharmaceuticals.
- International Electronic Conference on Medicinal Chemistry (https://sciforum.net/series/ecmc/latest)
- Companion journals for Pharmaceuticals include: Pharmacoepidemiology, Psychoactives and Drugs and Drug Candidates.
Impact Factor:
4.6 (2022);
5-Year Impact Factor:
4.9 (2022)
Latest Articles
Evaluation of Serial Procalcitonin Levels for the Optimization of Antibiotic Use in Non-Critically Ill COVID-19 Patients
Pharmaceuticals 2024, 17(5), 624; https://doi.org/10.3390/ph17050624 (registering DOI) - 12 May 2024
Abstract
Background: Procalcitonin (PCT) has been used as a biomarker to guide antibiotic therapy in various patient populations. However, its role in optimizing antibiotic use in COVID-19 patients has not been well studied to date. Thus, we aimed to evaluate the use of serial
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Background: Procalcitonin (PCT) has been used as a biomarker to guide antibiotic therapy in various patient populations. However, its role in optimizing antibiotic use in COVID-19 patients has not been well studied to date. Thus, we aimed to evaluate the use of serial PCT monitoring as an antimicrobial stewardship tool for COVID-19 patients. Methods: This retrospective study included 240 COVID-19 patients who were admitted to a tertiary medical institution in Saudi Arabia between January 2020 and February 2022. Patients who received empiric antibiotic therapy for community-acquired pneumonia (CAP) and had serial procalcitonin levels were included. The patients were divided into two groups: the normal procalcitonin arm (PCT level < 0.5 ng/mL) and the elevated PCT arm (PCT level > 0.5 ng/mL). The primary and secondary outcomes were the effect of PCT monitoring on the duration of antibiotic exposure and the length of hospital stay, respectively. To measure the accuracy of PCT, the receiver-operating characteristic area under the curve (ROC-AUC) was determined. Results: Among the included patients, 142 were in the normal procalcitonin arm (median PCT, 0.12 ng/mL), and 78 were in the elevated PCT arm (median PCT, 4.04 ng/mL). The baseline characteristics were similar between the two arms, except for the higher prevalence of kidney disease in the elevated PCT arm. There was no statistically significant difference in the duration of antibiotic exposure between the normal and elevated PCT arms (median duration: 7 days in both arms). However, the length of hospital stay was significantly shorter in the normal PCT arm (median stay, 9 days) than in the elevated PCT arm (median stay, 13 days; p = 0.028). The ROC-AUC value was 0.54 (95% CI: 0.503–0.595). Conclusions: Serial PCT monitoring did not lead to a reduction in the duration of antibiotic exposure in COVID-19 patients. However, it was associated with a shorter hospital stay. These findings suggest that PCT monitoring may be useful for optimizing antibiotic use and improving outcomes in COVID-19 patients. While PCT-guided algorithms have the potential to enable antibiotic stewardship, their role in the context of COVID-19 treatment requires further investigation.
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(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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Molecular Mechanisms and Therapeutic Potential of Gabapentin with a Focus on Topical Formulations to Treat Ocular Surface Diseases
by
Dario Rusciano
Pharmaceuticals 2024, 17(5), 623; https://doi.org/10.3390/ph17050623 (registering DOI) - 11 May 2024
Abstract
Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to
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Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases.
