10th Anniversary of Biomedicines—Advances in New Pharmacological Therapies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 41039

Special Issue Editor

Special Issue Information

Dear Colleagues,

The year 2023 marks the 10th anniversary of Biomedicines, a peer-reviewed open access journal in the biomedical field. So far, Biomedicines has published more than 2700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we are publishing a Special Issue entitled 10th Anniversary of Biomedicines—Advances in new pharmacological therapies.  Drugs are bioactive compounds that were originally discovered in the chemical structures that are present in both the plant and animal kingdoms. Both organic and inorganic compounds have been used empirically to cure diseases or to treat the symptoms that are derived from them. Much of modern pharmacology has its origins in these types of compounds. Due to advancements in chemistry, we are able to characterize the chemical composition of any compound with a high degree of accuracy. In fact, we are continuing to discover new compounds in nature that demonstrate very promising pharmacological activities, which could lay the foundation for new, more efficient, and more effective bioactive molecules through chemical modifications. Furthermore, pharmacology is advancing, as new synthetic compounds with increasingly specific and effective pharmacological properties are being developed at a rapid pace. Therefore, in this Special Issue, we plan to collect the latest advances in new drugs of either natural or synthetic origin in addition to describing their biological targets, their specific mechanisms of action, and their effective dosages.

Prof. Dr. Juan Gambini
Guest Editor

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Published Papers (12 papers)

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Research

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11 pages, 1221 KiB  
Article
Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience
by Stefano Levra, Giuseppe Guida, Andrea Elio Sprio, Flavio Crosa, Paolo Carlo Ghio, Francesca Bertolini, Vitina Carriero, Carlo Albera and Fabio Luigi Massimo Ricciardolo
Biomedicines 2022, 10(12), 3229; https://doi.org/10.3390/biomedicines10123229 - 12 Dec 2022
Cited by 5 | Viewed by 2041
Abstract
Pirfenidone and nintedanib are the only two drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF). Both proved to be safe and well-tolerated in clinical trials, but real-world data and direct comparisons are scarce. This real-life study explored the safety profile of [...] Read more.
Pirfenidone and nintedanib are the only two drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF). Both proved to be safe and well-tolerated in clinical trials, but real-world data and direct comparisons are scarce. This real-life study explored the safety profile of pirfenidone and nintedanib with a prolonged follow-up. We retrospectively collected clinical status, adverse events (AEs), and treatment changes from IPF patients who had started an antifibrotic treatment at our centre from December 2011 to December 2020, including 192 patients treated with pirfenidone and 89 with nintedanib. The majority of patients in both groups experienced one or more AEs during the follow-up. A higher proportion of AEs in the nintedanib group were effectively treated with behavioural modifications or additional medications compared with the pirfenidone group (52.5% vs. 40.6%, p = 0.04). Overall, a difference in the impact of AEs due to nintedanib versus pirfenidone resulted in a lower permanent discontinuation of therapy (8.3% vs. 18.3%, p = 0.02), with the latter being associated with a higher risk of drug discontinuation at 48 months after initiation (OR = 2.52, p = 0.03). Our study confirms the safety profile of antifibrotic drugs in IPF but highlights that AEs due to nintedanib are usually easier to manage and lead to fewer cases of permanent discontinuation of therapy. Full article
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12 pages, 284 KiB  
Article
Individualization of Mycophenolic Acid Therapy through Pharmacogenetic, Pharmacokinetic and Pharmacodynamic Testing
by Wolfgang Winnicki, Andreas Fichtenbaum, Goran Mitulovič, Harald Herkner, Florina Regele, Michael Baier, Sieglinde Zelzer, Ludwig Wagner and Guerkan Sengoelge
Biomedicines 2022, 10(11), 2882; https://doi.org/10.3390/biomedicines10112882 - 10 Nov 2022
Cited by 5 | Viewed by 1604
Abstract
Mycophenolic acid (MPA) is a widely used immunosuppressive agent and exerts its effect by inhibiting inosine 5′-monophosphate dehydrogenase (IMPDH), the main regulating enzyme of purine metabolism. However, significant unexplained differences in the efficacy and tolerability of MPA therapy pose a clinical challenge. Therefore, [...] Read more.
