Design, synthesis and biological assessment of acridine derivatives containing 1,3,4-thiadiazole moiety as novel selective acetylcholinesterase inhibitors

Lotfi, Safa; Rahmani, Talat; Hatami, Maryam; Pouramiri, Behjat; Kermani, Esmat Tavakolinejad; Rezvannejad, Elham; Mortazavi, Mojtaba; Fathi Hafshejani, Shahnaz; Askari, Nahid; Pourjamali, Nader; Zahedifar, Mahboobeh

doi:10.1016/j.bioorg.2020.104457

Cited by 19 publications

(8 citation statements)

References 46 publications

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“…The anticholinesterases are also used to manage other forms of neurological disorders, such as ataxia, PD, dementia with Lewy bodies, senile dementia, vascular dementia, Down's syndrome, Korsakoff disease, and myasthenia gravis (Farmakidis et al, 2018; Kulshreshtha & Piplani, 2016; Mukherjee et al, 2007). Nowadays, there are worldwide research efforts for the design and development of novel cholinesterase inhibitors with more efficacy and fewer side effects (Lotfi et al, 2020; Mariki et al, 2021; Sharma, 2019). The identification of new potent anticholinesterase compounds through the study of natural resources has also attracted a lot of attention (Dey et al, 2017; Dos Santos et al, 2018; Houghton et al, 2006; Mukherjee et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Correlation between total phenolic and flavonoid contents and biological activities of 12 ethanolic extracts of Iranian propolis

Fathi Hafshejani

Lotfi

Rezvannejad

et al. 2023

Food Science & Nutrition

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Propolis is a resinous substance produced by honey bees that is very popular as a natural remedy in traditional medicine. The current research is the first study on the biological properties of ethanolic extracts of propolis (EEP) from several different regions (12) of Iran. Total phenolic and flavonoid contents (TPC and TFC) of Iranian EEPs were variable between 26.59-221.38 mg GAE/g EEP and 4.8-100.03 mg QE/g EEP. The DPPH scavenging assay showed all the studied EEP samples, except for the sample with the lowest TPC and TFC (P6), have suitable antioxidant activity. All the EEPs inhibited both cholinesterase enzymes (acetylcholinesterase: AChE, butyrylcholinesterase: BuChE) but most of them exhibited a distinct selectivity over BuChE.Evaluation of the antibacterial activity of the EEP samples using four pathogenic bacteria (B. cereus, S. aureus, A. baumannii, and P. aeruginosa) demonstrated that the antibacterial properties of propolis are more effective on the gram-positive bacterium.Spearman correlation analysis showed a strong positive correlation between TPC and TFC of the Iranian EEPs and their antioxidant, anticholinesterase, and antibacterial activities. Considering that there is ample evidence of anticholinesterase activity of flavonoids and a significant correlation between the anticholinesterase activity of the studied Iranian EEPs and their total flavonoid content was observed, the interaction of 17 well-known propolis flavonoids with AChE and BuChE was explored using molecular docking. The results indicated that all the flavonoids interact with the active site gorge of both enzymes with high affinity. Summing up, the obtained results suggest that Iranian propolis possesses great potential for further studies.

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Section: Resultsmentioning

confidence: 99%

Correlation between total phenolic and flavonoid contents and biological activities of 12 ethanolic extracts of Iranian propolis

Fathi Hafshejani

Lotfi

Rezvannejad

et al. 2023

Food Science & Nutrition

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“…Anticholinesterase (AChE) activity evaluation of the derivatives showed that all the derivatives are capable of inhibiting both enzymes and are highly selective towards AChE. Among them, the ability of 163 and 164 with respective IC 50 values of 0.002 and 0.006 µM to inhibit AChE was higher than tacrine (IC 50 = 0.016 µM) 235 ( Table 6 ).…”

Section: Synthetic Cholinesterase Inhibitorsmentioning

confidence: 99%

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

et al. 2022

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“…Since these heterocyclic rings are compounds with a broad spectrum of biological activity they are important pharmacophores in medicinal chemistry [28–35] . Additionally, 1,2,4‐triazole and 1,3,4‐thiadiazole derivates are active compounds as cholinesterase inhibitors for the treatment of AD [36–40] …”

Section: Introductionmentioning

confidence: 99%

“…[28][29][30][31][32][33][34][35] Additionally, 1,2,4-triazole and 1,3,4-thiadiazole derivates are active compounds as cholinesterase inhibitors for the treatment of AD. [36][37][38][39][40] Molecular hybridization is a concept based on combining different bioactive pharmacophores to design and obtain new compounds with less side effects and higher biological activity. [41] In this study, new hybrid molecules benzoxazoloneÀ thiosemicarbazide, benzoxazoloneÀ 1,2,4triazole and benzoxazoloneÀ 1,3,4-thiadiazole were designed and synthesized by combining the active pharmacophores thiosemicarbazide, 1,2,4-triazole and 1,3,4-thiadiazole with benzoxazolone (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Benzoxazolone−Thiosemicarbazide, 1,2,4‐Triazole, 1,3,4‐Thiadiazole Derivatives as Cholinesterase Inhibitors

Koçak Aslan,

Sağlık,

Özkay

et al. 2023

ChemistrySelect

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In this study, a new series of benzoxazolone−thiosemicarbazide/1,2,4‐triazole/1,3,4‐thiadiazole hybrids were designed and synthesized. The structures of novel compounds were elucidated by spectral methods (IR, 1H‐NMR, 13C‐NMR, ESI‐MS) and elemental analyses. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activity of the compounds were investigated using in vitro Ellman method using donepezil and tacrin as the standards. Although none of compounds showed significant inhibitor activity on BuChE, compounds 2 c, 3 a, 4 a and 5 b displayed good inhibitory activities on AChE with IC50 values of 0.031, 0.049, 0.117 and 0.085 μg/mL, respectively. Molecular docking studies were carried out performed to the interactions with the active site of the enzyme (PDB:4EY7) and enzyme kinetics studies were performed for the most potent AChE inhibitor compound 2 c.

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Design, synthesis and biological assessment of acridine derivatives containing 1,3,4-thiadiazole moiety as novel selective acetylcholinesterase inhibitors

Cited by 19 publications

References 46 publications

Correlation between total phenolic and flavonoid contents and biological activities of 12 ethanolic extracts of Iranian propolis

Correlation between total phenolic and flavonoid contents and biological activities of 12 ethanolic extracts of Iranian propolis

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

Synthesis and Biological Evaluation of Benzoxazolone−Thiosemicarbazide, 1,2,4‐Triazole, 1,3,4‐Thiadiazole Derivatives as Cholinesterase Inhibitors

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