Biotransformation of selected secondary metabolites by Alternaria species and the pharmaceutical, food and agricultural application of biotransformation products DOI Creative Commons
Babalwa Tembeni,

Olusola Emmanuel Idowu,

Rachid Benrkia

et al.

Natural Products and Bioprospecting, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 19, 2024

Biotransformation is a process in which molecules are modified the presence of biocatalyst or enzymes, as well metabolic alterations that occur organisms from exposure to molecules. Microbial biotransformation an important natural product drug discovery novel compounds biosynthesised. Additionally, products offer with improved efficacy, solubility, reduced cytotoxic and allows for understanding structure activity relationships. One driving forces these impeccable findings associated cytochrome P450 monooxygenases present all such mammals, bacteria, fungi. Numerous fungal strains have been used reported their ability biotransform different compounds. This review focused on studies using Alternaria species biocatalysts facilitates reactions favour stereoselectivity, regioselectivity under mild conditions. microbial products, application food, pharmaceutical agricultural sector discussed this review.

Language: Английский

Metformin ameliorates doxorubicin-induced cardiotoxicity targeting HMGB1/TLR4/NLRP3 signaling pathway in mice DOI
Amany A. Alzokaky, Ahmed A. Al‐Karmalawy, Mohamed A. Saleh

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 316, P. 121390 - 121390

Published: Jan. 14, 2023

Language: Английский

Citations

24
Identification of sulphonamide-tethered N -((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease DOI Creative Commons
Mai H. ElNaggar, Abdullah A. Elgazar,

Ghada Gamal

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: July 11, 2023

SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, healthcare sectors suffered from lack effective therapeutic agents that could control spread infection. Thus, academia pharmaceutical sector prioritise antiviral drug discovery. Here, we exploited previous reports highlighting anti-SARS-CoV-2 activities isatin-based molecules develop novel triazolo-isatins for inhibiting main protease (Mpro) virus, a crucial enzyme its replication host cells. Particularly, sulphonamide 6b showed promising inhibitory activity with an IC50= 0.249 µM. Additionally, inhibited viral cell proliferation IC50 4.33 µg/ml, was non-toxic VERO-E6 cells (CC50 = 564.74 µg/ml) displaying selectivity index 130.4. In silico analysis disclosed ability interact key residues active site, supporting obtained vitro findings.

Language: Английский

Citations

18
Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N -(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies DOI Creative Commons
Ahmed A. Al‐Karmalawy, Dalia S. El‐Gamil, Rabeh El‐Shesheny

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: April 24, 2023

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt improve their biological availability and antiviral activity. Next, both cytotoxicity anti-SARS-CoV-2 activities of examined compounds loaded EMLs (F3a-g) assessed Vero E6 cells via MTT assay calculate CC50 inhibitory concentration 50 (IC50) values. The most potent 3e-loaded (F3e) elicited a selectivity index 18 with IC50 value 0.73 μg/mL. Moreover, F3e was selected for further elucidation possible mode action where results showed that it exhibited combination virucidal (>90%), viral adsorption (>80%), replication (>60%) inhibition. Besides, molecular docking MD simulations towards SARS-CoV-2 Mpro performed. Finally, structure-activity relationship (SAR) study focussed on studying influence altering size, type, flexibility α-substituent carboxamide addition compound contraction activity.HighlightsEmulsomes (3a-3g).The μg/mL against SARS-CoV-2.F3e inhibition.Molecular docking, dynamics (MD) simulations, MM-GBSA calculations performed.Structure-activity discussed

Language: Английский

Citations

14
Discovery of novel Trichoderma-based bioactive compounds for controlling potato virus Y based on molecular docking and molecular dynamics simulation techniques DOI Creative Commons
Mohamed N. Rizk, H. Ketta, Yasser M. Shabana

et al.

Chemical and Biological Technologies in Agriculture, Journal Year: 2024, Volume and Issue: 11(1)

Published: Aug. 8, 2024

Abstract Background Although potato virus Y (PVY) is the most serious virus-infecting plants worldwide, losses concurred by it remain unmanageable due to lack of efficient anti-PVY agents. Hence, objective this study was assess antiviral properties secondary metabolite compounds obtained from culture filtrates four Trichoderma spp. isolates. The assessment conducted using computational methods, including molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, as well dynamics simulations. aim develop novel effective agents for combating PVY. Results GC–MS analysis studied metabolites revealed 24 with relative amounts exceeding 10%. Molecular docking then performed MOE software evaluate activity these against PVY protein coat (PDB-ID: 6HXX). Ningnanmycin ribavirin, known plant inhibitors, were employed reference ligands comparison. Among tested, C9, C10, C13, C19 exhibited superior scores, root mean square deviation (RMSD) values, binding modes compared ligands. In addition, successfully passed ADMET analysis. Further investigation focused on C13 C19, which underwent in-depth through MDs 100 ns. trajectories demonstrated that both complexes favorable stability, compactness, throughout simulation period. However, C19/PVY-CP complex outperformed in all calculated parameters such RMSD, fluctuation (RMSF), radius gyration (RoG), solvent-accessible surface area (SASA), intermolecular hydrogen bonds. Interestingly, findings aligned results indicating C9 C10 possess high potential PVY, they like C19. Conclusion These promising outcomes provide a solid foundation considering use experimental validation studies are warranted efficacy safety their therapeutics. To our knowledge, first report biological activities -based bioactive techniques. Graphical abstract

Language: Английский

Citations

3
Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from Jasminum humile ; in silico and in Vitro assessments with structure-activity relationship DOI
Ahmed A. Al‐Karmalawy, Radwan Alnajjar, Ayman Abo Elmaaty

