Discovery of Novel Tryptanthrin Derivatives with Benzenesulfonamide Substituents as Multi-Target-Directed Ligands for the Treatment of Alzheimer’s Disease

Pharmaceuticals, Год журнала: 2023, Номер 16(10), С. 1468 - 1468

Опубликована: Окт. 16, 2023

Based on the multi-target-directed ligands (MTDLs) approach, two series of tryptanthrin derivatives with benzenesulfonamide substituents were evaluated as multifunctional agents for treatment Alzheimer’s disease (AD). In vitro biological assays indicated most had good cholinesterase inhibitory activity and neuroprotective properties. Among them, target compound 4h was considered a mixed reversible dual inhibitor acetylcholinesterase (AChE, IC50 = 0.13 ± 0.04 μM) butyrylcholinesterase (BuChE, 6.11 0.15 μM). And it could also potentially prevent generation amyloid plaques by inhibiting self-induced Aβ aggregation (63.16 2.33%). Molecular docking studies used to explore interactions AChE, BuChE, Aβ. Furthermore, possessing significant anti-neuroinflammatory potency (NO, IL-1β, TNF-α; 0.62 0.07 μM, 1.78 0.21 1.31 0.28 respectively) reduced ROS production, chelated biometals found in 4h. Further showed that proper blood–brain barrier (BBB) permeability suitable metabolic stability. vivo study, effectively ameliorated learning memory impairment scopolamine-induced AD mice model. These findings suggested may be promising further development agent AD.

Язык: Английский

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Diosgenin as a Novel Therapeutic Natural Product for Various Diseases: An Overview

Journal of Natural Remedies, Год журнала: 2023, Номер unknown, С. 339 - 350

Опубликована: Июнь 13, 2023

Diosgenin (DG) is a saponin glycoside and an active constituent generally present in medicinal plants like Rhizoma polgonita, Trigonella foenum, Dioscorea villosa rhizome. It also the starting material for biosynthesis of steroidal hormones. DG has been reported as multipurpose drug aiding treatment various cardiovascular, neurological diseases well malignancies, osteoporosis, diabetes, atherosclerosis. The underlying mechanisms contributing towards potential therapeutic ability to suppress expression oncogenic genes, preventing formation free radicals thereby resulting neuroprotection etc. However, use restricted due its limited pharmacokinetic properties such poor aqueous solubility, bioavailability, quicker biotransformation into metabolites. Hence, this study we have briefed current approaches derivatives alongside chemistry physicochemical, pharmacological & toxicological properties.

Язык: Английский

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Synthesis, Structural Analysis and Antiproliferative Activity of Nitrogen‐Containing Hetero Spirostan Derivatives: Oximes, Heterocyclic Ring‐Fused and Furostanes

ChemistrySelect, Год журнала: 2022, Номер 7(24)

Опубликована: Июнь 21, 2022

Abstract The present study focuses on the synthesis of spirostan derivatives as potential drug candidates for biological applications. Recently, containing hetero‐atom have attracted great scientific attention due to their anti‐cancer, anti‐diabetes, and anti‐inflammatory properties. In this study, nitrogen‐containing novel with substituted oxime, nitrile, pyrazole, isoxazole structures in ring‐A F were designed synthesized starting from diosgenin. intermediates target derivatives’ chemical characterized by FTIR, HRMS, 1 HNMR, 13 CNMR, elemental analysis, HPLC techniques. compounds evaluated cytotoxicities two human cancer cell lines (MCF‐7 A549). tested exhibited potent anticancer activity against breast adenocarcinoma (MCF‐7) lung (A549). On other hand, toxicity healthy fetal fibroblasts (MCR‐5) indicated that non‐toxic body. results showed may be used a promising agents improved efficacy.

Язык: Английский

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Diosgenin derivatives developed from Pd(ii) catalysed dehydrogenative coupling exert an effect on breast cancer cells by abrogating their growth and facilitating apoptosis via regulating the AKT1 pathway

Dalton Transactions, Год журнала: 2022, Номер 51(17), С. 6766 - 6777

Опубликована: Янв. 1, 2022

Palladium metallates containing 4-oxo-4H-chromene-3-carbaldehyde derived ONS donor Schiff bases were synthesized and their efficacy was tested in the direct amination of diosgenin - a phyto steroid. Based on pharmacological importance diosgenin, obtained derivatives exposed to study effect breast cancer cells where they significantly reduced growth left non-malignant epithelial unaffected. Among derivatives, D3, D4 D6 showed better anti-proliferative further analysis revealed that markedly promoted cell cycle arrest apoptosis by attenuation AKT1 signalling pathway.

Язык: Английский

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Synthesis of fully functionalized spirostanic 1,2,3-triazoles by the three component reaction of diosgenin azides with acetophenones and aryl aldehydes and their biological evaluation as antiproliferative agents

Steroids, Год журнала: 2022, Номер 190, С. 109133 - 109133

Опубликована: Окт. 31, 2022

Язык: Английский

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