Exploration of Drug Science

Open Access

Editorial

Drug discovery: a multifactorial ecosystem

Fernando Albericio

Published: January 01, 2023 Explor Drug Sci. 2023;1:1–5
DOI: https://doi.org/10.37349/eds.2022.00001

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Commentary

Could flavonoid aglycones prevent the absorption of flavonoid glycosides by inhibiting sodium-dependent glucose transporter-1 in the small intestine?

Flavonoids present a large group of natural polyphenols with numerous important health benefits for preventing and treating a diverse variety of pathological conditions. However, the actual therapeu [...] Read more.

Katrin Sak

Published: August 30, 2023 Explor Drug Sci. 2023;1:287–291
DOI: https://doi.org/10.37349/eds.2023.00019
This article belongs to the special issue Preventive and Therapeutic Potential of Nutraceuticals in Non-communicable Diseases

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Case Report

Single or multiple treatments with lusutrombopag in subjects with thrombocytopenia and chronic liver disease needing an invasive procedure

Thrombocytopenia is one of the most frequent implications of liver cirrhosis. This condition, when present in the severe form [platelet count (PLT) less than 50 × 109/L] correlates, with an increas [...] Read more.

Davide Scalabrini ... Pietro Andreone

Published: August 30, 2023 Explor Drug Sci. 2023;1:292–298
DOI: https://doi.org/10.37349/eds.2023.00020
This article belongs to the special issue Innovative Therapeutics in Hepato-Gastroenterology

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Original Article

Electrochemical properties of hydroxyapatite immobilization material for potential cytosensor fabrication

Aim: The biorecognition unit of an electrochemical biosensor requires molecules that are immobilised to serve as a bridge between the recognition unit and the transducing surface. Unique material [...] Read more.

Dennis Adusei ... Elvis K. Tiburu

Published: September 21, 2023 Explor Drug Sci. 2023;1:299–311
DOI: https://doi.org/10.37349/eds.2023.00021

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Case Report

Grade IV oral mucositis treatment with Brazilian green propolis mucoadherent gel

Green propolis is collected by Apis mellifera from the flowers and buds of Baccharis dracunculifolia. It has several chemical compounds that confer anti-inflammatory, antimicrobial, healing, and ant [...] Read more.

Diogo Alvarenga Silva ... Vagner Rodrigues Santos

Published: October 9, 2023 Explor Drug Sci. 2023;1:312–321
DOI: https://doi.org/10.37349/eds.2023.00022

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Original Article

Late-stage diversification strategy for the synthesis of peptide acids and amides using hydrazides

Aim: Modification of the C-terminus of a peptide to improve its properties, particularly after constructing the peptide chain, has great promise in the development of peptide therapeutics. This s [...] Read more.

Aim: Modification of the C-terminus of a peptide to improve its properties, particularly after constructing the peptide chain, has great promise in the development of peptide therapeutics. This study discusses the development of a late-stage diversification method for synthesizing peptide acids and amides from hydrazides which can serve as a common precursor. Methods: Peptide hydrazides were synthesized solely by using conventional solid-phase peptide synthesis (SPPS). Hydrazides were subjected to oxidation by potassium peroxymonosulfate (Oxone) to afford carboxylic acids. Azidation of hydrazides using sodium nitrite (NaNO2) under acidic conditions, followed by the addition of β-mercaptoethanol (BME), could also be used to generate carboxylic acids. For the preparation of peptide amides, azides that can be prepared from hydrazides were reacted with ammonium acetate (NH4OAc) or tris(2-carboxyethyl)phosphine (TCEP)∙hydrochloride (HCl) to develop the products through ammonolysis or a Staudinger reaction, which produces iminophosphorane from an azide and a phosphine. The antimicrobial activity of modelin-5 derivatives synthesized from the corresponding hydrazides was evaluated by the colony count of Escherichia coli (E. coli) after treatment with the peptides. Results: Oxone oxidation yielded the corresponding acids rapidly although oxidation-prone amino acids were incompatible. Azidation and subsequent treatment with BME afforded peptide acids an acceptable yield even in sequences containing amino acids that are prone to oxidation. Both methods for conversion of hydrazides to amides were found to afford the desired products in good yield and compatibility. The conditions that were developed were adapted to the synthesis of modelin-5 derivatives from the corresponding hydrazides, yielding late-stage production of the desired peptides. The amides of the resulting peptide showed more potent activity against E. coli than the acid form, and the most potent activity was observed from the hydrazide. Conclusions: The developed protocols allow hydrazides to be converted to acids or amides, enabling late-stage diversification of peptide C-terminal residues.