Mycophenolic acid (MPA) is a widely used immunosuppressive agent and exerts its effect by inhibiting inosine 5′-monophosphate dehydrogenase (IMPDH), the main regulating enzyme of purine metabolism. However, significant unexplained differences in the efficacy and tolerability of MPA therapy pose a clinical challenge. Therefore, broad pharmacogenetic, pharmacokinetic, and pharmacodynamic approaches are needed to individualize MPA therapy. In this prospective cohort study including 277 renal transplant recipients, IMPDH2 rs11706052 SNP status was assessed by genetic sequencing, and plasma MPA trough levels were determined by HPLC and IMPDH enzyme activity in peripheral blood mononuclear cells (PBMCs) by liquid chromatography–mass spectrometry. Among the 277 patients, 84 were identified with episodes of biopsy-proven rejection (BPR). No association was found between rs11706052 SNP status and graft rejection (OR 1.808, and 95% CI, 0.939 to 3.479; p = 0.076). Furthermore, there was no association between MPA plasma levels and BPR (p = 0.69). However, the patients with graft rejection had a significantly higher predose IMPDH activity in PBMCs compared to the controls without rejection at the time of biopsy (110.1 ± 50.2 vs. 95.2 ± 45.4 pmol/h; p = 0.001), and relative to the baseline IMPDH activity before transplantation (p = 0.042). Our results suggest that individualization of MPA therapy, particularly through pharmacodynamic monitoring of IMPDH activity in PBMCs, has the potential to improve the clinical outcomes of transplant patients. Full article
17 pages, 2851 KiB  
Article
Enhancing Erythropoiesis by a Phytoestrogen Diarylheptanoid from Curcuma comosa
by Kanit Bhukhai, Guillemette Fouquet, Yutthana Rittavee, Nopmullee Tanhuad, Chaiyaporn Lakmuang, Suparerk Borwornpinyo, Usanarat Anurathapan, Apichart Suksamrarn, Pawinee Piyachaturawat, Arthit Chairoungdua, Olivier Hermine and Suradej Hongeng
Biomedicines 2022, 10(6), 1427; https://doi.org/10.3390/biomedicines10061427 - 16 Jun 2022
Cited by 1 | Viewed by 2179
Abstract
Erythropoietin (Epo) is widely used for the treatment of anemia; however, non-hematopoietic effects and cancer risk limit its clinical applications. Therefore, alternative molecules to improve erythropoiesis in anemia patients are urgently needed. Here, we investigated the potential effects of a phytoestrogen diarylheptanoid (3 [...] Read more.
