Design, synthesis, and biological evaluation of thienopyrimidine derivatives as multifunctional agents against Alzheimer's disease

Drug Development Research, Journal Year: 2023, Volume and Issue: 84(5), P. 937 - 961

Published: April 17, 2023

A series of 12 S-substituted tetrahydrobenzothienopyrimidines were designed and synthesized based on the donepezil scaffold. All newly compounds evaluated for their acetylcholinesterase (AChE) inhibitory activity most active tested butyrylcholinesterase (BuChE) activity. Moreover, all effects against Aβ aggregation antioxidant using oxygen radical absorbance capacity method. Compounds 4b, 6b, 8b displayed prominent AChE action comparable to donepezil. Compound 6b showed greatest (IC50 = 0.07 ± 0.003 µM) potent BuChE 0.059 0.004 µM). Furthermore, three exhibited significant exerted more than The cytotoxic WI-38 cell line in comparison with was examined 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. results revealed that less cytotixic donepezil, while compound 4b nonsignificant cytotoxicity compared For insights about binding patterns promising (4b, 8b) at molecular levels; docking dynamics simulations performed. density functional theory calculations absorption, distribution, metabolism, excretion toxicity properties described as well. highlighted which incorporates a phenylpiperazine moiety coupled thienopyrimidone scaffold via two-atom spacer, be multifunctional therapeutic agent treatment Alzheimer's disease. It is dual inhibitor. it had stronger Additionally,

Language: Английский

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Anti-Entry Activity of Natural Flavonoids against SARS-CoV-2 by Targeting Spike RBD

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 160 - 160

Published: Jan. 4, 2023

COVID-19 is still a global public health concern, and the SARS-CoV-2 mutations require more effective antiviral agents. In this study, entry activity of thirty-one flavonoids was systematically evaluated by pseudovirus model. Twenty-four exhibited with IC50 values ranging from 10.27 to 172.63 µM SI 2.33 48.69. The structure-activity relationship these as inhibitors comprehensively summarized. A subsequent biolayer interferometry assay indicated that bind viral spike RBD block interaction ACE2 receptor, molecular docking study also revealed flavonols could Pocket 3, non-mutant regions variants, suggesting might be active against virus variants. These natural showed very low cytotoxic effects on human normal cell lines. Our findings suggested potential agents via inactivating spike. It hoped our will provide some encouraging evidence for use disinfectants prevent infections.

Language: Английский

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Investigation of the phytochemical composition, antioxidant, antibacterial, anti-osteoarthritis, and wound healing activities of selected vegetable waste

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 10, 2023

Abstract Agri-food wastes, produced following industrial food processing, are mostly discarded, leading to environmental hazards and losing the nutritional medicinal values associated with their bioactive constituents. In this study, we performed a comprehensive analytical biological evaluation of selected vegetable by-products (potato, onion, garlic peels). The phytochemical analysis included UHPLC-ESI-qTOF-MS/MS in combination molecular networking determination total flavonoid phenolic contents. Further, antimicrobial, anti-osteoarthritis wound healing potentials were also evaluated. total, 47 compounds identified, belonging acids, flavonoids, saponins, alkaloids as representative chemical classes. Onion peel extract (OPE) showed higher polyphenolic contents, promising antioxidant activity, potential antimicrobial especially against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, OPE revealed have vivo restoring tissue physiology integrity, mainly through activation AP-1 signaling pathway. Lastly, when was loaded nanocapsule based hydrogel, nano-formulation enhanced cellular viability. affinities major metabolites evaluated both p65 ATF-2 targets using two different docking processes revealing quercetin-3,4′- O -diglucoside, alliospiroside C, D most entities superior binding scores. These results demonstrate that by-products, particularly, those derived from onion peels can be incorporated natural by-product for future wounds osteoarthritis.

Language: Английский

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Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview

Vaccines, Journal Year: 2021, Volume and Issue: 9(11), P. 1317 - 1317

Published: Nov. 12, 2021

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus cause of disease 2019 (COVID-19), mild-to-severe tract infection frequent ability to give rise fatal pneumonia humans. The overwhelming outbreak SARS-CoV-2 continues unfold all over world, urging scientists put an end this global pandemic through biological and pharmaceutical interventions. there no specific treatment option that capable COVID-19 eradication, so several repurposed drugs conditionally approved vaccines use heavily applied control pandemic. emergence variants partially or totally escape immune response elicited by requires continuous monitoring update content developed modify them match variants. Herein, we discuss potential therapeutic prophylactic interventions including developed/approved vaccines, highlighting impact evolution on evasion currently licensed for COVID-19.

Language: Английский

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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

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

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