4- Substituted sampangine derivatives: Novel acetylcholinesterase and β-myloid aggregation inhibitors

Chen, Kelin; Gan, Lu; Wu, Zhenhua; Qin, Jin-Fang; Liao, Wenxia; Tang, Huang

doi:10.1016/j.ijbiomac.2017.10.157

Cited by 7 publications

(2 citation statements)

References 37 publications

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“…Inspired by the molecular backbone of Sampangine, Jiang et al designed new analogs as antifungal lead compounds with facile synthesis, low toxicity, and strong inhibitory effects on fungal biofilms [19]. Chen et al found that a simplified sampangine derivative has the ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-myeloid (Aβ) aggregation with increased water solubility and reduced toxicity [20].…”

Section: Introductionmentioning

confidence: 99%

Scaffold Hopping and Structural Modification of NSC 663284: Discovery of Potent (Non)Halogenated Aminobenzoquinones

Bayrak,

Sever,

Ciftci

et al. 2023

Biomedicines

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The development of new anticancer drugs is still ongoing as a solution to the unsatisfactory results obtained by chemotherapy patients. Our previous studies on natural product-based anticancer agents led us to synthesize a new series of Plastoquinone (PQ) analogs and study their anticancer effects. Four members of PQ analogs (PQ1–4) were designed based on the scaffold hopping strategy; the design was later completed with structural modification. The obtained PQ analogs were synthesized and biologically evaluated against different cancer genotypes according to NCI-60 screening in vitro. According to the NCI results, bromo and iodo-substituted PQ analogs (PQ2 and PQ3) showed remarkable anticancer activities with a wide-spectrum profile. Among the two selected analogs (PQ2 and PQ3), PQ2 showed promising anticancer activity, in particular against leukemia cell lines, at both single- and five-dose NCI screenings. This compound was also detected by MTT assay to reveal significant selectivity between Jurkat cells and PBMC (healthy) compared to imatinib. Further in silico studies indicated that PQ2 was able to occupy the ATP-binding cleft of Abl TK, one of the main targets of leukemia, through key interactions similar to dasatinib and imatinib. PQ2 is also bound to the minor groove of the double helix of DNA. Based on computational pharmacokinetic studies, PQ2 possessed a remarkable drug-like profile, making it a potential anti-leukemia drug candidate for future studies.

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Section: Introductionmentioning

confidence: 99%

Scaffold Hopping and Structural Modification of NSC 663284: Discovery of Potent (Non)Halogenated Aminobenzoquinones

Bayrak,

Sever,

Ciftci

et al. 2023

Biomedicines

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“…However, severe toxicity associated with the organophosphates, which occasionally lead to death, impede their clinical applications in AD. − Thus, exploration of new chemical scaffolds with reduced toxicity is still an active area of research. Recently, astaxanthin- s -allyl cysteine, a sampangine derivative, eugenol derivatives, acridine-coumarin hybrids, and flavonoids , have been shown to inhibit cholinesterases. The present work aims to identify novel selective AChEIs using a combination of structure- and ligand-based approaches.…”

Section: Introductionmentioning

confidence: 99%

Combined Structure and Ligand-Based Design of Selective Acetylcholinesterase Inhibitors

Pérez‐Sánchez

Haan

Pérez‐Garrido

et al. 2020

J. Chem. Inf. Model.

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Acetylcholinesterase is a prime target for therapeutic intervention in Alzheimer's disease. Acetylcholinesterase inhibitors (AChEIs) are used to improve cognitive abilities, playing therefore an important role in disease management. Drug repurposing screening has been performed on a corporate chemical library containing 11 353 compounds using a target fishing approach comprising three-dimensional (3D) shape similarity and pharmacophore modeling against an approved drug database, Drugbank. This initial screening identified 108 hits. Among them, eight molecules showed structural similarity to the known AChEI drug, pyridostigmine. Further structure-based screening using a pharmacophore-guided rescoring method identifies one more potential hit. Experimental evaluations of the identified hits sieve out a highly selective AChEI scaffold. Further lead optimization using a substructure search approach identifies 24 new potential hits. Three of the 24 compounds (compounds 10b, 10h, and 10i) based on a 6-(2-(pyrrolidin-1-yl)pyrimidin-4-yl)-thiazolo[3,2-a]pyrimidine scaffold showed highly promising AChE inhibition ability with IC 50 values of 13.10 ± 0.53, 16.02 ± 0.46, and 6.22 ± 0.54 μM, respectively. Moreover, these compounds are highly selective toward AChE. Compound 10i shows AChE inhibitory activity similar to a known Food and Drug Administration (FDA)approved drug, galantamine, but with even better selectivity. Interaction analysis reveals that hydrophobic and hydrogen-bonding interactions are the primary driving forces responsible for the observed high affinity of the compound with AChE.

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Synthesis and biological evaluation of novel 8- substituted sampangine derivatives as potent inhibitor of Zn2+-Aβ complex mediated toxicity, oxidative stress and inflammation

Xie

et al. 2021

Bioorganic Chemistry

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4- Substituted sampangine derivatives: Novel acetylcholinesterase and β-myloid aggregation inhibitors

Cited by 7 publications

References 37 publications

Scaffold Hopping and Structural Modification of NSC 663284: Discovery of Potent (Non)Halogenated Aminobenzoquinones

Scaffold Hopping and Structural Modification of NSC 663284: Discovery of Potent (Non)Halogenated Aminobenzoquinones

Combined Structure and Ligand-Based Design of Selective Acetylcholinesterase Inhibitors

Synthesis and biological evaluation of novel 8- substituted sampangine derivatives as potent inhibitor of Zn2+-Aβ complex mediated toxicity, oxidative stress and inflammation

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