Life | Special Issue : New Trends in Pharmaceutical Science

Editorial

Jump to: Research, Review, Other

2 pages, 164 KiB

Open AccessEditorial

New Paradigms in Pharmaceutical Development

by Ramón Cacabelos

Life 2022, 12(9), 1433; https://doi.org/10.3390/life12091433 - 15 Sep 2022

Cited by 1 | Viewed by 1439

Abstract

The main health problems in developed countries are cardiovascular diseases (25–30%), cancer (20–25%) and nervous system disorders (10–15%), which globally account for more than 80% of the morbidity and mortality in the general population [...] Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

Research

Jump to: Editorial, Review, Other

18 pages, 3991 KiB

Open AccessArticle

Dithymoquinone Analogues as Potential Candidate(s) for Neurological Manifestation Associated with COVID-19: A Therapeutic Strategy for Neuro-COVID

by Afrasim Moin, Bader Huwaimel, Ahmed Alobaida, Mohammed Khaled Bin Break, Danish Iqbal, Rahamat Unissa, Qazi Mohammad Sajid Jamal, Talib Hussain, Dinesh C. Sharma and Syed Mohd Danish Rizvi

Life 2022, 12(7), 1076; https://doi.org/10.3390/life12071076 - 19 Jul 2022

Cited by 3 | Viewed by 2243

Abstract

The COVID-19 era has prompted several researchers to search for a linkage between COVID-19 and its associated neurological manifestation. Toll-like receptor 4 (TLR-4) acts as one such connecting link. spike protein of SARS-CoV-2 can bind either to ACE-2 receptors or to TLR-4 receptors, [...] Read more.

The COVID-19 era has prompted several researchers to search for a linkage between COVID-19 and its associated neurological manifestation. Toll-like receptor 4 (TLR-4) acts as one such connecting link. spike protein of SARS-CoV-2 can bind either to ACE-2 receptors or to TLR-4 receptors, leading to aggregation of α-synuclein and neurodegeneration via the activation of various cascades in neurons. Recently, dithymoquinone has been reported as a potent multi-targeting candidate against SARS-CoV-2. Thus, in the present study, dithymoquinone and its six analogues were explored to target 3CL^pro (main protease of SARS-CoV-2), TLR4 and PREP (Prolyl Oligopeptidases) by using the molecular docking and dynamics approach. Dithymoquinone (DTQ) analogues were designed in order to investigate the effect of different chemical groups on its bioactivity. It is noteworthy to mention that attention was given to the feasibility of synthesizing these analogues by a simple photo-dimerisation reaction. The DTQ analogue containing the 4-fluoroaniline moiety [Compound (4)] was selected for further analysis by molecular dynamics after screening via docking-interaction analyses. A YASARA structure tool built on the AMBER14 force field was used to analyze the 100 ns trajectory by taking 400 snapshots after every 250 ps. Moreover, RMSD, RoG, potential energy plots were successfully obtained for each interaction. Molecular docking results indicated strong interaction of compound (4) with 3CL^pro, TLR4 and PREP with a binding energy of −8.5 kcal/mol, −10.8 kcal/mol and −9.5 kcal/mol, respectively, which is better than other DTQ-analogues and control compounds. In addition, compound (4) did not violate Lipinski’s rule and showed no toxicity. Moreover, molecular dynamic analyses revealed that the complex of compound (4) with target proteins was stable during the 100 ns trajectory. Overall, the results predicted that compound (4) could be developed into a potent anti-COVID agent with the ability to mitigate neurological manifestations associated with COVID-19. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

17 pages, 3704 KiB

Open AccessArticle

Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus

by Pardeep Yadav, Sherif A. El-Kafrawy, Mai M. El-Day, Wejdan T. Alghafari, Arwa A. Faizo, Saurabh Kumar Jha, Vivek Dhar Dwivedi and Esam I. Azhar

Life 2022, 12(7), 952; https://doi.org/10.3390/life12070952 - 24 Jun 2022

Cited by 14 | Viewed by 2778

Abstract

The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it [...] Read more.