Erythropoietin (Epo) is widely used for the treatment of anemia; however, non-hematopoietic effects and cancer risk limit its clinical applications. Therefore, alternative molecules to improve erythropoiesis in anemia patients are urgently needed. Here, we investigated the potential effects of a phytoestrogen diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, (ASPP 049) isolated from Curcuma comosa on promoting erythropoiesis. Treatment with C. comosa extract improved anemia symptoms demonstrated by increasing red blood cell numbers, hematocrit, and hemoglobin content in anemic mice. In addition, ASPP 049, the major compound isolated from C. comosa, enhanced the suboptimal Epo dosages to improve erythroid cell differentiation from hematopoietic stem cells, which was inhibited by the estrogen receptor (ER) antagonist, ICI 182,780. Moreover, the ASPP 049-activated Epo-Epo receptor (EpoR) complex subsequently induced phosphorylation of EpoR-mediated erythropoiesis pathways: STAT5, MAPK/ERK, and PI3K/AKT in Epo-sensitive UT-7 cells. Taken together, these results suggest that C. comosa extract and ASPP 049 increased erythropoiesis through ER- and EpoR-mediated signaling cascades. Our findings provide insight into the specific interaction between a phytoestrogen diarylheptanoid and Epo-EpoR in a hematopoietic system for the potential treatment of anemia. Full article
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22 pages, 4298 KiB  
Article
Antitumor Properties of a New Macrocyclic Tetranuclear Oxidovanadium(V) Complex with 3-Methoxysalicylidenvaline Ligand
by Mihaela Turtoi, Maria Anghelache, Andrei A. Patrascu, Mariana Deleanu, Geanina Voicu, Mihai Raduca, Florentina Safciuc, Ileana Manduteanu, Manuela Calin and Delia-Laura Popescu
Biomedicines 2022, 10(6), 1217; https://doi.org/10.3390/biomedicines10061217 - 24 May 2022
Cited by 1 | Viewed by 2056
Abstract
A wide variety of metal-based compounds have been obtained and studied for their antitumor activity since the intensely used cytostatic drugs (e.g., cisplatin) failed to accomplish their expected pharmacological properties. Thus, we aimed to develop a new vanadium-based drug and assess its antitumor [...] Read more.
A wide variety of metal-based compounds have been obtained and studied for their antitumor activity since the intensely used cytostatic drugs (e.g., cisplatin) failed to accomplish their expected pharmacological properties. Thus, we aimed to develop a new vanadium-based drug and assess its antitumor properties using the human hepatocarcinoma (HepG2) cell line. The compound was synthesized from vanadyl sulfate, DL-valine, and o-vanillin and was spectrally and structurally characterized (UV-Vis, IR, CD, and single-crystal/powder-XRD). Compound stability in biological media, cell uptake, and the interaction with albumin were assessed. The mechanisms of its antitumor activity were determined compared to cisplatin by performing cytotoxicity, oxidative and mitochondrial status, DNA fragmentation, β-Tubulin synthesis investigation, and cell cycle studies. Herein, we developed a macrocyclic tetranuclear oxidovanadium(V) compound, [(VVO)(L)(CH3O)]4, having coordinated four Schiff base (H2L) ligands, 3-methoxysalicylidenvaline. We showed that [(VVO)(L)(CH3O)]4: (i) has pH-dependent stability in biological media, (ii) binds to albumin in a dose-dependent manner, (iii) is taken up by cells in a time-dependent way, (iv) has a higher capacity to induce cell death compared to cisplatin (IC50 = 6 μM vs. 10 μM), by altering the oxidative and mitochondrial status in HepG2 cells. Unlike cisplatin, which blocks the cell cycle in the S-phase, the new vanadium-based compound arrests it in S and G2/M-phase, whereas no differences in the induction of DNA fragmentation and reduction of β-Tubulin synthesis between the two were determined. Thus, the [(VVO)(L)(CH3O)]4 antitumor mechanism involved corroboration between the generation of oxidative species, mitochondrial dysfunction, degradation of DNA, cell cycle arrest in the S and G2/M-phase, and β-Tubulin synthesis reduction. Our studies demonstrate the potent antitumor activity of [(VVO)(L)(CH3O)]4 and propose it as an attractive candidate for anticancer therapy. Full article
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23 pages, 13874 KiB  
Article
Meleagrin Isolated from the Red Sea Fungus Penicillium chrysogenum Protects against Bleomycin-Induced Pulmonary Fibrosis in Mice
by Sameh S. Elhady, Marwa S. Goda, Eman T. Mehanna, Mahmoud A. Elfaky, Abdulrahman E. Koshak, Ahmad O. Noor, Hanin A. Bogari, Rania T. Malatani, Reda F. A. Abdelhameed and Alaa S. Wahba
Biomedicines 2022, 10(5), 1164; https://doi.org/10.3390/biomedicines10051164 - 18 May 2022
Cited by 12 | Viewed by 2404
Abstract
The Red Sea marine fungus Penicillium chrysogenum (Family: Ascomycota) comprises a panel of chemically diverse natural metabolites. A meleagrin alkaloid was isolated from deep-sediment-derived P. chrysogenum Strain S003 and has been reported to exert antibacterial and cytotoxic activities. The present study aimed to [...] Read more.
