Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile

Strel’nik, A. D.; Petukhov, A. S.; Zueva, Irina V.; Зобов, В. В.; Петров, К. А.; Nikolsky, E. E.; Balakin, Konstantin V.; Бачурин, С. О.; Shtyrlin, Yu. G.

doi:10.1016/j.bmcl.2016.06.070

Cited by 21 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This disease is associated with loss of cholinergic neurons in the brain and a decreased level of ACh. The major therapeutic target in Alzheimer's treatment approaches is the inhibition of brain AChE [26][27][28]. Additionally, in Alzheimer's and other neurologic diseases, the high level of dyshomeostatis of metal ions, especially iron ions, seriously affects brain function.…”

Section: Introductionmentioning

confidence: 99%

Nitrogen-Doped Arginine Carbon Dots and Its Metal Nanoparticle Composites as Antibacterial Agent

Suner

Şahiner

Ayyala

et al. 2020

View full text Add to dashboard Cite

Nitrogen (N)-doped arginine carbon dots (Arg CD) were successfully synthesized using arginine as the amine source and citric acid as the carbon source via a one-pot green synthesis microwave-assisted technique in 2 min. Ag and Cu nanoparticles (NP) were generated within N-doped Arg CDs as composite Arg-Ag CDs and Arg-Cu CDs to render enhanced antibacterial properties. TEM analysis revealed that Arg CDs are in graphitic structures with d spacing ranging from 0.5 nm to 10 nm. The minimum inhibition concentration (MIC) values of Arg CDs with 6.250 mg/mL were decreased by about 100-fold for Arg-Ag CDs and ten-fold for Arg-Cu CDs with 0.062 and 0.625 mg/mL MIC values against Staphylococcus aureus (S. aureus). The highest antibacterial susceptibility was observed for the Arg-Ag CD composite with 0.125 and 0.312 mg/mL minimum bactericidal concentration (MBC) values against Gram negative S. aureus and Gram positive Escherichia coli (E. coli) bacteria strains, respectively. It was found that the metal NPs within Arg CDs significantly increased the antibacterial properties of CDs making them available in the treatment of infections caused by different bacterial species. Furthermore, Arg-Ag CD and Arg-Cu CD composites were tested for Acetylcholinesterase (AChE, E.C. 3.1.1.7) that break down acetylcholine (ACh) into choline and acetic acid leading to the loss of ACh which plays an essential role as neurotransmitter in Alzheimer disease. It was found that Arg-Cu CDs inhibited 74.9 ± 0.8% and Arg-Ag CDs inhibited 52.1 ± 3.8% of AChE at a 1.82 mg/mL concentration versus no inhibition for Arg-CD. Moreover, the chelating activity of Arg-Cu CDs and Arg-Ag CDs were tested for Fe(II) and it was found that almost 100% chelating was attained at 116 μg composites versus no measurable chelation for bare Arg CDs, suggesting the potential neurodegenerative disease treatment properties of these composite CDs in the brain.

show abstract

Section: Introductionmentioning

confidence: 99%

Nitrogen-Doped Arginine Carbon Dots and Its Metal Nanoparticle Composites as Antibacterial Agent

Suner

Şahiner

Ayyala

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The effect of the drug starts in 15-30 min, reaches maximum in 1-2 hours, and lasts 3-4 hours or longer. Pyridostigmine bromide, used for the treatment of MG and for protection against exposure to nerve agents, is a carbamate-derived reversible AChE inhibitor [23][24][25]. Due to the quaternary amine structure, it is relatively weakly absorbed from the gastrointestinal system.…”

Section: Pyridostigminementioning

confidence: 99%

Anticholinesterases

Özdemi̇r¹,

Alagöz²

2019

Selected Topics in Myasthenia Gravis

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Although the role of AChE in cholinergic transmission is well known, the role of BChE has not been elucidated sufficiently. The hydrolysis of acetylcholine in the synaptic healthy brain cells is mainly carried out by AChE; it is accepted that the contribution to the hydrolysis of BChE is very low, but both AChE and BChE are known to play an active role in neuronal development and cholinergic transmission. Myasthenia gravis (MG) is a muscle disease characterized by weakness in skeletal muscles and rapid fatigue. Anticholinesterases, which are not only related to the immune origin of the disease but also have only symptomatic benefit, have an indispensable role in the treatment of MG. Pyridostigmine, distigmine, neostigmine, and ambenonium are the standard anticholinesterase drugs used in the symptomatic treatment of MG. All of these compounds may increase the response of the myasthenic muscle to recurrent nerve impulses, primarily by protecting the endogenous ACh.

show abstract

“…In particular, pyridoxine molecules carrying a 5-ethenyl substituent possess anti-inflammatory properties [1], 6-phenylethenyl substituted pyridoxines have been described as purine receptor antagonists [2], and 2-ethenyl derivatives possess antitumor activity [3]. In our group, we have systematically studied the chemistry and biological activity of pyridoxine derivatives (e.g., [4][5][6][7][8]). Recently, we described a number of cis-and trans-5-alkenyl substituted pyridoxines which demonstrated promising antitumor activity [7].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antitumor Activity of Novel Pyridoxine-Based Bioisosteric Analogs of trans-Stilbenes

Pugachev

Nguyen

Bulatov

et al. 2017

Journal of Chemistry

Self Cite

View full text Add to dashboard Cite

A series of trans-6-phenylethenyl substituted pyridoxine derivatives, novel bioisosteric analogs of drugs based on trans-stilbene scaffold, were synthesized using the Wittig reaction of a bis-triphenylphosphonium pyridoxine derivative with various aromatic aldehydes. Two compounds demonstrated high activity against the estrogen-dependent MCF-7 (breast cancer) cell line with IC 50 in the range of 1.9-7.9 M and very good selectivity for other studied normal and tumor cells, including the estrogen receptor negative MDA-MB-231 breast cancer cells. The active compounds possessed an intense blue fluorescence, and this feature allowed us to effectively visualize them in cytoplasm and in nucleus. The obtained results make the described chemotype a promising starting point for the development of new anticancer agents for the therapy of estrogen-dependent malignancies.

show abstract

Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile

Cited by 21 publications

References 18 publications

Nitrogen-Doped Arginine Carbon Dots and Its Metal Nanoparticle Composites as Antibacterial Agent

Nitrogen-Doped Arginine Carbon Dots and Its Metal Nanoparticle Composites as Antibacterial Agent

Anticholinesterases

Synthesis and Antitumor Activity of Novel Pyridoxine-Based Bioisosteric Analogs of trans-Stilbenes

Contact Info

Product

Resources

About