The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it an attractive target for antiviral drug development. In this study, the natural products from Echinacea angustifolia were retrieved for structure-based virtual screening against JEV–RdRp. The top six compounds (Echinacoside, Echinacin, Rutin, Cynaroside, Quercetagetin 7-glucoside, and Kaempferol-3-glucoside) were obtained based on the highest negative docking score, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and molecular interaction. The computational analysis of these selected compounds against the co-crystallized ligands, i.e., ATP and GTP, were performed. Further, 100 ns molecular dynamic simulation and post-free binding energy calculation of all the selected compounds complexed with JEV–RdRP were performed to check the stability of the complexes. The obtained results showed considerable stability and intermolecular interaction with native ligand-binding site residues of JEV–RdRp. Hence, selected natural compounds are admissible inhibitors of JEV–RdRp protein and can be considered for future antiviral drug development studies. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

0 pages, 2464 KiB

Open AccessArticle

2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation

by Mohamed H. Elsherbeny, Usama M. Ammar, Magda H. Abdellattif, Mohammed A. S. Abourehab, Ahmed Abdeen, Samah F. Ibrahim, Doaa Abdelrahaman, Wessam Mady, Eun Joo Roh and Ahmed Elkamhawy

Life 2022, 12(6), 876; https://doi.org/10.3390/life12060876 - 10 Jun 2022

Cited by 3 | Viewed by 2126 | Correction

Abstract

New quinazoline derivatives were designed based on the structural modification of the reported inhibitors to enhance their selectivity toward Aurora A. The synthesized compounds were tested over Aurora A, and a cytotoxicity assay was performed over NCI cell lines to select the best [...] Read more.

New quinazoline derivatives were designed based on the structural modification of the reported inhibitors to enhance their selectivity toward Aurora A. The synthesized compounds were tested over Aurora A, and a cytotoxicity assay was performed over NCI cell lines to select the best candidate for further evaluation. Compound 6e (2-(3-bromophenyl)-8-fluoroquinazoline-4-carboxylic acid) was the most potent compound among the tested derivatives. A Kinase panel assay was conducted for compound 6e over 14 kinases to evaluate its selectivity profile. Further cell cycle and apoptosis analysis were evaluated for compound 6e over the MCF-7 cell line at its IC₅₀ of 168.78 µM. It arrested the cell cycle at the G1 phase and induced apoptosis. Molecular docking was performed to explore the possible binding mode of compound 6e into the active site. It showed significant binding into the main pocket in addition to potential binding interactions with the key amino acid residues. Accordingly, compound 6e can be considered a potential lead for further structural and molecular optimization of the quinazoline-based carboxylic acid scaffold for Aurora A kinase selective inhibition with apoptosis properties. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

22 pages, 3818 KiB

Open AccessArticle

Computational Investigations on the Natural Small Molecule as an Inhibitor of Programmed Death Ligand 1 for Cancer Immunotherapy

by Geethu S Kumar, Mahmoud Moustafa, Amaresh Kumar Sahoo, Petr Malý and Shiv Bharadwaj

Life 2022, 12(5), 659; https://doi.org/10.3390/life12050659 - 29 Apr 2022

Cited by 4 | Viewed by 3014

Abstract

Several therapeutic monoclonal antibodies approved by the FDA are available against the PD-1/PD-L1 (programmed death 1/programmed death ligand 1) immune checkpoint axis, which has been an unprecedented success in cancer treatment. However, existing therapeutics against PD-L1, including small molecule inhibitors, have certain drawbacks [...] Read more.

Several therapeutic monoclonal antibodies approved by the FDA are available against the PD-1/PD-L1 (programmed death 1/programmed death ligand 1) immune checkpoint axis, which has been an unprecedented success in cancer treatment. However, existing therapeutics against PD-L1, including small molecule inhibitors, have certain drawbacks such as high cost and drug resistance that challenge the currently available anti-PD-L1 therapy. Therefore, this study presents the screening of 32,552 compounds from the Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening followed by binding free energy to refine the ideal conformation of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>−60 kcal/mol) for further computational investigation in comparison to co-crystallized ligand, i.e., JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and end-point binding free energy calculations, the selected natural compounds were marked for substantial stability with PD-L1 via intermolecular interactions (hydrogen and hydrophobic) with essential residues in comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitors in cancer immunotherapy. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Graphical abstract

25 pages, 5922 KiB

Open AccessArticle

Network Pharmacology Study to Reveal the Potentiality of a Methanol Extract of Caesalpinia sappan L. Wood against Type-2 Diabetes Mellitus

by Md. Adnan, Byeong-Bae Jeon, Md. Helal Uddin Chowdhury, Ki-Kwang Oh, Tuhin Das, Md. Nazim Uddin Chy and Dong-Ha Cho

Life 2022, 12(2), 277; https://doi.org/10.3390/life12020277 - 13 Feb 2022

Cited by 14 | Viewed by 5236

Abstract

Caesalpinia sappan L. (CS) is widely used to treat diabetic complications in south-east Asia, specifically in traditional Chinese medicine. This study intends to explain the molecular mechanism of how chemical constituents of CS interrelate with different signaling pathways and receptors involved in T2DM. [...] Read more.