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(13), P. 6941 - 6953

Published: July 28, 2023

The proteolytic enzyme 3 C-like protease (3Clpro or M

Language: Английский

Citations

5
Studies on the Nonalkaloidal Secondary Metabolites of Hippeastrum vittatum (L’Her.) Herb. Bulbs DOI Creative Commons

Marwa Fathy Khalifa,

John Refaat Fahim, Ahmed E. Allam

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(30), P. 26749 - 26761

Published: July 23, 2023

Sixteen chemically varied metabolites were isolated from the bulbs of Hippeastrum vittatum (L'Her.) Herb., including eight flavonoids [3′-methyl isoliquiritigenin (2), 7-hydroxyflavan (8), 7-hydroxyflavanone (9), 7-hydroxyflavan-3-ol (10), 7-methoxy-3′,4′-methylenedioxyflavan-3-ol (11), 7-hydroxy-3′,4′-methylenedioxy flavan (12), 2′,4′-dihydroxy-3′-methyl-3,4-methylenedioxychalcone (13), and (14)], four acetophenones [2,6-dimethoxy-4-hydroxyacetophenone (3), 2,4-dihydroxyacetophenone (4), 2,4-dihydroxy-6-methoxy-3-methylacetophenone (6), 2,4,6-trimethoxyacetophenone (7)], two alkaloids [lycorine (1) narciprimine (15)], one phenol derivative [p-nitrophenol (5)], steroid [β-sitosterol 3-O-β-glucopyranoside (16)]. Their structures elucidated by combining one- two-dimensional NMR ESI-MS techniques comparison with reported literature data some authentic samples. Except for lycorine (1), obtained herein first time plants, among which compound 13 was identified as a new chalcone derivative. Additionally, total phenolic flavonoid contents ethanol extract different fractions determined Folin–Ciocalteu aluminum chloride colorimetric methods, respectively, whereas their antioxidant potential compared using phosphomolybdenum 2,2′-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. Finally, binding affinities compounds 1–16 to key target proteins severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, main protease (Mpro), papain-like (PLpro), RNA-dependent RNA polymerase (RdRp), screened molecular docking analysis. The possible chemotaxonomic significance also discussed.

Language: Английский

Citations

4
Marein Alleviates Doxorubicin-Induced Cardiotoxicity through FAK/AKT Pathway Modulation while Potentiating its Anticancer Activity DOI
Juanjuan Xu,

Manjun Lv,

Xiaohong Ni

et al.

Cardiovascular Toxicology, Journal Year: 2024, Volume and Issue: 24(8), P. 818 - 835

Published: June 19, 2024

Language: Английский

Citations

1
Exploring the therapeutic potential of Thai medicinal plants: in vitro screening and in silico docking of phytoconstituents for novel anti-SARS-CoV-2 agents DOI Creative Commons

Bussayarat Maikhunthod,

Sukanya Chaipayang, Akanitt Jittmittraphap

et al.

BMC Complementary Medicine and Therapies, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 19, 2024

The high virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for disease 2019 (COVID-19), has triggered global health and economic concerns. absence specific antiviral treatments the side effects repurposed drugs present persistent challenges. This study explored a promising herbal extract against SARS-CoV-2 from selected Thai medicinal plants based on in vitro efficacy evaluated its lead compounds by molecular docking.

Language: Английский

Citations

1
Identification of Antimicrobial Metabolites from the Egyptian Soil-Derived Amycolatopsis keratiniphila Revealed by Untargeted Metabolomics and Molecular Docking DOI Creative Commons

Ahmed A. Hamed,

Osama G. Mohamed, Somayah S. Elsayed

et al.

Metabolites, Journal Year: 2023, Volume and Issue: 13(5), P. 620 - 620

Published: April 30, 2023

Actinomycetes are prolific producers of bioactive secondary metabolites. The prevalence multidrug-resistant (MDR) pathogens has prompted us to search for potential natural antimicrobial agents. Herein, we report the isolation rare actinobacteria from Egyptian soil. strain was identified as Amycolatopsis keratiniphila DPA04 using 16S rRNA gene sequencing. Cultivation profiling, followed by chemical and evaluation crude extracts, revealed activity ISP-2 M1 culture extracts against Gram-positive bacteria. Minimum inhibitory concentrations (MIC) values ranged 19.5 39 µg/mL. Chemical analysis ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) led identification 45 metabolites different classes. In addition, ECO-0501 in cultures with significant activity. Multidrug resistance Staphylococcus aureus is reported be related multidrug efflux pump (MATE). its were subjected molecular docking studies MATE receptor a proposed mechanism action. derivatives (AK_1 N-demethyl ECO-0501) had better binding scores (−12.93, −12.24, −11.92 kcal/mol) than co-crystallized 4HY inhibitor (−8.99 making them promising candidates inhibitors. Finally, our work established that products this could useful therapeutic tools controlling infectious diseases.

Language: Английский

Citations

3
An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery DOI
Mahmoud Kandeel

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(4), P. 385 - 400

Published: March 27, 2023

Introduction The Middle East respiratory syndrome coronavirus (MERS-CoV) has remained a public health concern since it first emerged in 2012. Although many potential treatments for MERS-CoV have been developed and tested, none had complete success stopping the spread of this deadly disease. replication comprises attachment, entry, fusion steps. Targeting these events may lead to creation medications that effectively treat infection.Areas covered This review updates research on development inhibitors MERS-CoV. main topics are MERS-CoV‒related proteins host cell involved viral protein activation infection.Expert opinion Research discovering drugs can inhibit started at slow pace, although efforts steadily increased, clinical trials new specifically targeting not extensive enough. explosion find SARS-CoV-2 virus indirectly enhanced volume data inhibition by including drug assays. appearance COVID-19 completely transformed available inhibition. Despite fact infected cases constantly being diagnosed, there currently no approved vaccines or

Language: Английский

Citations

2