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(This article belongs to the Special Issue Ophthalmic Pharmacology)
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Bipolar Radiofrequency and Non-Crosslinked Hyaluronic Acid Plus Calcium Hydroxyapatite in the Treatment of Stress Urinary Incontinence
by
Piotr Kolczewski, Mariusz Łukaszuk, Aneta Cymbaluk-Płoska, Mateusz Kozłowski, Sylwester Ciećwież, Rafał Kuźlik and Nicola Zerbinati
Pharmaceuticals 2024, 17(5), 622; https://doi.org/10.3390/ph17050622 (registering DOI) - 11 May 2024
Abstract
Background: Stress urinary incontinence (SUI) causes both physical and psychological problems to women and their partners. Recently, vaginal radiofrequency (RF) application, as well as the administration of non-crosslinked hyaluronic acid (NCLHA) together with calcium hydroxyapatite (CaHA), has attracted attention for SUI treatment. The
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Background: Stress urinary incontinence (SUI) causes both physical and psychological problems to women and their partners. Recently, vaginal radiofrequency (RF) application, as well as the administration of non-crosslinked hyaluronic acid (NCLHA) together with calcium hydroxyapatite (CaHA), has attracted attention for SUI treatment. The current, comparative study evaluated the efficacy and safety of these technologies acting separately and in a combined treatment. Methods: Sixty women with mild to moderate SUI, aged between 46 and 76 years (mean age 63.2) were divided into three groups intended for different treatments: group I, RF vaginal treatment only, group II, NCLHA plus CaHA periurethral injection only, group III, combined treatment including a single periurethral injection of NCLHA plus CaHA followed by four vaginal applications of RF at intervals of 3–5 days. The clinical effects of the treatments were evaluated by ICIQ-LUTSqol (Polish version) and UDI-6. Results: The obtained results suggest that the symptoms of SUI and the quality of life of the patients improved significantly in each group after the therapies compared to the pre-treatment levels and were more persistent in the third HA + RF group compared to the HA or the RF group.
Full article
(This article belongs to the Special Issue Hydrogels for Pharmaceutical and Biomedical Applications 2024)
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Synthesis and Evaluation of Novel 68Ga-Labeled [D-Phe6,Leu13ψThz14]bombesin(6-14) Analogs for Cancer Imaging with Positron Emission Tomography
by
Lei Wang, Chao-Cheng Chen, Zhengxing Zhang, Hsiou-Ting Kuo, Chengcheng Zhang, Nadine Colpo, Helen Merkens, François Bénard and Kuo-Shyan Lin
Pharmaceuticals 2024, 17(5), 621; https://doi.org/10.3390/ph17050621 (registering DOI) - 11 May 2024
Abstract
Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a
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Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [68Ga]Ga-TacsBOMB2 ([68Ga]Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13ψThz14-NH2), which showed a minimal pancreas uptake in a preclinical mouse model. In this study, we synthesized four derivatives with unnatural amino acid substitutions (Tle10-derived Ga-LW01158, NMe-His12-derived Ga-LW01160, α-Me-Trp8- and Tle10-derived Ga-LW01186, and Tle10- and N-Me-Gly11-derived Ga-LW02002) and evaluated their potential for detecting GRPR-expressing tumors with positron emission tomography (PET). The binding affinities (Ki(GRPR)) of Ga-LW01158, Ga-LW01160, Ga-LW01186, and Ga-LW02002 were 5.11 ± 0.47, 187 ± 17.8, 6.94 ± 0.95, and 11.0 ± 0.39 nM, respectively. [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 enabled clear visualization of subcutaneously implanted human prostate cancer PC-3 tumor xenografts in mice in PET images. Ex vivo biodistribution studies showed that [68Ga]Ga-LW01158 had the highest tumor uptake (11.2 ± 0.65 %ID/g) and good tumor-to-background uptake ratios at 1 h post-injection. Comparable in vivo stabilities were observed for [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 (76.5–80.7% remaining intact in mouse plasma at 15 min post-injection). In summary, the Tle10 substitution, either alone or combined with α-Me-Trp8 or NMe-Gly11 substitution, in Ga-TacsBOMB2 generates derivatives that retained good GRPR binding affinity and in vivo stability. With good tumor uptake and tumor-to-background imaging contrast, [68Ga]Ga-LW01158 is promising for detecting GRPR-expressing lesions with PET.
