Synthesis, structural elucidation and bioevaluation of 4-amino-1,2,4-triazole-3-thione’s Schiff base derivatives

Rafiq, Muhammad; Saleem, Muhammad; Hanif, Muhammad; Kang, Sung Kwon; Seo, Sung‐Yum; Lee, Ki Hwan

doi:10.1007/s12272-015-0688-2

Cited by 20 publications

(2 citation statements)

References 37 publications

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“…A series of experiments were performed to determine the inhibition kinetics by following method 41 , 42 . Inhibitor 5c with concentrations 0.0, 0.0005, 0.0022, 0.0045, 0.009, 0.018 µM and 5d with concentrations 0.0, 1.75, 3.5, 7, 14 and 28 µM, respectively, were used.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, computational studies, tyrosinase inhibitory kinetics and antimelanogenic activity of hydroxy substituted 2-[(4-acetylphenyl)amino]-2-oxoethyl derivatives

Rafiq

Nazir

Ashraf

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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The over expression of melanogenic enzymes like tyrosinase caused many hyperpigmentaion disorders. The present work describes the synthesis of hydroxy substituted 2-[(4-acetylphenyl)amino]-2-oxoethyl derivatives 3a-e and 5a-e as antimelanogenic agents. The tyrosinase inhibitory activity of synthesized derivatives 3a-e and 5a-e was determined and it was found that derivative 5c possesses excellent activity with IC 50 ¼ 0.0089 mM compared to standard kojic acid (IC 50 ¼ 16.69 mM). The presence of hydroxyl groups at the ortho and the para position of cinnamic acid phenyl ring in compound 5c plays a vital role in tyrosinase inhibitory activity. The compound 5d also exhibited good activity (IC 50 ¼ 8.26 mM) compared to standard kojic acid. The enzyme inhibitory kinetics results showed that compound 5c is a competitive inhibitor while 5d is a mixed-type inhibitor. The mode of binding for compounds 5c and 5d with tyrosinase enzyme was also assessed and it was found that both derivatives irreversibly bind with target enzyme. The molecular docking and molecular dynamic simulation studies were also performed to find the position of attachment of synthesized compounds at tyrosinase enzyme (PDB ID 2Y9X). The results showed that all of the synthesized compounds bind well with the active binding sites and most potent derivative 5c formed stable complex with target protein. The cytotoxicity results showed that compound 5c is safe at a dose of 12 mg/mL against murine melanoma (B16F10) cells. The same dose of 5c was selected to determine antimelanogenic activity; the results showed that it produced antimelenogenic effects in murine melanoma (B16F10) cells. Based on our investigations, it was proposed that compound 5c may serve as a lead structure to design more potent antimelanogenic agents.

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Section: Methodsmentioning

confidence: 99%

Synthesis, computational studies, tyrosinase inhibitory kinetics and antimelanogenic activity of hydroxy substituted 2-[(4-acetylphenyl)amino]-2-oxoethyl derivatives

Rafiq

Nazir

Ashraf

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Based upon the antityrosinase assay, the most potent derivative (5c) was chosen for kinetic inhibition studies using enzyme and L-DOPA as a substrate [35][36][37]. Various concentrations of the inhibitor 5c were among 0.00 to 0.013 μM and that of L-DOPA was 0.00 to 0.0064 μM during all kinetic assays.…”

Section: Mushroom Tyrosinase Inhibitory Kineticsmentioning

confidence: 99%

Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis

Nazir

Rafique

Roshan

et al. 2022

BioMed Research International

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Tyrosinase and its related proteins are responsible for pigmentation disorders, and inhibiting tyrosinase is an established strategy to treat hyperpigmentation. The carbonyl scaffolds can be effective inhibitors of tyrosinase activity, and the fact that both benzoic and cinnamic acids are safe natural substances with such a scaffolded structure, it was speculated that hydroxyl-substituted benzoic and cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. These moieties were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase with a view to explore antimelanogenic ingredients. The most active compound, 2-((3-acetylphenyl)amino)-2-oxoethyl(E)-3-(2,4-dihydroxyphenyl)acrylate (5c), inhibited mushroom tyrosinase with an IC50 of 0.0020 ± 0.0002 μ M , while 2-((3-acetylphenyl)amino)-2-oxoethyl 2,4-dihydroxybenzoate (3c) had an IC50 of 27.35 ± 3.6 μ M in comparison to the positive control arbutin and kojic acid with a tyrosinase inhibitory activity of IC50 of 191.17 ± 5.5 μ M and IC50 of 16.69 ± 2.8 μ M , respectively. Analysis of enzyme kinetics revealed that 5c is a competitive and reversible inhibitor with dissociation constant (Ki) value 0.0072 μM. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the enzymatic pocket for these compounds. The orthohydroxyl of the cinnamic acid moiety of 5c is predicted to form hydrogen bond with the active site side chain carbonyl of Asn 260 (2.16 Å) closer to the catalytic site Cu ions. The acetyl carbonyl is picking up another hydrogen bond with Asn 81 (1.90 Å). The inhibitor 5c passed the panassay interference (PAINS) alerts. This study presents the potential of hydroxyl-substituted benzoic and cinnamic acids and could be beneficial for various cosmetic formulations.

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Investigation of the Properties of 1,2,4‐Triazole‐3‐thione Schiff Base Derivatives by Urease Inhibition as Therapeutic or Agrochemical Candidate Molecules

Zehir Kirkbir,

Gultekin,

Kolcuoglu

et al. 2024

ChemistrySelect

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With the production of bacterial urease, bacteria can provide the best conditions for colonization and survival of the stomach in acidic environment. Due to this reproductive ability, H. pylori can cause various diseases such as cancer, urinary tract infections, and peptic ulcer in human metabolism. Consequently, the discovery of substances that can inhibit urease activity holds great promise for treating certain diseases. In this study, Schiff base derivatives of 1,2,4‐triazole‐3‐thione were synthesized in good to excellent yields. The structures of the obtained compounds were elucidated using spectroscopic techniques, such as FT‐IR, 1H‐NMR and 13C‐NMR. The urease inhibitory activities of the obtained products were evaluated against the reference inhibitor thiourea. Out of these compounds, compound 6 c exhibited the highest inhibitory effectiveness, with an IC50 value of 0.0109 μM against refenrence inhibitor (IC50=11 μM). Kinetic studies revealed that compound 6 c acts as a non‐competitive inhibitor. According to the results of the docking studies, compound 6 c exhibited the highest binding affinity (with the lowest ΔG value as −8.4 kcal/mol) and efficiently interacted with the enzyme as a potent inhibitor among all the molecules examined in the study.

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Synthesis, structural elucidation and bioevaluation of 4-amino-1,2,4-triazole-3-thione’s Schiff base derivatives

Cited by 20 publications

References 37 publications

Synthesis, computational studies, tyrosinase inhibitory kinetics and antimelanogenic activity of hydroxy substituted 2-[(4-acetylphenyl)amino]-2-oxoethyl derivatives

Synthesis, computational studies, tyrosinase inhibitory kinetics and antimelanogenic activity of hydroxy substituted 2-[(4-acetylphenyl)amino]-2-oxoethyl derivatives

Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis

Investigation of the Properties of 1,2,4‐Triazole‐3‐thione Schiff Base Derivatives by Urease Inhibition as Therapeutic or Agrochemical Candidate Molecules

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