Shoko Tanaka ... Kohei Sato

Published: October 09, 2023 Explor Drug Sci. 2023;1:322–335
DOI: https://doi.org/10.37349/eds.2023.00023
This article belongs to the special issue Bioactive Peptides discovery and development

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Aim: Modification of the C-terminus of a peptide to improve its properties, particularly after constructing the peptide chain, has great promise in the development of peptide therapeutics. This study discusses the development of a late-stage diversification method for synthesizing peptide acids and amides from hydrazides which can serve as a common precursor. Methods: Peptide hydrazides were synthesized solely by using conventional solid-phase peptide synthesis (SPPS). Hydrazides were subjected to oxidation by potassium peroxymonosulfate (Oxone) to afford carboxylic acids. Azidation of hydrazides using sodium nitrite (NaNO2) under acidic conditions, followed by the addition of β-mercaptoethanol (BME), could also be used to generate carboxylic acids. For the preparation of peptide amides, azides that can be prepared from hydrazides were reacted with ammonium acetate (NH4OAc) or tris(2-carboxyethyl)phosphine (TCEP)∙hydrochloride (HCl) to develop the products through ammonolysis or a Staudinger reaction, which produces iminophosphorane from an azide and a phosphine. The antimicrobial activity of modelin-5 derivatives synthesized from the corresponding hydrazides was evaluated by the colony count of Escherichia coli (E. coli) after treatment with the peptides. Results: Oxone oxidation yielded the corresponding acids rapidly although oxidation-prone amino acids were incompatible. Azidation and subsequent treatment with BME afforded peptide acids an acceptable yield even in sequences containing amino acids that are prone to oxidation. Both methods for conversion of hydrazides to amides were found to afford the desired products in good yield and compatibility. The conditions that were developed were adapted to the synthesis of modelin-5 derivatives from the corresponding hydrazides, yielding late-stage production of the desired peptides. The amides of the resulting peptide showed more potent activity against E. coli than the acid form, and the most potent activity was observed from the hydrazide. Conclusions: The developed protocols allow hydrazides to be converted to acids or amides, enabling late-stage diversification of peptide C-terminal residues.

Open Access

Review

Phytochemicals for mitigating the COVID-19 crisis: evidence from pre-clinical and clinical studies

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019 quickly escalated to pandemic levels and had a severe impact on public health. There are 761 m [...] Read more.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019 quickly escalated to pandemic levels and had a severe impact on public health. There are 761 million confirmed coronavirus disease 2019 (COVID-19) cases, with over 6.88 million deaths worldwide till March 2023. Severe cases of the disease caused critical respiratory failure followed by multiorgan involvement. Clinical escalation of COVID-19 has been correlated with markedly increased plasma inflammatory markers [e.g., C-reactive protein (CRP)] and pro-inflammatory cytokine levels [e.g., interleukin (IL)-6, tumor necrosis factor-α (TNF-α)]. Therapeutic options have mostly utilized corticosteroids, antivirals (e.g., remdesivir), and monoclonal antibody-based immunomodulation (e.g., tocilizumab). These existing treatments have adverse side effects, inadequate efficacy, and limitations in administering to patients with comorbidities and other underlying diseases. Monoclonal antibody-based therapies and some of the antivirals are very costly. Many phytochemicals have previously reported anti-inflammatory, antiviral, and antioxidant properties. Studying the effectiveness of such phytochemicals against COVID-19 and identifying new plant-derived molecules with antiviral properties have been a focus since the SARS-CoV-2 outbreak. This review article has documented in vitro, in vivo, and clinical studies encompassing 28 different phytochemicals belonging to various chemical groups (e.g., polyphenols, alkaloids, terpenes) that show anti-COVID-19 activity. These findings suggest that multiple phytochemicals can interfere with virus entry and replication inside the host cell. Many of them can protect from cytokine storm by acting on intracellular signalling pathways in addition to inhibiting virus multiplication. Phytochemicals may prove useful in alleviating post-COVID complications associated with kidney injury, and central nervous system complications, as well. Plant-derived compounds are usually cheaper and have fewer side effects. But, developing new formulations with better absorption and bioavailability remains a priority. This review informs the readers of the current status and indicates the ongoing research in this highly relevant field.

