Chemical Composition of the Red Sea Green Algae Ulva lactuca: Isolation and In Silico Studies of New Anti-COVID-19 Ceramides

Coronavirus disease 2019 (COVID-19) is the disease caused by the virus SARS-CoV-2 responsible for the ongoing pandemic which has claimed the lives of millions of people. This has prompted the scientific research community to act to find treatments against the SARS-CoV-2 virus that include safe antiviral medicinal compounds. The edible green algae U. lactuca. is known to exhibit diverse biological activities such as anti-influenza virus, anti-Japanese encephalitis virus, immunomodulatory, anticoagulant, antioxidant and antibacterial activities. Herein, four new ceramides in addition to two known ones were isolated from Ulva lactuca. The isolated ceramides, including Cer-1, Cer-2, Cer-3, Cer-4, Cer-5 and Cer-6 showed promising antiviral activity against SARS-CoV-2 when investigated using in silico approaches by preventing its attachment to human cells and/or inhibiting its viral replication. Cer-4 and Cer-5 were the most effective in inhibiting the human angiotensin converting enzyme (hACE)–spike protein complex which is essential for the virus to enter the human host. In addition to this, Cer-4 also showed an inhibition of the SARS-CoV-2 protease (Mpro) that is responsible for its viral replication and transcription. In this study, we also used liquid chromatography coupled to electrospray ionization high-resolution mass spectroscopy (LC–ESI–HRMS) to identify several metabolites of U. lactuca, including metabolites such as fatty acids, their glyceride derivatives, terpenoids, sterols and oxysterols from the organic extract. Some of these metabolites also possessed promising antiviral activity, as previously reported.

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Chalcones: As potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies

Medicinal Chemistry ◽

10.2174/1573406416666200611103039 ◽

2020 ◽

Vol 16 ◽

Author(s):

Mahboob Ali ◽

Momin Khan ◽

Khair Zaman ◽

Abdul Wadood ◽

Maryam Iqbal ◽

...

Keyword(s):

In Silico ◽

Enzyme Inhibitors ◽

Biological Activities ◽

Condensation Reaction ◽

Type Ii Diabetes Mellitus ◽

Spectroscopic Techniques ◽

Chalcone Derivatives ◽

In Silico Studies ◽

Wide Range

: Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-17) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Method: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by ClaisenSchmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-17) were synthesized, characterized, and evaluated for their α-amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

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In silico screening of pyridoxine carbamates for Anti-Alzheimer’s activities

Central Nervous System Agents in Medicinal Chemistry ◽

10.2174/1871524920666201119144535 ◽

2020 ◽

Vol 20 ◽

Author(s):

Dnyaneshwar Baswar ◽

Abha Sharma ◽

Awanish Mishra

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

In Silico ◽

Neurodegenerative Disorder ◽

Biological Activities ◽

Cholinergic Neurons ◽

In Silico Screening ◽

In Silico Studies ◽

Bbb Permeability ◽

Ld50 Value

Background: Alzheimer’s disease (AD), an irreversible complex neurodegenerative disorder, is most common type of dementia, with progressive loss of cholinergic neurons. Based on the multi- factorial etiology of Alzheimer’s disease, novel ligands strategy appears as up-coming approach for the development of newer molecules against AD. This study is envisaged to investigate anti-Alzheimer’s potential of 10 synthesized compounds. The screening of compounds (1-10) was carried out using in silico techniques. Methods: For in silico screening of physicochemical properties of compounds molinspiration property engine v.2018.03, Swiss ADME online web-server and pkCSM ADME were used. For pharmacodynamic prediction PASS software while toxicity profile of compounds were analyzed through ProTox-II online software. Simultaneously, molecular docking analysis was performed on mouse AChE enzyme (PDB ID:2JGE, obtained from RSCB PDB) using Auto Dock Tools 1.5.6. Results: Based on in silico studies, compound 9 and 10 have been found to have better drug likeness, LD50 value, and better anti-Alzheimer’s, nootropic activities. However, these compounds had poor blood brain barrier (BBB) permeability. Compound 4 and 9 were predicted with better docking score for AChE enzyme. Conclusion: The outcome of in silico studies have suggested, out of various substitutions at different positions of pyridoxine-carbamate, compound 9 have shown promising drug likeness, with better safety and efficacy profile for anti-Alzheimer’s activity. However, BBB permeability appears as one the major limitation of all these compounds. Further studies are required to confirm its biological activities.

