Anticholinesterase Activity of Budmunchiamine Alkaloids Revealed by Comparative Chemical Profiling of Two Albizia spp., Molecular Docking and Dynamic Studies DOI Creative Commons
Mai Hussein, Osama G. Mohamed, Ahlam M. El-Fishawy

et al.

Plants, Journal Year: 2022, Volume and Issue: 11(23), P. 3286 - 3286

Published: Nov. 29, 2022

Alzheimer’s disease remains a global health challenge and an unmet need requiring innovative approaches to discover new drugs. The current study aimed investigate the inhibitory activity of Albizia lucidior procera leaves against acetylcholinesterase enzyme in vitro explore their chemical compositions. Metabolic profiling bioactive plant, A. lucidior, via UHPLC/MS/MS-based Molecular Networking highlighted richness its ethanolic extract with budmunchiamine alkaloids, fourteen alkaloids as well four putative ones were tentatively identified for first time lucidior. Pursuing these fractions molecular networking revealed that mainly concentrated ethyl acetate fraction. In agreement, alkaloid-rich fraction showed most promising anticholinesterase (IC50 5.26 µg/mL) versus 24.89 6.90 µg/mL, respectively), compared donepezil 3.90 µg/mL). Furthermore, deep silico studies performed. Notably, normethyl K superior stability receptor binding affinity two used references: co-crystallized inhibitor (MF2 700). This was concluded based on docking, dynamics simulations mechanics generalized born/solvent accessibility (MM–GBSA) calculations.

Language: Английский

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
Synergistic effects of steric constraints and non-covalent interactions in copper(ii) chloro-nitro-benzoato complexes: synthesis, structural characterization, theoretical investigations, antimicrobial studies, and molecular docking analyses DOI
Chetan Chauhan, Santosh Kumar,

Rajesh Kumar

et al.

New Journal of Chemistry, Journal Year: 2024, Volume and Issue: 48(9), P. 3829 - 3848

Published: Jan. 1, 2024

Design, synthesis, detailed structural characterization and potential biological efficacy of copper( ii ) chloro-benzoato complexes displaying the synergistic role steric constraints non-covalent interactions have been carried out for first time.

Language: Английский

Citations

5
Multi-target rational design and synthesis of novel diphenyl-tethered pyrazolopyrimidines targeting EGFR and topoisomerase II with potential DNA intercalation and apoptosis induction DOI

Ahmed A. Abdel Gaber,

Ayman Abo Elmaaty, Marwa Sharaky

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 145, P. 107223 - 107223

Published: Feb. 17, 2024

Language: Английский

Citations

5
Recent advances in small-molecular therapeutics for COVID-19 DOI Creative Commons
Lei Zhong, Zhipeng Zhao,

Xuerun Peng

et al.

Precision Clinical Medicine, Journal Year: 2022, Volume and Issue: 5(4)

Published: Sept. 24, 2022

Abstract The COVID-19 pandemic poses a fundamental challenge to global health. Since the outbreak of SARS-CoV-2, great efforts have been made identify antiviral strategies and develop therapeutic drugs combat disease. There are different for developing small molecular anti-SARS-CoV-2 drugs, including targeting coronavirus structural proteins (e.g. spike protein), non-structural (nsp) RdRp, Mpro, PLpro, helicase, nsp14, nsp16), host proteases TMPRSS2, cathepsin, furin) pivotal mediating endocytosis PIKfyve), as well endosome acidification agents immune response modulators. Favipiravir chloroquine that were identified earlier in this epidemic repurposed clinical therapy based on these strategies. However, their efficacies controversial. Currently, three agents, remdesivir, molnupiravir, Paxlovid (PF-07321332 plus ritonavir), granted emergency use authorization or approved many countries due significant curative effects phase III trials. Meanwhile, large number promising drug candidates entered evaluation. development brings hope us finally conquer COVID-19. In account, we conducted comprehensive review recent advances molecule according target classification. Here present all most important each target, discuss challenges perspectives future research drugs.

Language: Английский

Citations

21
Anticholinesterase Activity of Budmunchiamine Alkaloids Revealed by Comparative Chemical Profiling of Two Albizia spp., Molecular Docking and Dynamic Studies DOI Creative Commons
Mai Hussein, Osama G. Mohamed, Ahlam M. El-Fishawy

et al.

Plants, Journal Year: 2022, Volume and Issue: 11(23), P. 3286 - 3286

Published: Nov. 29, 2022

Alzheimer’s disease remains a global health challenge and an unmet need requiring innovative approaches to discover new drugs. The current study aimed investigate the inhibitory activity of Albizia lucidior procera leaves against acetylcholinesterase enzyme in vitro explore their chemical compositions. Metabolic profiling bioactive plant, A. lucidior, via UHPLC/MS/MS-based Molecular Networking highlighted richness its ethanolic extract with budmunchiamine alkaloids, fourteen alkaloids as well four putative ones were tentatively identified for first time lucidior. Pursuing these fractions molecular networking revealed that mainly concentrated ethyl acetate fraction. In agreement, alkaloid-rich fraction showed most promising anticholinesterase (IC50 5.26 µg/mL) versus 24.89 6.90 µg/mL, respectively), compared donepezil 3.90 µg/mL). Furthermore, deep silico studies performed. Notably, normethyl K superior stability receptor binding affinity two used references: co-crystallized inhibitor (MF2 700). This was concluded based on docking, dynamics simulations mechanics generalized born/solvent accessibility (MM–GBSA) calculations.

Language: Английский

Citations

19