Atri Das ... Shantanabha Das

Published: October 24, 2023 Explor Drug Sci. 2023;1:336–376
DOI: https://doi.org/10.37349/eds.2023.00024
This article belongs to the special issue Exploring Potential Drugs from Natural Products

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The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019 quickly escalated to pandemic levels and had a severe impact on public health. There are 761 million confirmed coronavirus disease 2019 (COVID-19) cases, with over 6.88 million deaths worldwide till March 2023. Severe cases of the disease caused critical respiratory failure followed by multiorgan involvement. Clinical escalation of COVID-19 has been correlated with markedly increased plasma inflammatory markers [e.g., C-reactive protein (CRP)] and pro-inflammatory cytokine levels [e.g., interleukin (IL)-6, tumor necrosis factor-α (TNF-α)]. Therapeutic options have mostly utilized corticosteroids, antivirals (e.g., remdesivir), and monoclonal antibody-based immunomodulation (e.g., tocilizumab). These existing treatments have adverse side effects, inadequate efficacy, and limitations in administering to patients with comorbidities and other underlying diseases. Monoclonal antibody-based therapies and some of the antivirals are very costly. Many phytochemicals have previously reported anti-inflammatory, antiviral, and antioxidant properties. Studying the effectiveness of such phytochemicals against COVID-19 and identifying new plant-derived molecules with antiviral properties have been a focus since the SARS-CoV-2 outbreak. This review article has documented in vitro, in vivo, and clinical studies encompassing 28 different phytochemicals belonging to various chemical groups (e.g., polyphenols, alkaloids, terpenes) that show anti-COVID-19 activity. These findings suggest that multiple phytochemicals can interfere with virus entry and replication inside the host cell. Many of them can protect from cytokine storm by acting on intracellular signalling pathways in addition to inhibiting virus multiplication. Phytochemicals may prove useful in alleviating post-COVID complications associated with kidney injury, and central nervous system complications, as well. Plant-derived compounds are usually cheaper and have fewer side effects. But, developing new formulations with better absorption and bioavailability remains a priority. This review informs the readers of the current status and indicates the ongoing research in this highly relevant field.

Open Access

Review

Therapeutic proteins immunogenicity: a peptide point of view

Protein therapeutics are extensively used in the treatment of autoimmune diseases, but a subset of patients appears to be refractory to these treatments, mainly due to the development of an immune r [...] Read more.

Feliciana Real-Fernandez ... Paolo Rovero

Published: October 26, 2023 Explor Drug Sci. 2023;1:377–387
DOI: https://doi.org/10.37349/eds.2023.00025
This article belongs to the special issue Bioactive Peptides discovery and development

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Original Article

Creation and interpretation of machine learning models for aqueous solubility prediction

Aim: Solubility prediction is an essential factor in rational drug design and many models have been developed with machine learning (ML) methods to enhance the predictive ability. However, most o [...] Read more.

Minyi Su, Enric Herrero

Published: October 30, 2023 Explor Drug Sci. 2023;1:388–404
DOI: https://doi.org/10.37349/eds.2023.00026
This article belongs to the special issue Machine Learning for Drug Science

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Editorial

Machine learning for drug science

Walter F. de Azevedo Jr.