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Screening and Purification of NanB Sialidase From Pasteurella Multocida With Activity in Hydrolyzing Sialic Acid Neu5Acα(2-6)Gal

10.21203/rs.3.rs-810816/v2 ◽

2021 ◽

Author(s):

Christian Marco Hadi Nugroho ◽

Ryan Septa Kurnia ◽

Simson Tarigan ◽

Otto Sahat Martua Silaen ◽

Silvia Tri Widyaningtyas ◽

...

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Red Blood Cells ◽

Blood Cells ◽

In Silico ◽

Pasteurella Multocida ◽

Antiviral Agents ◽

Influenza Virus Infection ◽

Ligand Complex ◽

In Silico Studies

Abstract Study on sialidases as antiviral agents has been widely performed, but many types of sialidase had not been tested for their antiviral activity. One of such sialidase is the NanB sialidase of Pasteurella multocida, which has never been isolated for further study. In this study, the activity of NanB sialidase was investigated in silico by docking the NanB sialidase of Pasteurella multocida to the Neu5Acα(2-6)Gal ligand. Additionally, some local isolates of Pasteurella multocida, which had the NanB gene were screened, and the proteins were isolated for further testing regarding their activity in hydrolyzing Neu5Acα(2-6)Gal. In silico studies showed that the NanB sialidase possesses an exceptional affinity towards forming a protein-ligand complex with Neu5Acα(2-6)Gal. This was further confirmed by showing that a dose of 0.258 U/ml (100%) NanB sialidase of Pasteurella multocida B018 can hydrolyze up to 44.28% of Neu5Acα(2-6)Gal in chicken red blood cells and 81.95% in rabbit red blood cells. This study suggested that the NanB sialidase of Pasteurella multocida B018 has a potent antiviral activity that can inhibit avian influenza virus infection.

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Tangeretin and its Derivatives: An Integrative Bioinformatic Study of Obesity and Related Immunodeficiency

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i50b33448 ◽

2021 ◽

pp. 247-266

Author(s):

V. Manjunath ◽

Kaveripakam Sai Sruthi ◽

Sreedevi Adikay

Keyword(s):

Immune Deficiency ◽

In Silico ◽

Nadh Oxidase ◽

Biological Activities ◽

Docking Studies ◽

Ligand Docking ◽

Health Concern ◽

Obese People ◽

In Silico Studies ◽

Electronic Parameters

Obesity is a complex and major public health concern known to exacerbate many diseases. There are increasing evidences stating the obese people due to adiposity are getting more susceptible to immune deficiency disorders. Tangeretin is a key member of flavonoids reported to have many favourable biological activities. In search of novel leads in ameliorating obesity and related immunodeficiency, the present study is aimed at the in silico evaluation of tangeretin derivatives to assess their biological role. Initially tangeretin derivatives are designed by molecular manipulation approach.Drug likeness and bioactivity score prediction was done using Molinspiration web tool. Swiss ADME prediction and toxicological predictions were performed. In silico Molecular Docking studies were performed by employing a flexible ligand docking approach using Schrodinger on the protein targets namely leptin, Fat mass and obesity associated protein (FTO), Pancreatic lipase, Peroxisome proliferated receptor (PPARɣ) and NADH oxidase. Further the electronic parameters were computed for the best fitted ligands by DFT analysis. The evaluation of results was made based on Glide (Schrodinger) dock score. Out of 18 screened compounds, some of them showed the best docking scores with the targets when compared with the standard (Lovastatin). Particularly the two ligands (L-13 and L-8) showed the best binding score with all five targets. Moreover, DFT analysis carried out for the tangeretin and best fitted ligands (L13 and L8) substantiated the other in silico studies. These findings probably provide excellent lead candidates for the development of therapeutic drugs in combating obesity and related immune deficiency.

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Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes

Medicinal Chemistry ◽

10.2174/1573406417666210216154428 ◽

2021 ◽

Vol 17 ◽

Author(s):

Thiago M. de Aquino ◽

Paulo H. B. França ◽

Érica E. E. S. Rodrigues ◽

Igor J. S. Nascimento ◽

Paulo F. S. Santos-Júnior ◽

...

