Synthesis, Characterization, Investigation of AChE Activities and Molecular Docking Studies of New Schiff Bases Based on Substitute Salicyl Aldehyde

Year 2022, , 185 - 192, 28.02.2022

İrfan Şahin

https://doi.org/10.15671/hjbc.1020606

Cited By: 1

Abstract

In this study, two new Schiff base compounds (4 and 5) based on substituted salicyl aldehyde were synthesized. The structures of the synthesized compounds were determined by FT-IR and 1H(13C) NMR spectroscopies. The AChE inhibition activities of the compounds were investigated. According to the results obtained, the activities of compounds 4 (IC50: 1.396 ± 0.35 M) and 5 (IC50: 0.795 ± 0.47M) were found to be significantly effective than Tacrin (TAC) (IC50: 166.10 ± 17.53 M) (currently used drug). The interaction types and binding energies of compound 5, which has higher activity, were investigated by molecular docking studies.

Keywords

Schiff base, AChE inhibition activity, molecular docking

Thanks

I would like to thank to Prof. Dr. Ferhan TÜMER for valuable help and interpreting the data. I would like to thank to Dr. Özge GÜNGÖR and Seyit Ali GÜNGÖR for biological activity and molecular docking studies.

Subtitüe Salisil Aldehit Temelli Yeni Schiff Bazlarının Sentezi, Karakterizasyonu, AChE Aktivitelerinin İncelenmesi ve Moleküler Yerleştirme Çalışmaları

Abstract

Bu çalışmada, substitute salisil aldehit temelli yeni Schiff bazları (4 ve 5) sentezlendi. Sentezlenen bileşiklerin yapıları FT-IR, 1H(13C) NMR spektroskopileri ile aydınlatıldı. Bileşiklerin AChE inhibisyon aktiviteleri araştırıldı. Elde edilen sonuçlara göre 4 (IC50: 1.396 ± 0.35 M) ve 5 (IC50: 0.795 ± 0.47M) bileşiklerinin aktiviteleri standart olarak kullanılan Tacrinden (TAC) (IC50: 166.10 ± 17.53 M) çok daha yüksek inhibisyon aktivitesi sergilemiştir. Yüksek aktiviteye sahip olan bileşik 5’in moleküler docking çalışmaları ile etkileşim türleri ve bağlanma enerjileri hesaplanmıştır.

Keywords

Schiff bazı, AChE inhibisyon aktivitesi, moleküler yerleştirme

References

• C.M. Da Silva et al., Schiff bases: A short review of their antimicrobial activities, J. Adv. Res. 2 (1) (2011) 1–8.
• F.N. Ejiah et al., Substituent effect on spectral and antimicrobial activity of Schiff bases derived from aminobenzoic acids, Adv. Biol. Chem. 03 (05) (2013) 475–479.
• H.R. Afzal et al., Schiff Bases of Pioglitazone Provide Better Antidiabetic and Potent Antioxidant Effect in a Streptozotocin-Nicotinamide-Induced Diabetic Rodent Model, ACS Omega 6 (6) (2021) 4470–4479.
• P. Przybylski et al., Biological Properties of Schiff Bases and Azo Derivatives of Phenols, Curr. Org. Chem. 13 (2) (2009) 124–148.
• F.S. Tokalı et al., Synthesis, characterization, biological activity and molecular docking studies of novel schiff bases derived from thiosemicarbazide: Biochemical and computational approach, J. Mol. Struct. 1231 (2021).
• S. Onur et al., Synthesis, characterization and antibacterial effect of diarylmethylamine-based imines, J. Mol. Struct. 1214 (2020).
• S. Onur et al., New imino-methoxy derivatives: design, synthesis, characterization, antimicrobial activity, DNA interaction and molecular docking studies, J. Biomol. Struct. Dyn. 0 (0) (2021) 1–13.
• G. Bringmann et al., Full Papers, 67 (5) (2004) 5–10.
• S. Afrin Dalia et al., A short review on chemistry of schiff base metal complexes and their catalytic application, ~ 2859 ~ Int. J. Chem. Stud. 6 (3) (2018) 2859–2866.
• C. Jang et al., Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay, Sci. Rep. 8 (1) (2018) 1–21.
• E. Beal, Alzheimer disease:, Nat. Rev. Neurol. 7 (9) (2011) 474.
• Alzheimer’s Association, 2021 Alzheimer’s disease facts and figures special report Race, Ethnicity and Alzheimer’s in America, Alzheimers. Dement. 17 (3) (2021) 327–406.
• A. Rønneberg et al., The Editor recommends this issue’s article to the reader, Int. J. Paediatr. Dent. 29 (6) (2019) 683.
• S. Duong, T. Patel, and F. Chang, Dementia: What pharmacists need to know, Can. Pharm. J. 150 (2) (2017) 118–129.
• R.G. Jahn, Introduction, Role Conscious. Phys. World (2019) 1–5.
• H.R. Brunnström and E.M. Englund, Cause of death in patients with dementia disorders, Eur. J. Neurol. 16 (4) (2009) 488–492.
• J. Massoulié et al., Molecular and cellular biology of cholinesterases, Prog. Neurobiol. 41 (1) (1993) 31–91.
• M.S. More et al., Metal complexes driven from Schiff bases and semicarbazones for biomedical and allied applications: a review, Mater. Today Chem. 14 (2019) 100195.
• P. Chandra Mohan and J. Venkateshwar Rao, Biological evaluation of Schiff bases of new Isatin derivatives for Anti Alzheimer’s activity, Asian J. Pharm. Clin. Res. 7 (2) (2014) 114–117.
• J. Shi et al., Design, synthesis and biological evaluation of Schiff’s base derivatives as multifunctional agents for the treatment of Alzheimer’s disease, Med. Chem. Res. 30 (3) (2021) 624–634.
• G. Ceyhan et al., Structural characterization, luminescence and electrochemical properties of the Schiff base ligands, J. Lumin. 132 (11) (2012) 2917–2928.
• G.L. Ellman et al., A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem. Pharmacol. 7 (2) (1961) 88–95.
• O. Gungor, M. Kose, and T.T. Tok, A biguanide derivative and its cyclic anologue: Structural chracterization, AChE inhibitory effect and docking studies, J. Mol. Struct. 1196 (2019) 491–498.
• O. Gungor, S.N.K. Kurtar, and M. Kose, Water soluble biguanide salts and their 1,3,5-triazine derivatives as inhibitors of acetylcholinesterase and α-glucosidase, Zeitschrift Fur Krist. - Cryst. Mater. 235 (10) (2020) 465–475.
• U. Atmaca et al., Novel hypervalent iodine catalyzed synthesis of α-sulfonoxy ketones: Biological activity and molecular docking studies, J. Mol. Struct. 1239 (2021).
• B.J. Bennion et al., A wrench in the works of human acetylcholinesterase: Soman induced conformational changes revealed by molecular dynamics simulations, PLoS One 10 (4) (2015) 1–31.
• T. Mohamed et al., Selective inhibition of human acetylcholinesterase by xanthine derivatives: In vitro inhibition and molecular modeling investigations, Bioorganic Med. Chem. Lett. 23 (15) (2013) 4336–4341.
• Y. Pourshojaei et al., Phenoxyethyl Piperidine/Morpholine Derivatives as PAS and CAS Inhibitors of Cholinesterases: Insights for Future Drug Design, Sci. Rep. 9 (1) (2019) 1–19.
• B.L. De Sousa et al., Inhibition of acetylcholinesterase by coumarin-linked amino acids synthetized via triazole associated with molecule partition coefficient, J. Braz. Chem. Soc. 32 (3) (2021) 652–664.