From Isoniazid to 2-Pyrazolines: Synthesis, In silico Behaviour and Antimicrobial Activity DOI Open Access
Geetha Birudala, Gurinderdeep Singh,

S. Abdur Rahman Junaid Nayeem

et al.

Asian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 36(8), P. 1812 - 1820

Published: July 25, 2024

This study explores the synthesis, in silico behaviour and antimicrobial activity of isoniazid derived 2-pyrazolines as potential drugs for tuberculosis bacterial infections. The investigation encompasses computational studies molecular efficacy assessment. Incorporating established like is explored to enhance their pharmacological properties. synthesized compounds were characterized by analytical techniques such IR, NMR, mass spectral analysis elemental analysis. Synthesized pyrazolines 4a-j evaluated vitro antitubercular antibacterial activities against various biological strains. In provides valuable insights into ADMET descriptors, confirming good pharmacokinetic suggests these templates developing new anti-mycobacterial agents, guiding design novel with improved therapeutic potential.

Language: Английский

Cinnamic acid conjugated with triazole acetamides as anti-Alzheimer and anti-melanogenesis candidates: an in vitro and in silico study DOI Creative Commons

Amir Shervin Shokouhi Asl,

Mohammad Hosein Sayahi, Mohammad Hashem Hashempur

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 3, 2025

In this study, new cinnamic acid linked to triazole acetamide derivatives was synthesized and evaluated for anti-Alzheimer anti-melanogenesis activities. The structural elucidation of all analogs performed using different analytical techniques, including 1H-NMR, 13C-NMR, mass spectrometry, IR spectroscopy. compounds were assessed in vitro their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase enzymes. Among synthesize derivative compound 3-(4-((1-(2-((2,4-dichlorophenyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxyphenyl)acrylic (10j) exhibited the highest activity BChE with an IC50 value 11.99 ± 0.53 µM. Derivative 3-(3-methoxy-4-((1-(2-oxo-2-(p-tolylamino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)acrylic (10d), bearing a 4-CH3 group, identified as most potent AChE inhibitor. terms inhibition, 3-(3-methoxy-4-((1-(2-((2-methyl-4-nitrophenyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)acrylic (compound 10n), demonstrated 44.87% inhibition at concentration 40 Additionally, kinetic study 10j which 2,4-dichlorophenyl substituents revealed mixed-type pattern. Furthermore, molecular docking dynamic studies conducted thoroughly evaluate its mode action within active site.

Language: Английский

Citations

1
Anticholinesterase activities of novel isoindolin-1,3-dione-based acetohydrazide derivatives: design, synthesis, biological evaluation, molecular dynamic study DOI Creative Commons

Ahmad Nazarian,

Fahimeh Abedinifar, Haleh Hamedifar

et al.

BMC Chemistry, Journal Year: 2024, Volume and Issue: 18(1)

Published: April 1, 2024

Abstract In pursuit of developing novel cholinesterase (ChE) inhibitors through molecular hybridization theory, a series isoindolin-1,3-dione-based acetohydrazides (compounds 8a – h ) was designed, synthesized, and evaluated as possible acetylcholinesterase (AChE) butyrylcholinesterase (BChE) inhibitors. vitro results revealed IC 50 values ranging from 0.11 ± 0.05 to 0.86 0.02 µM against AChE 5.7 0.2 30.2 2.8 BChE. A kinetic study conducted on the most potent compound, , ascertain its mode inhibition, revealing competitive AChE. Furthermore, binding interaction modes active compound within site elucidated. Molecular dynamics simulations were performed assess stability -AChE complex. silico pharmacokinetic predictions for compounds indicated their potential promising lead structure development new anti-Alzheimer’s disease (anti-AD) agents.

Language: Английский

Citations

4
Role of Pyrazole Moiety in the Treatment of Alzheimer's Disease: A Comprehensive Review of Various Synthetic Routes and Probable Mechanisms of Action DOI
Aman Thakur, Ranjit Singh, Vineet Mehta

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(13)

Published: March 31, 2025

Abstract Alzheimer's disease (AD) has emerged as a healthcare burden in recent times both, developing and developed nations. This could be attributed to the involvement of complex pathology limited treatment options available for management AD. Currently, therapeutic strategies fail cure or reverse AD associated complications are primarily focused on providing symptomatic relief. Therefore, need identify novel strategy become evident, which pyrazole‐based moieties being considered promising options. Pyrazole one most widely exploited heterocyclic against various disorders holds great potential development anti‐Alzheimer drugs. The current review focuses advances synthetic approaches employed pyrazole analogs their mechanisms action. structural activity relationship these derivatives certain targets also been discussed may help draw new ideas potent anti‐AD derivatives.