Caesalpinia sappan L. (CS) is widely used to treat diabetic complications in south-east Asia, specifically in traditional Chinese medicine. This study intends to explain the molecular mechanism of how chemical constituents of CS interrelate with different signaling pathways and receptors involved in T2DM. GC-MS was employed to identify the chemical compounds from the methanol extract of CS wood (MECSW). Lipinski’s rule of five was applied, and 33 bioactive constituents have been screened from the CS extract. After that, 124 common targets and 26 compounds associated with T2DM were identified by mining several public databases. Protein–protein interactions and compound-target network were constructed using the STRING database and Cytoscape tool. Protein–protein interactions were identified in 121 interconnected nodes active in T2DM and peroxisome proliferator-activated receptor gamma (PPARG) as key target receptors. Furthermore, pathway compound target (PCT) analysis using the merger algorithm plugin of Cytoscape revealed 121 nodes from common T2DM targets, 33 nodes from MECSW compounds and 9 nodes of the KEGG pathway. Moreover, network topology analysis determined “Fisetin tetramethyl ether” as the key chemical compound. The DAVID online tool determined seven signaling receptors, among which PPARG was found most significant in T2DM progression. Gene ontology and KEGG pathway analysis implied the involvement of nine pathways, and the peroxisome proliferator-activated receptor (PPAR) pathway was selected as the hub signaling pathway. Finally, molecular docking and quantum chemistry analysis confirmed the strong binding affinity and reactive chemical nature of fisetin tetramethyl ether with target receptors exceeding that of the conventional drug (metformin), PPARs agonist (rosiglitazone) and co-crystallized ligands, indicating that fisetin could be a potential drug of choice in T2DM management. This study depicts the interrelationship of the bioactive compounds of MECSW with the T2DM-associated signaling pathways and target receptors. It also proposes a more pharmaceutically effective substance, fisetin tetramethyl ether, over the standard drug that activates PPARG protein in the PPAR signaling pathway of T2DM. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

15 pages, 4054 KiB

Open AccessArticle

Pharmacological Effect of GABA Analogues on GABA-ϱ2 Receptors and Their Subtype Selectivity

by Moawiah M. Naffaa, David E. Hibbs, Mary Chebib and Jane R. Hanrahan

Life 2022, 12(1), 127; https://doi.org/10.3390/life12010127 - 17 Jan 2022

Cited by 3 | Viewed by 2157

Abstract

GABA

ϱ

receptors are distinctive GABAergic receptors from other ionotropic GABA_A and metabotropic GABA_B receptors in their pharmacological, biochemical, and electrophysiological properties. Although GABA-

ϱ

1 receptors are the most studied in this subfamily, GABA-

ϱ

2 receptors are widely distributed [...] Read more.

GABA

ϱ

receptors are distinctive GABAergic receptors from other ionotropic GABA_A and metabotropic GABA_B receptors in their pharmacological, biochemical, and electrophysiological properties. Although GABA-

ϱ

1 receptors are the most studied in this subfamily, GABA-

ϱ

2 receptors are widely distributed in the brain and are considered a potential target for treating neurological disorders such as stroke. The structure of GABA-

ϱ

2 receptors and their pharmacological features are poorly studied. We generated the first homology model of GABA-

ϱ

2 channel, which predicts similar major interactions of GABA with the binding-site residues in GABA-

ϱ

1 and GABA-

ϱ

2 channels. We also investigated the pharmacological properties of several GABA analogues on the activity of GABA-

ϱ

2 receptors. In comparison to their pharmacological effect on GABA-

ϱ

1 receptors, the activation effect of these ligands and their potentiation/inhibition impact on GABA response have interestingly shown inter-selectivity between the two GABA-

ϱ

receptors. Our results suggest that several GABA analogues can be used as research tools to study the distinctive physiology of GABA-