The Red Sea marine fungus Penicillium chrysogenum (Family: Ascomycota) comprises a panel of chemically diverse natural metabolites. A meleagrin alkaloid was isolated from deep-sediment-derived P. chrysogenum Strain S003 and has been reported to exert antibacterial and cytotoxic activities. The present study aimed to explore the therapeutic potential of meleagrin on pulmonary fibrosis. Lung fibrosis was induced in mice by a single intratracheal instillation of 2.5 mg/kg bleomycin. Mice were given 5 mg/kg meleagrin daily either for 3 weeks after bleomycin administration in the treatment group or 2 weeks before and 3 weeks after bleomycin administration in the protection group. Bleomycin triggered excessive ROS production, inflammatory infiltration, collagen overproduction and fibrosis. Bleomycin-induced pulmonary fibrosis was attenuated by meleagrin. Meleagrin was noted to restore the oxidant–antioxidant balance, as evidenced by lower MDA contents and higher levels of SOD and catalase activities and GSH content compared to the bleomycin group. Meleagrin also activated the Nrf2/HO-1 antioxidant signaling pathway and inhibited TLR4 and NF-κB gene expression, with a subsequent decreased release of pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ). Additionally, meleagrin inhibited bleomycin-induced apoptosis by abating the activities of pro-apoptotic proteins Bax and caspase-3 while elevating Bcl2. Furthermore, it suppressed the gene expression of α-SMA, TGF-β1, Smad-2, type I collagen and MMP-9, with a concomitant decrease in the protein levels of TGF-β1, α-SMA, phosphorylated Smad-2, MMP-9, elastin and fibronectin. This study revealed that meleagrin’s protective effects against bleomycin-induced pulmonary fibrosis are attributed to its antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic properties. Notably, the use of meleagrin as a protective agent against bleomycin-induced lung fibrosis was more efficient than its use as a treatment agent. Full article
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22 pages, 3821 KiB  
Article
Potent and Broad-Spectrum Bactericidal Activity of a Nanotechnologically Manipulated Novel Pyrazole
by Silvana Alfei, Debora Caviglia, Alessia Zorzoli, Danilo Marimpietri, Andrea Spallarossa, Matteo Lusardi, Guendalina Zuccari and Anna Maria Schito
Biomedicines 2022, 10(4), 907; https://doi.org/10.3390/biomedicines10040907 - 15 Apr 2022
Cited by 5 | Viewed by 1818
Abstract
The antimicrobial potency of the pyrazole nucleus is widely reported these days, and pyrazole derivatives represent excellent candidates for meeting the worldwide need for new antimicrobial compounds against multidrug-resistant (MDR) bacteria. Consequently, 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), recently reported as a weak antiproliferative agent, was considered [...] Read more.