Full article
(This article belongs to the Special Issue Development of Radiolabeled Peptides)
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The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods
by
Antonio Curcio, Roberta Rocca, Stefano Alcaro and Anna Artese
Pharmaceuticals 2024, 17(5), 620; https://doi.org/10.3390/ph17050620 (registering DOI) - 10 May 2024
Abstract
Histone deacetylases (HDACs) are crucial in gene transcription, removing acetyl groups from histones. They also influence the deacetylation of non-histone proteins, contributing to the regulation of various biological processes. Thus, HDACs play pivotal roles in various diseases, including cancer, neurodegenerative disorders, and inflammatory
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Histone deacetylases (HDACs) are crucial in gene transcription, removing acetyl groups from histones. They also influence the deacetylation of non-histone proteins, contributing to the regulation of various biological processes. Thus, HDACs play pivotal roles in various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions, highlighting their potential as therapeutic targets. This paper reviews the structure and function of the four classes of human HDACs. While four HDAC inhibitors are currently available for treating hematological malignancies, numerous others are undergoing clinical trials. However, their non-selective toxicity necessitates ongoing research into safer and more efficient class-selective or isoform-selective inhibitors. Computational methods have aided the discovery of HDAC inhibitors with the desired potency and/or selectivity. These methods include ligand-based approaches, such as scaffold hopping, pharmacophore modeling, three-dimensional quantitative structure–activity relationships, and structure-based virtual screening (molecular docking). Moreover, recent developments in the field of molecular dynamics simulations, combined with Poisson–Boltzmann/molecular mechanics generalized Born surface area techniques, have improved the prediction of ligand binding affinity. In this review, we delve into the ways in which these methods have contributed to designing and identifying HDAC inhibitors.
Full article
(This article belongs to the Special Issue Selective Histone Deacetylase Isoforms as Potential Therapeutic Targets)
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Protective Effects of Dietary Vitamin D3, Turmeric Powder, and Their Combination against Gasoline Intoxication in Rats
by
Gulfira A. Yestemirova, Zura B. Yessimsiitova and Michael Danilenko
Pharmaceuticals 2024, 17(5), 619; https://doi.org/10.3390/ph17050619 (registering DOI) - 10 May 2024
Abstract
The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful
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The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be important and timely issues. In this study, we investigated the potential of vitamin D3, turmeric powder, and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without the supplementation of vitamin D3 (750 IU/kg body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5 ± 1.3 cm3/h/m3/day) for 30, 60, or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While the exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D3, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, the destruction of the lobular structure and hepatocytolysis in the liver, the shrinkage and fragmentation of glomeruli in the kidneys, and the disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D3, noticeably alleviated the above conditions. This was accompanied by a significant improvement in the blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D3. The fact that the protective activity of vitamin D3 alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately.
Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Natural Products)
Open AccessArticle
Elderberry Leaves with Antioxidant and Anti-Inflammatory Properties as a Valuable Plant Material for Wound Healing
by
Elżbieta Studzińska-Sroka, Magdalena Paczkowska-Walendowska, Zuzanna Woźna, Tomasz Plech, Piotr Szulc and Judyta Cielecka-Piontek
Pharmaceuticals 2024, 17(5), 618; https://doi.org/10.3390/ph17050618 (registering DOI) - 10 May 2024
Abstract
Sambuci folium (elderberry leaves) have been used in traditional medicine, mainly externally, to treat skin diseases and wounds. Therefore, the aim of this study was to screen the biological activity of elderberry leaves (antioxidant potential and possibility of inhibition of tyrosinase and hyaluronidase
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Sambuci folium (elderberry leaves) have been used in traditional medicine, mainly externally, to treat skin diseases and wounds. Therefore, the aim of this study was to screen the biological activity of elderberry leaves (antioxidant potential and possibility of inhibition of tyrosinase and hyaluronidase enzymes) combined with phytochemical analysis. For this purpose, a phytochemical analysis was carried out. Elderberry leaves of 12 varieties (“Sampo”, “Obelisk”, “Dwubarwny”, “Haschberg”, “Haschberg 1”, “Koralowy”, “Sambo”, “Black Beauty”, “Black Tower”, “Golden hybrid”, “Samyl”, “Samyl 1”) in two growth stages. The compounds from the selected groups, phenolic acids (chlorogenic acid) and flavonols (quercetin), were chromatographically determined in hydroalcoholic leaf extracts. All tested elderberry leaf extracts showed antioxidant effects, but the most promising potential: very high compounds content (TPC = 61.85 mg GAE/g), antioxidant (e.g., DPPH IC50 = 1.88 mg/mL; CUPRAC IC0.5 = 0.63 mg/mL) and optimal anti-inflammatory (inhibition of hyaluronidase activity 41.28%) activities were indicated for older leaves of the “Sampo” variety. Additionally, the extract obtained from “Sampo” and “Golden hybrid” variety facilitated the treatment of wounds in the scratch test. In summary, the best multidirectional pro-health effect in treating skin inflammation was specified for “Sampo” leaves II extract (leaves during the flowering period); however, wound treatment was noted as rich in chlorogenic acid younger leaf extracts of the “Golden hybrid” variety.