ϱ

1 and GABA-

ϱ

2 receptors. Furthermore, their partial agonist effect may hold promise for the future discovery of selective modulatory agents on GABA_A receptors. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

18 pages, 10507 KiB

Open AccessArticle

AntiGan: An Epinutraceutical Bioproduct with Antitumor Properties in Cultured Cell Lines

by Olaia Martínez-Iglesias, Ivan Carrera, Vinogran Naidoo and Ramón Cacabelos

Life 2022, 12(1), 97; https://doi.org/10.3390/life12010097 - 10 Jan 2022

Cited by 2 | Viewed by 2496

Abstract

Novel and effective chemotherapeutic agents are needed to improve cancer treatment. Epidrugs are currently used for cancer therapy but also exhibit toxicity. Targeting the epigenetic apparatus with bioproducts may aid cancer prevention and treatment. To determine whether the lipoprotein marine extract AntiGan shows [...] Read more.

Novel and effective chemotherapeutic agents are needed to improve cancer treatment. Epidrugs are currently used for cancer therapy but also exhibit toxicity. Targeting the epigenetic apparatus with bioproducts may aid cancer prevention and treatment. To determine whether the lipoprotein marine extract AntiGan shows epigenetic and antitumor effects, cultured HepG2 (hepatocellular carcinoma) and HCT116 (colorectal carcinoma) cell lines were treated with AntiGan (10, 50, 100, and to 500 µg/mL) for 24 h, 48 h, and 72 h. AntiGan (10 µg/mL) reduced cell viability after 48 h and increased Bax expression; AntiGan (10 and 50 µg/mL) increased caspase-3 immunoreactivity in HepG2 and HCT116 cells. AntiGan (10 and 50 µg/mL) attenuated COX-2 and IL-17 expression in both cell lines. AntiGan (10 µg/mL) increased 5mC levels in both cell types and reduced DNMT1 and DNMT3a expression in these cells. AntiGan (10 and 50 µg/mL) promoted DNMT3a immunoreactivity and reduced SIRT1 mRNA expression in both cell types. In HCT116 cells treated with AntiGan (10 µg/mL), SIRT1 immunoreactivity localized to nuclei and the cytoplasm; AntiGan (50 µg/mL) increased cytoplasmic SIRT1 localization in HCT116 cells. AntiGan is a novel antitumoral bioproduct with epigenetic properties (epinutraceutical) for treating liver and colorectal cancer. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

16 pages, 2203 KiB

Open AccessArticle

Acute and Delayed Doxorubicin-Induced Myocardiotoxicity Associated with Elevation of Cardiac Biomarkers, Depletion of Cellular Antioxidant Enzymes, and Several Histopathological and Ultrastructural Changes

by Alaa Abdelatty, Mohamed S. Ahmed, Mona A. Abdel-Kareem, Mohamed Dmerdash, Rehab Mady, Ahmed S. Saad, Ashraf Albrakati, Ehab Kotb Elmahallawy, Ahmed Elsawak and Walied Abdo

Life 2021, 11(9), 880; https://doi.org/10.3390/life11090880 - 27 Aug 2021

Cited by 9 | Viewed by 2642

Abstract

Doxorubicin (DOX; Adricin) is an anthracycline antibiotic, which is an efficient anticancer chemotherapeutic agent that targets many types of adult and pediatric tumors, such as breast cancer, leukemia, and lymphomas. However, use of DOX is limited due to its cardiotoxic effects. This study [...] Read more.