Published: April 16, 2023 Explor Drug Sci. 2023;1:77–80
DOI: https://doi.org/10.37349/eds.2023.00007
This article belongs to the special issue Machine Learning for Drug Science

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Review

Focused ultrasound for treatment of peripheral brain tumors

Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) t [...] Read more.

Phillip Mitchell Johansen ... Brandon Lucke-Wold

Published: April 28, 2023 Explor Drug Sci. 2023;1:107–125
DOI: https://doi.org/10.37349/eds.2023.00009

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Review

Nano theranostics involved in bladder cancer treatment

Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the inte [...] Read more.

Kunpeng Liu ... Qingsong Yu

Published: April 28, 2023 Explor Drug Sci. 2023;1:81–106
DOI: https://doi.org/10.37349/eds.2023.00008
This article belongs to the special issue Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics

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Original Article

Heterogeneous graph convolutional neural network for protein-ligand scoring

Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and [...] Read more.

Kevin Crampon ... Luiz Angelo Steffenel

Published: April 30, 2023 Explor Drug Sci. 2023;1:126–139
DOI: https://doi.org/10.37349/eds.2023.00010
This article belongs to the special issue Machine Learning for Drug Science

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Review

Nature-inspired and medicinally relevant short peptides

Peptides constitute an important component of Nature’s pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered th [...] Read more.

Maria G. Ciulla ... Kamal Kumar

Published: June 27, 2023 Explor Drug Sci. 2023;1:140–171
DOI: https://doi.org/10.37349/eds.2023.00011
This article belongs to the special issue Exploring Potential Drugs from Natural Products

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Original Article

Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1

Aim: Identification of small bioactive regions in proteins and peptides can be useful information in drug design studies. The current study has shown that an inter-cysteine loop of the N-terminal [...] Read more.

Rozita Takjoo ... Norelle L. Daly

Published: June 30, 2023 Explor Drug Sci. 2023;1:172–179
DOI: https://doi.org/10.37349/eds.2023.00012
This article belongs to the special issue Exploring Potential Drugs from Natural Products

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Review

Approved antibacterial drugs in the last 10 years: from the bench to the clinic

Bacterial infections constitute one of the major cases of primary medical incidences worldwide. Historically, the fight against bacterial infections in humans has been an ongoing battle, due to the [...] Read more.

Miguel García-Castro ... Juan Manuel López-Romero

Published: June 30, 2023 Explor Drug Sci. 2023;1:180–209
DOI: https://doi.org/10.37349/eds.2023.00013
This article belongs to the special issue Exploring Potential Drugs from Natural Products

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Original Article

A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli

Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a [...] Read more.

Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed. Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy. Results: Peptide zp39 presented an amphiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, > 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%. Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections.

Ping Zeng ... Lanhua Yi

Published: June 30, 2023 Explor Drug Sci. 2023;1:210–220
DOI: https://doi.org/10.37349/eds.2023.00014
This article belongs to the special issue Bioactive Peptides discovery and development

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Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed. Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy. Results: Peptide zp39 presented an amphiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, > 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%. Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections.

Open Access

Review

The protective role of GLP-1 in neuro-ophthalmology

Despite recent advancements in the field of neuro-ophthalmology, the rising rates of neurological and ophthalmological conditions, mismatches between supply and demand of clinicians, and an aging po [...] Read more.

Sohum Sheth ... Brandon Lucke-Wold

Published: August 28, 2023 Explor Drug Sci. 2023;1:221–238
DOI: https://doi.org/10.37349/eds.2023.00015

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Review

Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes

Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty [...] Read more.

Amedeo Lonardo

Published: August 28, 2023 Explor Drug Sci. 2023;1:239–252
DOI: https://doi.org/10.37349/eds.2023.00016

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Review

Natural compounds from medicinal plants against COVID-19

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the coronavirus disease 2019 (COVID-19), was declared a pandemic in early 2020. During the past time, several infecti [...] Read more.

Anton Kolodnitsky ... Vladimir Poroikov

Published: August 28, 2023 Explor Drug Sci. 2023;1:253–275
DOI: https://doi.org/10.37349/eds.2023.00017
This article belongs to the special issue Exploring Potential Drugs from Natural Products

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