Keyword(s):

In Silico ◽

Biological Activities ◽

Leishmania Species ◽

Antileishmanial Activity ◽

Trypanothione Reductase ◽

Aromatic Substituent ◽

In Silico Studies ◽

Ic50 Values ◽

The Impact

Background: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. Objective: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds. Method: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software. Result: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. Conclusion: The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

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New Cell Cycle Checkpoint Pathways Regulators with 2-Oxo-indoline Scaffold as Potential Anticancer Agents: Design, Synthesis, Biological Activities and In Silico Studies

Bioorganic Chemistry ◽

10.1016/j.bioorg.2022.105622 ◽

2022 ◽

pp. 105622

Author(s):

Hend A.A. Abd El-wahab ◽

Hany S. Mansour ◽

Ahmed M. Ali ◽

Raafat El-Awady ◽

Tarek Aboul-Fadl

Keyword(s):

Cell Cycle ◽

Anticancer Agents ◽

In Silico ◽

Biological Activities ◽

Cell Cycle Checkpoint ◽

Design Synthesis ◽

In Silico Studies ◽

Cycle Checkpoint

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Cytotoxicity, Antimicrobial, and In Silico Studies of Secondary Metabolites From Aspergillus sp. Isolated From Tecoma stans (L.) Juss. Ex Kunth Leaves

Frontiers in Chemistry ◽

10.3389/fchem.2021.760083 ◽

2021 ◽

Vol 9 ◽

Author(s):

Heba E. Elsayed ◽

Reem A. Kamel ◽

Reham R. Ibrahim ◽

Ahmed S. Abdel-Razek ◽

Mohamed A. Shaaban ◽

...

Keyword(s):

Secondary Metabolites ◽

In Silico ◽

Therapeutic Potential ◽

Antibacterial Activities ◽

Antimicrobial Activities ◽

Kinase Domain ◽

Binding Score ◽

In Silico Studies ◽

Binding Cleft ◽

Aspergillus Sp

Endophytes are prolific producers of privileged secondary metabolites with diverse therapeutic potential, although their anticancer and antimicrobial potential still have a room for further investigation. Herein, seven known secondary metabolites namely, arugosin C (1), ergosterol (2), iso-emericellin (3), sterigmatocystin (4), dihydrosterigmatocystin (5), versicolorin B (6), and diorcinol (7) were isolated from the rice culture of Aspergillus sp. retrieved from Tecoma stans (L.) Juss. ex Kunth leaves. Their anticancer and antimicrobial activities were evaluated in MTT and agar well diffusion assays, respectively. The cytotoxicity results showed that metabolite 3 displayed the best viability inhibition on the MCF-7 breast cancer cells with IC50 = 225.21 µM, while 5 on the HepG2 hepatocellular carcinoma cells with IC50 = 161.81 µM. 5 demonstrated a 60% apoptotic mode of cell death which is virtually correlated to its high docking affinity to Hsp90 ATP binding cleft (binding score −8.4 Kcal/mol). On the other side, metabolites 4 and 5 displayed promising antimicrobial activity especially on Pseudomonas aeruginosa with MIC = 125 μg/ml. The observed effect may be likely related to their excellent in silico inhibition of the bacterial DNA-gyrase kinase domain (binding score −10.28 Kcal/mol). To the best of our knowledge, this study is the first to report the promising cytotoxic and antibacterial activities of metabolites 3, 4, and 5 which needs further investigation and renovation to therapeutic leads.

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Computer-Based Approaches for Determining the Pharmacological Profile of 5-(3-Nitro-Arylidene)-Thiazolidine-2,4-Dione

Biointerface Research in Applied Chemistry ◽

10.33263/briac116.1380613828 ◽

2021 ◽

Vol 11 (6) ◽

pp. 13806-13828

Keyword(s):