The antimicrobial potency of the pyrazole nucleus is widely reported these days, and pyrazole derivatives represent excellent candidates for meeting the worldwide need for new antimicrobial compounds against multidrug-resistant (MDR) bacteria. Consequently, 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), recently reported as a weak antiproliferative agent, was considered to this end. To overcome the CR232 water solubility issue and allow for the determination of reliable minimum inhibitory concentration values (MICs), we initially prepared water-soluble and clinically applicable CR232-loaded nanoparticles (CR232-G5K NPs), as previously reported. Here, CR232-G5K NPs have been tested on several clinically isolates of Gram-positive and Gram-negative species, including MDR strains. While for CR232 MICs ≥ 128 µg/mL (376.8 µM) were obtained, very low MICs (0.36–2.89 µM) were observed for CR232-G5K NPs against all of the considered isolates, including colistin-resistant isolates of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemases (KPCs)-producing K. pneumoniae (0.72 µM). Additionally, in time–kill experiments, CR232-G5K NPs displayed a rapid bactericidal activity with no significant regrowth after 24 h on all isolates tested, regardless of their difficult-to-treat resistance. Conjecturing a clinical use of CR232-G5K NPs, cytotoxicity experiments on human keratinocytes were performed, determining very favorable selectivity indices. Collectively, due to its physicochemical and biological properties, CR232-G5K NPs could represent a new potent weapon to treat infections sustained by broad spectrum MDR bacteria. Full article
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17 pages, 2596 KiB  
Article
The Nephroprotective Effects of α-Bisabolol in Cisplatin-Induced Acute Kidney Injury in Mice
by Nur Elena Zaaba, Sumaya Beegam, Ozaz Elzaki, Javed Yasin, Bilal Mohamed Nemmar, Badreldin H. Ali, Ernest Adeghate and Abderrahim Nemmar
Biomedicines 2022, 10(4), 842; https://doi.org/10.3390/biomedicines10040842 - 3 Apr 2022
Cited by 8 | Viewed by 2448
Abstract
Cisplatin (CP) treatment has been long associated with the development of acute kidney injury (AKI) through mechanisms involving inflammation and oxidative stress. α-Bisabolol (BIS), a sesquiterpene alcohol isolated from the essential oil of various plants, including chamomile, has garnered popularity lately due to [...] Read more.
Cisplatin (CP) treatment has been long associated with the development of acute kidney injury (AKI) through mechanisms involving inflammation and oxidative stress. α-Bisabolol (BIS), a sesquiterpene alcohol isolated from the essential oil of various plants, including chamomile, has garnered popularity lately due to its antioxidant, anti-inflammatory, and anticancer properties. Therefore, we investigated the nephroprotective effects of BIS in the murine model of CP-induced AKI and the underlying mechanism of action. BALB/c mice were given BIS orally at 25 mg/kg for 7 days. On day 7, they were given a single dose of CP at 20 mg/kg intraperitoneally. BIS treatment continued for 3 more days. The animals were sacrificed at the end of the experiment (day 11). Kidneys, plasma, and urine were collected, and subsequently, various physiological, biochemical, and histological parameters were assessed. BIS has significantly normalized the alterations of water intake, urine volume, relative kidney weight, and the concentrations of urea and creatinine, as well as the creatinine clearance induced by CP treatment. BIS significantly mitigated the effects of CP-induced kidney injury by reducing kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, adiponectin, and cystatin C. Likewise, the renal concentrations of proinflammatory cytokines, tumor necrosis factor α, interleukin (IL)-6 and IL-1β that were elevated in CP group were significantly reduced in mice treated with BIS and CP. A similar significant reduction was also observed in the CP-induced augmented levels of markers of oxidative stress, as well as the metabolite pteridine. Moreover, BIS significantly reduced the CP–induced renal DNA damage, and markedly lessened the acute tubular necrosis observed in kidney histology. Additionally, BIS significantly reduced the CP-induced increase in the phosphorylated nuclear factor κB (NFκB) in the kidney. These data strongly suggest that BIS exerts a protective action against CP-induced nephrotoxicity by mitigating inflammation and oxidative stress through the inhibition of NFκB activation. No overt adverse effects were noted with BIS treatment. Additional investigations should be done to consider BIS as an efficacious nephroprotective agent against CP. Full article
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Review

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21 pages, 1470 KiB  
Review
New Insights into the Use of Empagliflozin—A Comprehensive Review
by Joanna Forycka, Joanna Hajdys, Julia Krzemińska, Piotr Wilczopolski, Magdalena Wronka, Ewelina Młynarska, Jacek Rysz and Beata Franczyk
Biomedicines 2022, 10(12), 3294; https://doi.org/10.3390/biomedicines10123294 - 19 Dec 2022
Cited by 7 | Viewed by 4537
Abstract
Empagliflozin is a relatively new drug that, as an inhibitor of the sodium–glucose cotransporter 2 (SGLT2), causes increased urinary glucose excretion and thus contributes to improved glycemic control, better glucose metabolism, reduced glucotoxicity and insulin resistance. Although its original use was to induce [...] Read more.