Doxorubicin (DOX; Adricin) is an anthracycline antibiotic, which is an efficient anticancer chemotherapeutic agent that targets many types of adult and pediatric tumors, such as breast cancer, leukemia, and lymphomas. However, use of DOX is limited due to its cardiotoxic effects. This study sequentially investigated the mechanistic pathways of the cardiotoxic process of DOX in rats at different post-treatment periods using cumulative dose, which is used in therapeutic regimes. In this regard, 56 male albino rats were used for the experiment. The experimental animals were divided into seven groups (n = 8/group) based on dose and sacrifice schedule as follows: G1 (2 mg/kg body weight [BW] and sacrificed at day 4), G2 (4 mg/kg BW and sacrificed at day 8), G3 (6 mg/kg BW and sacrificed at day 15), G4 (8 mg/kg BW and sacrificed at day 30), G5 (10 mg/kg BW and sacrificed at day 60), G6 (10 mg/kg BW and sacrificed at day 90), and G7 (10 mg/kg BW and sacrificed at day 120). As expected, G1, G2, and G3-treated groups revealed features of acute toxic myocarditis associated with degenerative and necrotic changes in myocytes, mitochondrial damage, elevation of cardiac biomarkers, and depletion of cellular antioxidant enzymes. However, these changes increased in severity with subsequent treatment with the same dose until reaching a cumulative dose of 10 mg/kg BW for 30 d. Furthermore, after a cumulative dose of 10 mg/kg BW with a withdrawal period of 2–3 months, various predominant changes in chronicity were reported, such as disorganization and atrophy of myocytes, condensation and atrophy of mitochondria, degranulation of mast cells, and fibrosis with occasional focal necrosis, indicating incomplete elimination of DOX and/or its metabolites. Altogether, these data provide interesting observations associated with the cardiotoxic process of DOX in rats that would help understand the accompanying changes underlying the major toxic effects of the drug. Future research is suggested to explore more about the dose-dependent mechanisms of such induced toxicity of DOX that would help determine the proper doses and understand the resulting cardiomyopathy. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

15 pages, 6380 KiB

Open AccessArticle

Identification of Lead Compounds against Scm (fms10) in Enterococcus faecium Using Computer Aided Drug Designing

by Muhammad Asif Rasheed, Muhammad Nasir Iqbal, Salina Saddick, Iqra Ali, Falak Sher Khan, Sumaira Kanwal, Dawood Ahmed, Muhammad Ibrahim, Umara Afzal and Muhammad Awais

Life 2021, 11(2), 77; https://doi.org/10.3390/life11020077 - 21 Jan 2021

Cited by 79 | Viewed by 5828

Abstract

(1) Background: Enterococcus faecium DO is an environmental microbe, which is a mesophilic, facultative, Gram-positive, and multiple habitat microorganism. Enterococcus faecium DO is responsible for many diseases in human. The fight against infectious diseases is confronted by the development of multiple drug resistance [...] Read more.

(1) Background: Enterococcus faecium DO is an environmental microbe, which is a mesophilic, facultative, Gram-positive, and multiple habitat microorganism. Enterococcus faecium DO is responsible for many diseases in human. The fight against infectious diseases is confronted by the development of multiple drug resistance in E. faecium. The focus of this research work is to identify a novel compound against this pathogen by using bioinformatics tools and technology. (2) Methods: We screened the proteome (accession No. PRJNA55353) information from the genome database of the National Centre for Biotechnology Information (NCBI) and suggested a potential drug target. I-TASSER was used to predict the three-dimensional structure of the protein, and the structure was optimized and minimized by different tools. PubChem and ChEBI were used to retrieve the inhibitors. Pharmacophore modeling and virtual screening were performed to identify novel compounds. Binding interactions of compounds with target protein were checked using LigPlot. pkCSM, SwissADME, and ProTox-II were used for adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. (3) Results: Novel selected compounds have improved absorption and have better ADMET properties. Based on our results, the chemically identified inhibitor ZINC48942 targeted the receptor that can inhibit the activity of infection in E. faecium. This research work will be beneficial for the scientific community and could aid in the design of a new drug against E. faecium infections. (4) Conclusions: It was observed that novel compounds are potential inhibitors with more efficacy and fewer side effects. This research work will help researchers in testing and identification of these chemicals useful against E. faecium. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

22 pages, 1205 KiB

Open AccessReview

The Immune System as a Therapeutic Target for Alzheimer’s Disease

by Tarek Zieneldien, Janice Kim, Darrell Sawmiller and Chuanhai Cao

Life 2022, 12(9), 1440; https://doi.org/10.3390/life12091440 - 16 Sep 2022

Cited by 14 | Viewed by 3302

Abstract

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder and is the most common cause of dementia. Furthermore, aging is considered the most critical risk factor for AD. However, despite the vast amount of research and resources allocated to the understanding and development of [...] Read more.