Molecular Docking ◽

In Silico ◽

Density Functional ◽

Biological Activities ◽

Computational Approach ◽

Basis Set ◽

Pharmacological Profile ◽

Dft Methods ◽

Starting Point ◽

In Silico Studies

The development of novel and safe compounds is a challenging task in the drug discovery trajectory. Accordingly, the individuation of promising core molecules with biological activities could pave the way to develop effective drugs to treat a given disease. The use of a computational approach can reduce the time for identifying promising core molecules characterizing their potential pharmacological profile and providing hints for the synthesis of novel derivatives with increased predicted pharmacological activity. Following this strategy, starting from a core molecule thiazolidine-2,4-dione, the derivative of 5-(3-nitro-arylidene)-thiazolidine-2,4-dione was synthesized to investigate the biological and pharmacological potential. An extensive computational investigation was performed employing ab initio calculations by using Density Functional Theory (DFT), and subsequent in silico studies were accomplished by molecular docking calculation. The structures 5-(3-nitro-arylidene)-thiazolidine-2,4-dione were fully optimized using multiparametric DFT methods were calculated at the B3LYP/6-31+G (d, p) level basis set. Besides gaining insights into the potential pharmacological profile of the selected derivative, molecular docking against some selected drug targets, ADME, and PASS prediction were performed. According to charges and molecular electrostatic potential (MESP) calculation, the N-H region could offer promising active site interactions for protein binding. Furthermore, Homo-Lumo and global reactivity values indicate a good profile for the selected compound, and UV-Vis provides further insights about its properties, potentially helpful for further experimental analysis. Notably, the in silico investigation indicated that EGFR and ORF2 enzymes could represent the selected drug-like compound's possible targets. Conclusively, the proposed computational approach demonstrated that it is possible to evaluate a proposed compound's bioactivity profile. We characterized 5-(3-nitro-arylidene)-thiazolidine-2,4-dione derivative, suggesting it as a good starting point for developing interesting hit compounds with a relevant pharmacological profile.

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Screening and Purification of NanB Sialidase from Pasteurella Multocida with Activity in Hydrolyzing Sialic Acid Neu5Acα(2-6)Gal

10.21203/rs.3.rs-810816/v1 ◽

2021 ◽

Author(s):

Christian Marco Hadi Nugroho ◽

Ryan Septa Kurnia ◽

Simson Tarigan ◽

Otto Sahat Martua Silaen ◽

Silvia Tri Widyaningtyas ◽

...

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Red Blood Cells ◽

Blood Cells ◽

In Silico ◽

Pasteurella Multocida ◽

Antiviral Agents ◽

Influenza Virus Infection ◽

Ligand Complex ◽

In Silico Studies

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Unveiling Pharmacological Responses and Potential Targets Insights of Identified Bioactive Constituents of Cuscuta reflexa Roxb. Leaves through In Vivo and In Silico Approaches

Pharmaceuticals ◽

10.3390/ph13030050 ◽

2020 ◽

Vol 13 (3) ◽

pp. 50 ◽

Cited By ~ 9

Author(s):

Md. Adnan ◽

Md. Nazim Uddin Chy ◽

A.T.M. Mostafa Kamal ◽

Md. Riad Chowdhury ◽

Md. Shariful Islam ◽

...

Keyword(s):

Acetic Acid ◽

In Silico ◽

Serotonin Receptor ◽

Biological Activities ◽

Indigenous Communities ◽

Bioactive Constituents ◽

Cuscuta Reflexa ◽

In Silico Studies ◽

Dose Dependent

Cuscuta reflexa Roxb. is traditionally used by the indigenous communities of Bangladesh to treat different diseases, such as pain, edema, tumor, jaundice, and skin infections. This study tested neuro-pharmacological, anti-nociceptive, and antidiarrheal activities by in vivo and in silico experiments for the metabolites extracted (methanol) from the leaves of Cuscuta reflexa (MECR). During the anxiolytic evaluation analyzed by elevated plus maze and hole board tests, MECR (200 and 400 mg/kg) exhibited a significant dose-dependent reduction of anxiety-like behavior in mice. Similarly, mice treated with MECR demonstrated a dose-dependent decrease in the time of immobility in both forced swimming and tail suspension tests. In addition, anti-nociceptive activity was assessed by the chemical-induced (acetic acid and formalin) pain models. In both cases, 400 mg/kg was found to be most effective and significantly (p < 0.001) inhibited acetic acid stimulated writhing and formalin-induced licking (pain response) in mice. Furthermore, antidiarrheal efficacy determined by the castor-oil induced diarrheal model manifested an evident inhibition of diarrheal stool frequency. In parallel, previously isolated bioactive compounds were documented based on the biological activities and subjected to in silico studies to correlate with the current pharmacological outcomes. The selected isolated compounds (15) displayed favorable binding affinities to potassium channels, human serotonin receptor, COX-1, COX-2, M3 muscarinic acetylcholine receptor, and 5-HT3 receptor proteins. Additionally, the ADME/T and toxicological properties were justified to unveil their drug-like properties and toxicity level. Overall, Cuscuta reflexa is bioactive and could be a potential source for the development of alternative medicine.

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