Empagliflozin is a relatively new drug that, as an inhibitor of the sodium–glucose cotransporter 2 (SGLT2), causes increased urinary glucose excretion and thus contributes to improved glycemic control, better glucose metabolism, reduced glucotoxicity and insulin resistance. Although its original use was to induce a hypoglycemic effect in patients with type 2 diabetes mellitus (T2DM), empagliflozin has also shown a number of other beneficial effects by demonstrating a nephroprotective effect, and it has proven to be a breakthrough in the treatment of heart failure (HF). Empagliflozin has been shown to reduce hospitalizations for HF and the number of deaths from cardiovascular causes. Empagliflozin treatment also reduces the incidence of renal events, including death from renal causes, as well as the risk of end-stage renal failure. Empagliflozin appears to be a fairly well-tolerated and safe drug. In patients with inadequate glycemic control, empagliflozin used in monotherapy or as an adjunct to therapy effectively lowers fasting blood glucose, postprandial blood glucose, average daily glucose levels, glycated hemoglobin A1C (HbA1C) and also leads to significant weight reduction in patients with T2DM. Unfortunately, there are some limitations, e.g., severe hypersensitivity reaction to the drug and a glomerular filtration rate (GFR) < 30 mL/min/1.73 m2. As with any drug, empagliflozin is also characterized by several side effects among which symptomatic hypotension, troublesome genital fungal infections, urinary tract infections and rare ketoacidosis are characteristic. Full article
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47 pages, 5556 KiB  
Review
Biochemistry of Antioxidants: Mechanisms and Pharmaceutical Applications
by Sonia Losada-Barreiro, Zerrin Sezgin-Bayindir, Fátima Paiva-Martins and Carlos Bravo-Díaz
Biomedicines 2022, 10(12), 3051; https://doi.org/10.3390/biomedicines10123051 - 25 Nov 2022
Cited by 27 | Viewed by 4229
Abstract
Natural antioxidants from fruits and vegetables, meats, eggs and fish protect cells from the damage caused by free radicals. They are widely used to reduce food loss and waste, minimizing lipid oxidation, as well as for their effects on health through pharmaceutical preparations. [...] Read more.
Natural antioxidants from fruits and vegetables, meats, eggs and fish protect cells from the damage caused by free radicals. They are widely used to reduce food loss and waste, minimizing lipid oxidation, as well as for their effects on health through pharmaceutical preparations. In fact, the use of natural antioxidants is among the main efforts made to relieve the pressure on natural resources and to move towards more sustainable food and pharmaceutical systems. Alternative food waste management approaches include the valorization of by-products as a source of phenolic compounds for functional food formulations. In this review, we will deal with the chemistry of antioxidants, including their molecular structures and reaction mechanisms. The biochemical aspects will also be reviewed, including the effects of acidity and temperature on their partitioning in binary and multiphasic systems. The poor bioavailability of antioxidants remains a huge constraint for clinical applications, and we will briefly describe some delivery systems that provide for enhanced pharmacological action of antioxidants via drug targeting and increased bioavailability. The pharmacological activity of antioxidants can be improved by designing nanotechnology-based formulations, and recent nanoformulations include nanoparticles, polymeric micelles, liposomes/proliposomes, phytosomes and solid lipid nanoparticles, all showing promising outcomes in improving the efficiency and bioavailability of antioxidants. Finally, an overview of the pharmacological effects, therapeutic properties and future choice of antioxidants will be incorporated. Full article
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20 pages, 3580 KiB  
Review
Dual Targeting Topoisomerase/G-Quadruplex Agents in Cancer Therapy—An Overview
by Silvia Salerno, Elisabetta Barresi, Emma Baglini, Valeria Poggetti, Sabrina Taliani and Federico Da Settimo
Biomedicines 2022, 10(11), 2932; https://doi.org/10.3390/biomedicines10112932 - 15 Nov 2022
Cited by 3 | Viewed by 2033
Abstract
Topoisomerase (Topo) inhibitors have long been known as clinically effective drugs, while G-quadruplex (G4)-targeting compounds are emerging as a promising new strategy to target tumor cells and could support personalized treatment approaches in the near future. G-quadruplex (G4) is a secondary four-stranded DNA [...] Read more.