Full article
(This article belongs to the Special Issue Phytochemicals and Analogues as Sources of Bioactive Substances of Pharmacological and Industrial Interest)
Open AccessArticle
Network Pharmacology and Experimental Validation to Explore the Potential Mechanism of Nigella sativa for the Treatment of Breast Cancer
by
Rawaba Arif, Shazia Anwer Bukhari, Ghulam Mustafa, Sibtain Ahmed and Mohammed Fahad Albeshr
Pharmaceuticals 2024, 17(5), 617; https://doi.org/10.3390/ph17050617 (registering DOI) - 10 May 2024
Abstract
Breast cancer is a prevalent and potentially life-threatening disease that affects women worldwide. Natural products have gained attention as potential anticancer agents due to their fewer side effects, low toxicity, and cost effectiveness compared to traditional chemotherapy drugs. In the current study, the
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Breast cancer is a prevalent and potentially life-threatening disease that affects women worldwide. Natural products have gained attention as potential anticancer agents due to their fewer side effects, low toxicity, and cost effectiveness compared to traditional chemotherapy drugs. In the current study, the network pharmacology approach was used following a molecular docking study to evaluate the therapeutic potential of N. sativa-derived phytochemicals against breast cancer. Specifically, the study aimed to identify potential anticancer agents targeting key proteins implicated in breast cancer progression. Five proteins (i.e., EGFR, MAPK3, ESR1, MAPK1, and PTGS2) associated with breast cancer were selected as receptor proteins. Fourteen phytochemicals from N. sativa were prioritized based on drug-likeness (DL) and oral bioavailability (OB) parameters (with criteria set at DL > 0.18 and OB > 30%, respectively). Subsequent analysis of gene targets identified 283 overlapping genes primarily related to breast cancer pathogenesis. Ten hub genes were identified through topological analysis based on their significance in the KEGG pathway and GO annotations. Molecular docking revealed strong binding affinities between folic acid, betulinic acid, stigmasterol, and selected receptor proteins. These phytochemicals also demonstrated druggability potential. In vitro experiments in the MDA-MB-231 breast cancer cell line revealed that betulinic acid and stigmasterol significantly reduced cell viability after 24 h of treatment, confirming their anticancer activity. Furthermore, in vivo evaluation using a DMBA-induced rat model showed that betulinic acid and stigmasterol contributed to the significant recovery of cancer markers. This study aimed to explore the mechanisms underlying the anticancer potential of N. sativa phytochemicals against breast cancer, with the ultimate goal of identifying novel therapeutic candidates for future drug development. Overall, these results highlight betulinic acid and stigmasterol as promising candidates to develop novel anticancer agents against breast cancer. The comprehensive approach of this study, which integrates network pharmacology and molecular docking study and its experimental validation, strengthens the evidence supporting the therapeutic benefits of N. sativa-derived phytochemicals in breast cancer treatment, making them promising candidates for the development of novel anticancer agents against breast cancer.
Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Drug Discovery)
Open AccessReview
Anti-Emetics in Children Receiving Chemotherapy for Solid Tumors and Leukemia: Pharmacology and Optimization of Therapy for Nausea and Vomiting
by
Shuvadeep Ganguly, Archana Sasi, Santhosh Kumar Kodagalli Nagaraju and Sameer Bakhshi
Pharmaceuticals 2024, 17(5), 616; https://doi.org/10.3390/ph17050616 (registering DOI) - 10 May 2024
Abstract
The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used
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The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m2/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1–3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription.
Full article
(This article belongs to the Special Issue Pharmacology of Pediatric Medicines)
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Substance Addiction Rehabilitation Drugs
by
Shu Yuan, Si-Cong Jiang, Zhong-Wei Zhang, Zi-Lin Li and Jing Hu
Pharmaceuticals 2024, 17(5), 615; https://doi.org/10.3390/ph17050615 - 10 May 2024
Abstract
The relapse rate of substance abusers is high, and addiction rehabilitation adjunct drugs need to be developed urgently. There have been numerous reports on blocking the formation of substance addiction, but studies on drugs that can alleviate withdrawal symptoms are very limited. Both
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The relapse rate of substance abusers is high, and addiction rehabilitation adjunct drugs need to be developed urgently. There have been numerous reports on blocking the formation of substance addiction, but studies on drugs that can alleviate withdrawal symptoms are very limited. Both the dopamine transporter (DAT) hypothesis and D3 dopamine receptor (D3R) hypothesis are proposed. DAT activators reduce the extracellular dopamine level, and D3R antagonists reduce the neuron’s sensitivity to dopamine, both of which may exacerbate the withdrawal symptoms subsequently. The D3R partial agonist SK608 has biased signaling properties via the G-protein-dependent pathway but did not induce D3R desensitization and, thus, may be a promising drug for the withdrawal symptoms. Drugs for serotoninergic neurons or GABAergic neurons and anti-inflammatory drugs may have auxiliary effects to addiction treatments. Drugs that promote structural synaptic plasticity are also discussed.
Full article
(This article belongs to the Special Issue Advances in Neuropharmacology of Drug Abuse)
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Comprehensive Chemical Profiling and Mechanistic Insight into Anticancer Activity of Annona muricata Leaves Extract
by
Rehab H. Abdallah, Al-sayed R. Al-Attar, Youssef M. Shehata, Doaa M. Abdel-Fattah, Rahnaa M. Atta, Omer I. Fantoukh and Ahmed M. Mustafa
Pharmaceuticals 2024, 17(5), 614; https://doi.org/10.3390/ph17050614 - 10 May 2024
Abstract
The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract’s impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity
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The aqueous extract of Annona muricata L. leaves was thoroughly analyzed using the UPLC-MS/MS, in addition to a new approach of examination of the extract’s impact on cancer of EAC(Ehrlich ascites carcinoma) in albino male mice. The aim was to investigate the diversity of the phytochemical constituents of the aqueous leaf capsule extract and their impacts on EAC as anticancer agents. The UPLC-ESI-MS/MS screening resulted in 410 tentatively identified metabolites. Among them, 384 compounds were tentatively identified in a previous study, besides a number of 26 compounds belonging to acetogenins, phenolics, flavonoids, alkaloids, and other miscellaneous compounds, which were exclusively identified in the aqueous extract of the leaf capsule. Interestingly, a new compound was tentatively characterized as galloyl-quinic acid-rutinoside. This study also demonstrated that treating EAC mice with an extract from A. muricata leaves significantly improved the abnormalities in the expression of pro-apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) genes. Furthermore, the extract showed good protection against induced Ehrlich hepatocarcinoma, according to the microscopical, histological, and immune-histochemical analyses of the liver tissues and tumor mass.
Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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Drug–Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain
by
Maria G. Campos, Maria China, Mariana Cláudio, Miguel Capinha, Rita Torres, Simão Oliveira and Ana Fortuna
Pharmaceuticals 2024, 17(5), 613; https://doi.org/10.3390/ph17050613 - 10 May 2024
Abstract
Clinical practice entails a translation of research that assists in the use of scientific data and therapeutic evidence for the benefit of the patient. This review critically summarizes the potential impact of cannabinoids in conjunction with other drugs when associated with treatments for
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Clinical practice entails a translation of research that assists in the use of scientific data and therapeutic evidence for the benefit of the patient. This review critically summarizes the potential impact of cannabinoids in conjunction with other drugs when associated with treatments for epilepsy, autism spectrum disorder, cancer, multiple sclerosis, and chronic pain. In these associations, potential drug interactions may occur and alter the predicted clinical results. Therefore, the potential for drug interactions must always be assessed to avoid therapeutic failures and/or increased side effects. Some effects may be additive, synergistic, or antagonistic, but changes in absorption, distribution, metabolism, particularly through cytochrome P450 (CYP) isoenzymes (e.g., CYP2C9 and CYP3A4), and excretion may also occur. For example, the combination of cannabis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases the plasma concentration of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In contrast, rifampicin, a CYP3A4 inducer, stands out for reducing plasma THC levels by approximately 20–40% and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Pharmacokinetic interactions with anticonvulsant medications have also been reported, as have pharmacodynamic interactions between cannabinoids and medications with sympathomimetic effects (e.g., tachycardia, hypertension), central nervous system depressants (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia and somnolence). Although further studies are still pending, there is currently clinical evidence supporting drug interactions with cannabinoids, requiring doctors to evaluate the risk of drug combinations with cannabinoids and vice versa. The tables provided here were designed to facilitate the identification of biorelevant interactions that may compromise therapeutic efficacy and toxicity.
Full article
(This article belongs to the Special Issue Therapeutic Potential of Cannabinoid Receptors Type 1 and 2—Novel Insights for Enhancing the Chance of Clinical Success)
Open AccessReview
Blood–Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience
by
Evridiki Asimakidou, Justin Kok Soon Tan, Jialiu Zeng and Chih Hung Lo
Pharmaceuticals 2024, 17(5), 612; https://doi.org/10.3390/ph17050612 - 10 May 2024
Abstract
Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to the brain. While the BBB serves as a crucial protective barrier, it poses challenges in delivering therapeutic agents to their intended targets within the brain parenchyma. To enhance drug
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Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to the brain. While the BBB serves as a crucial protective barrier, it poses challenges in delivering therapeutic agents to their intended targets within the brain parenchyma. To enhance drug delivery for the treatment of neurological diseases, several delivery technologies to circumvent the BBB have been developed in the last few years. Among them, nanoparticles (NPs) are one of the most versatile and promising tools. Here, we summarize the characteristics of NPs that facilitate BBB penetration, including their size, shape, chemical composition, surface charge, and importantly, their conjugation with various biological or synthetic molecules such as glucose, transferrin, insulin, polyethylene glycol, peptides, and aptamers. Additionally, we discuss the coating of NPs with surfactants. A comprehensive overview of the common in vitro and in vivo models of the BBB for NP penetration studies is also provided. The discussion extends to discussing BBB impairment under pathological conditions and leveraging BBB alterations under pathological conditions to enhance drug delivery. Emphasizing the need for future studies to uncover the inherent therapeutic properties of NPs, the review advocates for their role beyond delivery systems and calls for efforts translating NPs to the clinic as therapeutics. Overall, NPs stand out as a highly promising therapeutic strategy for precise BBB targeting and drug delivery in neurological disorders.
