Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives

Ishaq, Muhammad; Taslimi, Parham; Shafiq, Zahid; Khan, Samra; Salmas, Ramin Ekhteiari; Zangeneh, Mohammad Mahdi; Saeed, Aamer; Zangeneh, Akram; Sadeghian, Nastaran; Asari, Asnuzilawati; Mohamad, Habsah

doi:10.1016/j.bioorg.2020.103924

Cited by 41 publications

(18 citation statements)

References 48 publications

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“…The 1 H‐NMR spectra of compounds 1 – 8 were displayed in Figure S2 . The singlet peaks at 11.95–11.28 and 10.24–9.56 ppm were assigned to CN−H and NN−H groups, respectively, which was similar to those reported in relative literature [30,31] . The azomethine proton, HC=N, situated at 8.22–7.71 ppm as a singlet peak and was close to the reported value [31] .…”

Section: Resultssupporting

confidence: 88%

Synthesis, Crystal Structure, Biological Evaluation and in Silico Studies on Novel (E)‐1‐(Substituted Benzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone Derivatives

Fan

Qi²,

Song

et al. 2021

Chemistry & Biodiversity

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A series of (E)‐1‐(substituted benzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone derivatives were synthesized and characterized by FT‐IR spectrum, elemental analysis, NMR spectrum, HR‐MS spectrum, and X‐ray single crystal diffraction technology. The crystal structures and packing of (E)‐1‐(4‐fluorobenzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone and (E)‐1‐(3‐fluorobenzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone were maintained through the intramolecular hydrogen bond (N3‐H6⋅⋅⋅N1) and intermolecular hydrogen bonds (N2‐H4⋅⋅⋅S1, C14‐H14⋅⋅⋅F1 and C7‐H7⋅⋅⋅S1). The results obtained by employing the DPPH free radicals scavenging assay indicated that (E)‐1‐(4‐methoxylbenzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone had a more significant antioxidant activity compared with other compounds. The results measured by adopting the disc diffusion method elucidated that (E)‐1‐(4‐trifluoromethylbenzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone possessed a more prominent antifungal activity than other compounds. Molecular docking showed that (E)‐1‐(4‐chlorobenzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone had the highest affinity with receptor protein (1NMT). Moreover, the drug‐likeness characteristic, physicochemical properties, pharmacokinetic profiles, and bioactivity scores of all the compounds were predicted through in silico studies. The results illustrated that (E)‐1‐(4‐fluorobenzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone had the drug‐likeness characteristic and all the compounds were considered as moderately biological active molecules.

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Section: Resultssupporting

confidence: 88%

Synthesis, Crystal Structure, Biological Evaluation and in Silico Studies on Novel (E)‐1‐(Substituted Benzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone Derivatives

Fan

Qi²,

Song

et al. 2021

Chemistry & Biodiversity

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“…In parallel, thiosemicarbazones also display a wide plethora of biological properties ranging from anticancer, anti-bacterial, anti-tumor, anti-protozoal, anti-fungal, anti-leishmanial, and antiviral activities [29][30][31][32][33][34]. Thiosemicarbazone derivatives have also been employed as NDRG1 up-regulators, cathepsin inhibitors, and cholinesterase inhibitors for the treatment of Alzheimer's disease [35][36][37][38]. Figure 1 represents illustrative examples of commercial drugs for AD therapy and importance of quinoline as well as thiosemicarbazone in medicinal/pharmaceutical chemistry.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

et al. 2021

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease.

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“…[ 66 ] In this assay, AChE from electric eel ( Electrophorus electricus ) and BChE from equine serum were used. [ 67–69 ] α‐Glucosidase, which is obtained from Saccharomyces cerevisiae , inhibitory activity of new complexes ( 1a–e and 2a–e ) was determined according to the method of Tao. [ 70 ]…”

Section: Methodsmentioning

confidence: 99%

Silver N‐heterocyclic carbene complexes bearing fluorinated benzyl group: Synthesis, characterization, crystal structure, computational studies, and inhibitory properties against some metabolic enzymes

Bal

Demirci

Şen

et al. 2021

Applied Organom Chemis

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A series of the silver N‐heterocyclic carbene (NHC) complexes have been synthesized from the reactions between benzimidazolium salts bearing fluorinated benzyl group and Ag2O via the deprotonation method. All Ag(I)NHC complexes were characterized by known spectroscopic techniques (1H nuclear magnetic resonance [NMR], 13C NMR, and Fourier transform infrared [FT‐IR]) and elemental analysis. The molecular structures of the two complexes were unambiguously elucidated through single‐crystal X‐ray diffraction analysis. Namely, X‐ray studies show that the coordination geometry around the Ag(I) atom in the case of complex 2c is revealed to be almost linear with C–Ag–Cl angle, whereas in complex 2e, it appears as a nonlinear structure. The inhibitory profiles of these new complexes are investigated on some metabolic enzymes. Representatively, the most potent complex against human carbonic anhydrase isoenzymes I and II (hCAs I and II), 2d, was 1.8 times more potent than standard inhibitor acetazolamide against hCAs I and II. On the other hand, complexes 2c and 2b as most potent compounds against both cholinesterase enzymes was around 5 and 1.6 times more potent than tacrine against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively. The most active α‐glucosidase inhibitor 2d had similar activity to acarbose as a standard inhibitor. Furthermore, it confirms its in vitro studies as a result of molecular docking studies for each enzyme with (i) binding energy and inhibition constant values and (ii) the definition of the best conformation and nonbonding interactions of the related complexes (2b, 2c, and 2d) against the different target proteins.

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Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives

Cited by 41 publications

References 48 publications

Synthesis, Crystal Structure, Biological Evaluation and in Silico Studies on Novel (E)‐1‐(Substituted Benzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone Derivatives

Synthesis, Crystal Structure, Biological Evaluation and in Silico Studies on Novel (E)‐1‐(Substituted Benzylidene)‐4‐(3‐isopropylphenyl)thiosemicarbazone Derivatives

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

Silver N‐heterocyclic carbene complexes bearing fluorinated benzyl group: Synthesis, characterization, crystal structure, computational studies, and inhibitory properties against some metabolic enzymes

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