Topoisomerase (Topo) inhibitors have long been known as clinically effective drugs, while G-quadruplex (G4)-targeting compounds are emerging as a promising new strategy to target tumor cells and could support personalized treatment approaches in the near future. G-quadruplex (G4) is a secondary four-stranded DNA helical structure constituted of guanine-rich nucleic acids, and its stabilization impairs telomere replication, triggering the activation of several protein factors at telomere levels, including Topos. Thus, the pharmacological intervention through the simultaneous G4 stabilization and Topos inhibition offers a new opportunity to achieve greater antiproliferative activity and circumvent cellular insensitivity and resistance. In this line, dual ligands targeting both Topos and G4 emerge as innovative, efficient agents in cancer therapy. Although the research in this field is still limited, to date, some chemotypes have been identified, showing this dual activity and an interesting pharmacological profile. This paper reviews the available literature on dual Topo inhibitors/G4 stabilizing agents, with particular attention to the structure–activity relationship studies correlating the dual activity with the cytotoxic activity. Full article
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25 pages, 1527 KiB  
Review
Potential and Therapeutic Roles of Diosmin in Human Diseases
by Etimad Huwait and Mohammad Mobashir
Biomedicines 2022, 10(5), 1076; https://doi.org/10.3390/biomedicines10051076 - 6 May 2022
Cited by 41 | Viewed by 10240
Abstract
Because of their medicinal characteristics, effectiveness, and importance, plant-derived flavonoids have been a possible subject of research for many years, particularly in the last decade. Plants contain a huge number of flavonoids, and Diosmin, a flavone glycoside, is one of them. Numerous in-vitro [...] Read more.
Because of their medicinal characteristics, effectiveness, and importance, plant-derived flavonoids have been a possible subject of research for many years, particularly in the last decade. Plants contain a huge number of flavonoids, and Diosmin, a flavone glycoside, is one of them. Numerous in-vitro and in-vivo studies have validated Diosmin’s extensive range of biological capabilities which present antioxidative, antihyperglycemic, anti-inflammatory, antimutagenic, and antiulcer properties. We have presented this review work because of the greater biological properties and influences of Diosmin. We have provided a brief overview of Diosmin, its pharmacology, major biological properties, such as anti-cancer, anti-diabetic, antibacterial, anticardiovascular, liver protection, and neuroprotection, therapeutic approach, potential Diosmin targets, and pathways that are known to be associated with it. Full article
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23 pages, 1438 KiB  
Review
Immune Mechanism of Epileptogenesis and Related Therapeutic Strategies
by María José Aguilar-Castillo, Pablo Cabezudo-García, Nicolas Lundahl Ciano-Petersen, Guillermina García-Martin, Marta Marín-Gracia, Guillermo Estivill-Torrús and Pedro Jesús Serrano-Castro
Biomedicines 2022, 10(3), 716; https://doi.org/10.3390/biomedicines10030716 - 19 Mar 2022
Cited by 10 | Viewed by 3643
Abstract
Immunologic and neuroinflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of [...] Read more.
Immunologic and neuroinflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources, it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. For this reason, we performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways involved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs. Full article
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