Full article
(This article belongs to the Special Issue Protein-Based Biosensors and Biomaterials for Diagnostic Application and Drug Discovery)
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Open AccessArticle
Torenia sp. Extracts Contain Multiple Potent Antitumor Compounds with Nematocidal Activity, Triggering an Activated DNA Damage Checkpoint and Defective Meiotic Progression
by
Qinghao Meng, Robert P. Borris and Hyun-Min Kim
Pharmaceuticals 2024, 17(5), 611; https://doi.org/10.3390/ph17050611 - 10 May 2024
Abstract
Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in Caenorhabditis elegans. In this study, our attention was directed towards Torenia sp., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and
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Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in Caenorhabditis elegans. In this study, our attention was directed towards Torenia sp., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and disrupted meiotic progression, thus disrupting developmental processes. Notably, Torenia sp. extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, hindering germline development. LC–MS analysis revealed 13 compounds in the Torenia sp. extracts, including flavonoids, terpenoids, tanshinones, an analog of resveratrol, iridoids, carotenoids, fatty acids, and alkaloids. Of these, 10 are known for their antitumor activity, suggesting the potential of Torenia species beyond traditional gardening, extending into pharmaceutical and therapeutic applications.
Full article
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants — In Honour of the 20th Anniversary of Pharmaceuticals)
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Open AccessSystematic Review
The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis—The Case of the Xanomeline–Trospium Combination: A Systematic Review
by
Octavian Vasiliu, Beatrice Budeanu and Mihai-Ștefan Cătănescu
Pharmaceuticals 2024, 17(5), 610; https://doi.org/10.3390/ph17050610 - 9 May 2024
Abstract
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline–trospium (KarXT) is a
[...] Read more.
Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline–trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline–trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.
Full article
(This article belongs to the Special Issue Recent Advances in Drug Discovery and Evaluation for the Treatment of Affective Disorders and Schizophrenia)
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Open AccessArticle
Evaluation of The Effect of Loratadine versus Diosmin/Hesperidin Combination on Vinca Alkaloids-Induced Neuropathy: A Randomized Controlled Clinical Trial
by
Noha Kamal, Mahmoud S. Abdallah, Essam Abdel Wahed, Nagwa A. Sabri and Sarah Farid Fahmy
Pharmaceuticals 2024, 17(5), 609; https://doi.org/10.3390/ph17050609 - 9 May 2024
Abstract
Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients
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Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group–neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.
Full article
(This article belongs to the Special Issue Cancer Treatment Toxicities: Molecular Insights and Novel Therapeutic Approaches)
Open AccessArticle
Synthesis, Activity, Toxicity, and In Silico Studies of New Antimycobacterial N-Alkyl Nitrobenzamides
by
João P. Pais, Olha Antoniuk, David Pires, Tiago Delgado, Andreia Fortuna, Paulo J. Costa, Elsa Anes and Luis Constantino
Pharmaceuticals 2024, 17(5), 608; https://doi.org/10.3390/ph17050608 - 9 May 2024
Abstract
Tuberculosis (TB) is a disease that plagues the frailest members of society. We have developed a family of N-alkyl nitrobenzamides that exhibit promising antitubercular activities and can be considered a structural simplification of known inhibitors of decaprenylphosphoryl-β-D-ribofuranose 2′-oxidase (DprE1), an essential Mycobacterium
[...] Read more.
Tuberculosis (TB) is a disease that plagues the frailest members of society. We have developed a family of N-alkyl nitrobenzamides that exhibit promising antitubercular activities and can be considered a structural simplification of known inhibitors of decaprenylphosphoryl-β-D-ribofuranose 2′-oxidase (DprE1), an essential Mycobacterium tuberculosis (Mtb) enzyme and an emergent antitubercular target. Hereby, we report the development of these compounds via a simple synthetic methodology as well as their stability, cytotoxicity, and antitubercular activity. Studying their in vitro activity revealed that the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives were the most active, and within these, the derivatives with intermediate lipophilicities presented the best activities (MIC of 16 ng/mL). Additionally, in an ex vivo macrophage model of infection, the derivatives with chain lengths of six and twelve carbon atoms presented the best results, exhibiting activity profiles comparable to isoniazid. Although the proof is not definite, the assessment of susceptibility over multiple mycobacterial species, together with the structure similarities with known inhibitors of this enzyme, support DprE1 as a likely target of action for the compounds. This idea is also reinforced by the docking studies, where the fit of our more active compounds to the DprE1 binding pocket is very similar to what was observed for known inhibitors like DNB1.
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(This article belongs to the Section Medicinal Chemistry)
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Open AccessReview
Therapeutic Prospects of Mesenchymal Stem Cell and Their Derived Exosomes in the Regulation of the Gut Microbiota in Inflammatory Bowel Disease
by
Yaru Qiao, Xiaohua Tang, Ziyue Liu, Dickson Kofi Wiredu Ocansey, Mengjiao Zhou, Anquan Shang and Fei Mao
Pharmaceuticals 2024, 17(5), 607; https://doi.org/10.3390/ph17050607 - 9 May 2024
Abstract
Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently
[...] Read more.
Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently no long-term effective treatment. As an emerging therapy, MSC-Exs have proven to be effective in alleviating IBD experimentally, and the specific mechanism continues to be explored. The gut microbiota plays an important role in the occurrence and development of IBD, and MSCs and MSC-Exs can effectively regulate gut microbiota in animal models of IBD, but the mechanism involved and whether the outcome can relieve the characteristic dysbiosis necessary to alleviate IBD still needs to be studied. This review provides current evidence on the effective modulation of the gut microbiota by MSC-Exs, offering a basis for further research on the pathogenic mechanism of IBD and MSC-Ex treatments through the improvement of gut microbiota.
Full article
(This article belongs to the Special Issue Stem Cells and Organoids as Tools for Drug Development)
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Open AccessArticle
Arylamines QSAR-Based Design and Molecular Dynamics of New Phenylthiophene and Benzimidazole Derivatives with Affinity for the C111, Y268, and H73 Sites of SARS-CoV-2 PLpro Enzyme
by
Gianfranco Sabadini, Marco Mellado, César Morales and Jaime Mella
Pharmaceuticals 2024, 17(5), 606; https://doi.org/10.3390/ph17050606 - 9 May 2024
Abstract
A non-structural SARS-CoV-2 protein, PLpro, is involved in post-translational modifications in cells, allowing the evasion of antiviral immune response mechanisms. In this study, potential PLpro inhibitory drugs were designed using QSAR, molecular docking, and molecular dynamics. A combined QSAR equation with physicochemical and
[...] Read more.
A non-structural SARS-CoV-2 protein, PLpro, is involved in post-translational modifications in cells, allowing the evasion of antiviral immune response mechanisms. In this study, potential PLpro inhibitory drugs were designed using QSAR, molecular docking, and molecular dynamics. A combined QSAR equation with physicochemical and Free-Wilson descriptors was formulated. The r2, q2, and r2test values were 0.833, 0.770, and 0.721, respectively. From the equation, it was found that the presence of an aromatic ring and a basic nitrogen atom is crucial for obtaining good antiviral activity. Then, a series of structures for the binding sites of C111, Y268, and H73 of PLpro were created. The best compounds were found to exhibit pIC50 values of 9.124 and docking scoring values of −14 kcal/mol. The stability of the compounds in the cavities was confirmed by molecular dynamics studies. A high number of stable contacts and good interactions over time were exhibited by the aryl-thiophenes Pred14 and Pred15, making them potential antiviral candidates.
Full article
(This article belongs to the Section Medicinal Chemistry)
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Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia
by
Leticia Lorena Hernández González, Laura Pérez-Campos Mayoral, María Teresa Hernández-Huerta, Gabriel Mayoral Andrade, Margarito Martínez Cruz, Edgar Ramos-Martínez, Eduardo Pérez-Campos Mayoral, Víctor Cruz Hernández, Ismael Antonio García, Carlos Alberto Matias-Cervantes, Miriam Emily Avendaño Villegas, Carlos Mauricio Lastre Domínguez, Carlos Romero Díaz, Juan de Dios Ruiz-Rosado and Eduardo Pérez-Campos
Pharmaceuticals 2024, 17(5), 605; https://doi.org/10.3390/ph17050605 - 9 May 2024
Abstract
Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by
[...] Read more.
Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κβ inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.
Full article
(This article belongs to the Section Pharmacology)
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