Language: Английский

Citations

0
Design and synthesis of new 1,2,3-triazole-methoxyphenyl-1,3,4-oxadiazole derivatives: selective butyrylcholinesterase inhibitors against Alzheimer’s disease DOI Creative Commons
Aida Iraji, Roshanak Hariri, Mohammad Hashem Hashempur

et al.

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: April 15, 2025

Alzheimer's disease (AD) remains a significant public health challenge due to its progressive cognitive impairment and the absence of proven treatments. In this study, several novel 1,2,3-triazole-methoxyphenyl-1,3,4-oxadiazole derivatives were synthesized evaluated for their ability inhibit key enzymes associated with AD: acetylcholinesterase (AChE) butyrylcholinesterase (BChE). Structure-activity relationship (SAR) analysis revealed that featuring electron-withdrawing groups, particularly nitro fluorine substituents, exhibited remarkable inhibitory activity against BChE while showing minimal effectiveness AChE. Among these, compound 13s (R = 4-CH3, R' 4-NO2) demonstrated highest potency, selectively targeting an IC50 value 11.01 µM. Molecular docking molecular dynamics (MD) simulations provided deeper insights into favorable interactions between these compounds BChE. Additionally, cytotoxicity studies confirmed active compound's limited toxicity toward normal cells, indicating promising therapeutic profile. These findings suggest selective anti-BChE hold potential consideration in later stages AD treatment.

Language: Английский

Citations

0
Current pharmacophore based approaches for the development of new anti-Alzheimer’s agents DOI
Prachi Sharma,

Sunil Sharma,

Yogesh Yadav

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 113, P. 117926 - 117926

Published: Sept. 13, 2024

Language: Английский

Citations

3
Synthesis of novel aryl-substituted 2-aminopyridine derivatives by the cascade reaction of 1,1-enediamines with vinamidinium salts to develop novel anti-Alzheimer agents DOI Creative Commons

Sama Loori,

Hormoz Pourtaher,

Abdolmohammad Mehranpour

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 14, 2024

Abstract Alzheimer’s disease (AD), a severe neurodegenerative disorder, imposes socioeconomic burdens and necessitates innovative therapeutic strategies. Current interventions are limited underscore the need for novel inhibitors of acetylcholinesterase (AChE) butyrylcholinesterase (BChE), enzymes implicated in pathogenesis AD. In this study, we report synthetic strategy generation 2-aminopyridine derivatives via two-component reaction converging aryl vinamidinium salts with 1,1-enediamines (EDAMs) dimethyl sulfoxide (DMSO) solvent system, catalyzed by triethylamine (Et 3 N). The protocol introduces rapid, efficient, scalable pathway, achieving good to excellent yields while maintaining simplistic workup procedures. Seventeen were synthesized subsequently screened their inhibitory activity against AChE BChE. most potent derivative, 3m , exhibited an IC 50 value 34.81 ± 3.71 µM 20.66 1.01 BChE compared positive control donepezil 0.079 0.05 10.6 2.1 Also, detailed kinetic studies undertaken elucidate modes enzymatic inhibition compounds both promising compound was then subjected molecular docking dynamics simulations, revealing significant binding affinities favorable interaction profiles silico ADMET assessments further determined drug-like properties suggesting it as candidate pre-clinical development.

Language: Английский

Citations

2
5-methyl-N'-(thiophen-2-ylmethylene)-1H-pyrazole-3-carbohydrazide as potent anticancer agent: Synthesis, spectroscopic characterization, anticancer activity and DFT studies DOI
Issam Ameziane El Hassani, Silvia Antonia Brandán, Ahmet Altay

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: unknown, P. 140919 - 140919

Published: Nov. 1, 2024

Language: Английский

Citations

2
From Isoniazid to 2-Pyrazolines: Synthesis, In silico Behaviour and Antimicrobial Activity DOI Open Access
Geetha Birudala, Gurinderdeep Singh,

S. Abdur Rahman Junaid Nayeem

et al.

Asian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 36(8), P. 1812 - 1820

Published: July 25, 2024

This study explores the synthesis, in silico behaviour and antimicrobial activity of isoniazid derived 2-pyrazolines as potential drugs for tuberculosis bacterial infections. The investigation encompasses computational studies molecular efficacy assessment. Incorporating established like is explored to enhance their pharmacological properties. synthesized compounds were characterized by analytical techniques such IR, NMR, mass spectral analysis elemental analysis. Synthesized pyrazolines 4a-j evaluated vitro antitubercular antibacterial activities against various biological strains. In provides valuable insights into ADMET descriptors, confirming good pharmacokinetic suggests these templates developing new anti-mycobacterial agents, guiding design novel with improved therapeutic potential.

Language: Английский

Citations

0