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder and is the most common cause of dementia. Furthermore, aging is considered the most critical risk factor for AD. However, despite the vast amount of research and resources allocated to the understanding and development of AD treatments, setbacks have been more prominent than successes. Recent studies have shown that there is an intricate connection between the immune and central nervous systems, which can be imbalanced and thereby mediate neuroinflammation and AD. Thus, this review examines this connection and how it can be altered with AD. Recent developments in active and passive immunotherapy for AD are also discussed as well as suggestions for improving these therapies moving forward. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

17 pages, 738 KiB

Open AccessReview

Effects of Cannabidiol on Locomotor Activity

by Fabrizio Calapai, Luigi Cardia, Gioacchino Calapai, Debora Di Mauro, Fabio Trimarchi, Ilaria Ammendolia and Carmen Mannucci

Life 2022, 12(5), 652; https://doi.org/10.3390/life12050652 - 27 Apr 2022

Cited by 9 | Viewed by 4900

Abstract

Cannabidiol (CBD) is the second cannabinoid, in order of importance after Δ9-tetrahydrocannabinol (THC), from Cannabis sativa. Unlike THC, CBD does not cause psychotomimetic effects, and although these compounds have the same chemical formula, their pharmacological characteristics are not equivalent. Preclinical studies suggest [...] Read more.

Cannabidiol (CBD) is the second cannabinoid, in order of importance after Δ9-tetrahydrocannabinol (THC), from Cannabis sativa. Unlike THC, CBD does not cause psychotomimetic effects, and although these compounds have the same chemical formula, their pharmacological characteristics are not equivalent. Preclinical studies suggest that CBD has anti-inflammatory, analgesic, anxiolytic, antiemetic, anticonvulsant, and antipsychotic properties and influences the sleep–wake cycle. The evaluation of effects on spontaneous motor activity is crucial in experimental pharmacology, and the careful measurement of laboratory animal movement is an established method to recognize the effects of stimulant and depressant drugs. The potential influence of CBD on locomotor activity has been investigated through numerous in vivo experiments. However, there is no clear picture of the impact of CBD on these issues, even though it is administered alone for medical uses and sold with THC as a drug for pain caused by muscle spasms in multiple sclerosis, and it was recently licensed as a drug for severe forms of infantile epilepsy. On this basis, with the aim of developing deeper knowledge of this issue, scientific data on CBD’s influence on locomotor activity are discussed here. We conducted research using PubMed, Scopus, Google Scholar, and a search engine for literature between January 2009 and December 2021 on life sciences and biomedical topics using the keywords “motor activity”, “locomotor activity”, and “locomotion” in combination with “cannabidiol”. In this article, we discuss findings describing the effects on locomotor activity of the CBD precursor cannabidiolic acid and of CBD alone or in combination with THC, together with the effects of CBD on locomotor modifications induced by diseases and on locomotor changes induced by other substances. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

38 pages, 2969 KiB

Open AccessEditor’s ChoiceReview

Personalized Management and Treatment of Alzheimer’s Disease

by Ramón Cacabelos, Vinogran Naidoo, Olaia Martínez-Iglesias, Lola Corzo, Natalia Cacabelos, Rocío Pego and Juan C. Carril

Life 2022, 12(3), 460; https://doi.org/10.3390/life12030460 - 21 Mar 2022

Cited by 8 | Viewed by 4413

Abstract

Alzheimer’s disease (AD) is a priority health problem with a high cost to society and a large consumption of medical and social resources. The management of AD patients is complex and multidisciplinary. Over 90% of patients suffer from concomitant diseases and require personalized [...] Read more.

Alzheimer’s disease (AD) is a priority health problem with a high cost to society and a large consumption of medical and social resources. The management of AD patients is complex and multidisciplinary. Over 90% of patients suffer from concomitant diseases and require personalized therapeutic regimens to reduce adverse drug reactions (ADRs), drug–drug interactions (DDIs), and unnecessary costs. Men and women show substantial differences in their AD-related phenotypes. Genomic, epigenetic, neuroimaging, and biochemical biomarkers are useful for predictive and differential diagnosis. The most frequent concomitant diseases include hypertension (>25%), obesity (>70%), diabetes mellitus type 2 (>25%), hypercholesterolemia (40%), hypertriglyceridemia (20%), metabolic syndrome (20%), hepatobiliary disorder (15%), endocrine/metabolic disorders (>20%), cardiovascular disorder (40%), cerebrovascular disorder (60–90%), neuropsychiatric disorders (60–90%), and cancer (10%). Over 90% of AD patients require multifactorial treatments with risk of ADRs and DDIs. The implementation of pharmacogenetics in clinical practice can help optimize the limited therapeutic resources available to treat AD and personalize the use of anti-dementia drugs, in combination with other medications, for the treatment of concomitant disorders. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

15 pages, 1882 KiB

Open AccessReview

Nitrogen-Based Heterocyclic Compounds: A Promising Class of Antiviral Agents against Chikungunya Virus

by Andreza C. Santana, Ronaldo C. Silva Filho, José C. J. M. D. S. Menezes, Diego Allonso and Vinícius R. Campos

Life 2021, 11(1), 16; https://doi.org/10.3390/life11010016 - 30 Dec 2020

Cited by 8 | Viewed by 4749

Abstract

Arboviruses, in general, are a global threat due to their morbidity and mortality, which results in an important social and economic impact. Chikungunya virus (CHIKV), one of the most relevant arbovirus currently known, is a re-emergent virus that causes a disease named chikungunya [...] Read more.

Arboviruses, in general, are a global threat due to their morbidity and mortality, which results in an important social and economic impact. Chikungunya virus (CHIKV), one of the most relevant arbovirus currently known, is a re-emergent virus that causes a disease named chikungunya fever, characterized by a severe arthralgia (joint pains) that can persist for several months or years in some individuals. Until now, no vaccine or specific antiviral drug is commercially available. Nitrogen heterocyclic scaffolds are found in medications, such as aristeromycin, favipiravir, fluorouracil, 6-azauridine, thioguanine, pyrimethamine, among others. New families of natural and synthetic nitrogen analogous compounds are reported to have significant anti-CHIKV effects. In the present work, we focus on these nitrogen-based heterocyclic compounds as an important class with CHIKV antiviral activity. We summarize the present understanding on this class of compounds against CHIKV and also present their possible mechanism of action. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

2 pages, 140 KiB

Open AccessCorrection

Correction: Elsherbeny et al. 2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation. Life 2022, 12, 876

by Mohamed H. Elsherbeny, Usama M. Ammar, Magda H. Abdellattif, Mohammed A. S. Abourehab, Ahmed Abdeen, Samah F. Ibrahim, Doaa Abdelrahaman, Wessam Mady, Eun Joo Roh and Ahmed Elkamhawy

Life 2024, 14(4), 423; https://doi.org/10.3390/life14040423 - 22 Mar 2024

Viewed by 816

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

15 pages, 937 KiB

Open AccessConcept Paper

The Case for Clinical Trials with Novel GABAergic Drugs in Diabetes Mellitus and Obesity

by Ferenc A. Antoni

Life 2022, 12(2), 322; https://doi.org/10.3390/life12020322 - 21 Feb 2022

Cited by 5 | Viewed by 3424

Abstract

Obesity and diabetes mellitus have become the surprising menaces of relative economic well-being worldwide. Gamma amino butyric acid (GABA) has a prominent role in the control of blood glucose, energy homeostasis as well as food intake at several levels of regulation. The effects [...] Read more.

Obesity and diabetes mellitus have become the surprising menaces of relative economic well-being worldwide. Gamma amino butyric acid (GABA) has a prominent role in the control of blood glucose, energy homeostasis as well as food intake at several levels of regulation. The effects of GABA in the body are exerted through ionotropic GABA_A and metabotropic GABA_B receptors. This treatise will focus on the pharmacologic targeting of GABA_A receptors to reap beneficial therapeutic effects in diabetes mellitus and obesity. A new crop of drugs selectively targeting GABA_A receptors has been under investigation for efficacy in stroke recovery and cognitive deficits associated with schizophrenia. Although these trials have produced mixed outcomes the compounds are safe to use in humans. Preclinical evidence is summarized here to support the rationale of testing some of these compounds in diabetic patients receiving insulin in order to achieve better control of blood glucose levels and to combat the decline of cognitive performance. Potential therapeutic benefits could be achieved (i) By resetting the hypoglycemic counter-regulatory response; (ii) Through trophic actions on pancreatic islets, (iii) By the mobilization of antioxidant defence mechanisms in the brain. Furthermore, preclinical proof-of-concept work, as well as clinical trials that apply the novel GABA_A compounds in eating disorders, e.g., olanzapine-induced weight-gain, also appear warranted. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

► Show Figures

Figure 1

Journal Menu

Journal Browser

New Trends in Pharmaceutical Science

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (16 papers)

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI