Densely substituted piperidines as a new class of elastase inhibitors: Synthesis and molecular modeling studies

Hamdani, Syeda Shamila; Khan, Bilal Ahmad; Saeed, Aamer; Larik, Fayaz Ali; Channar, Pervaiz Ali; Ahmad, Kamsuriah; Mughal, Ehsan Ullah; Abbas, Qamar; Amin, Noha H.; Ali, M. A.; Maitlo, Habibullah; Hassan, Mubashir; Raza, Hussain

doi:10.1002/ardp.201900061

Cited by 12 publications

(7 citation statements)

References 39 publications

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“…The one-step five-component synthetic route was implemented to access the desired piperidine FTEAA as shown in Scheme . The reported procedure was followed to prepare the desired compound. , The purity was established based on thin-layer chromatography. The structure of FTEAA was confirmed on the basis of 1 H and 13 C NMR, FT-IR, and single-crystal XRD analysis.…”

Section: Methodsmentioning

confidence: 99%

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Exploring Highly Functionalized Tetrahydropyridine as a Dual Inhibitor of Monoamine Oxidase A and B: Synthesis, Structural Analysis, Single Crystal XRD, Supramolecular Assembly Exploration by Hirshfeld Surface Analysis, and Computational Studies

et al. 2022

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Ethyl 4-(4-fluorophenylamino)-2,6-bis(4-(trifluoromethyl)phenyl)-1-(4-fluoro-phenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate ( FTEAA ) has been synthesized efficiently in an iodine-catalyzed five-component reaction of 4-fluoroaniline, 4-trifluoromethyl benzaldehyde, and ethyl acetoacetate in methanol at 55 °C for 12 h. Various spectro-analytical techniques such as 1 H and 13 C NMR and Fourier-transform infrared spectroscopy have validated the structure of FTEAA . Further confirmation of the structure of FTEAA has been established on the basis of single-crystal X-ray diffraction analysis. The supramolecular assembly of FTEAA in terms of strong and comparatively weak noncovalent interactions is fully investigated by Hirshfeld surface analysis, the interaction energy between pairs of molecules, and energy frameworks. The void analysis is conducted to explore the strength and stability of the crystal structure. Furthermore, molecular docking analysis was computationally performed to see the potential intermolecular interactions between the selected proteins and FTEAA . The binding interaction energies are found to be −8.8 and −9.6 kcal/mol for the proteins MAO-B (PDB ID: 2V5Z ) and MAO-A (PDB ID: 2Z5X ), respectively. These reasonably good binding energies (more negative values) indicate the efficient associations between the FTEAA and target proteins. The proteins and FTEAA were also analyzed for intermolecular interactions. FTEAA and proteins interact in a variety of ways, like conventional hydrogen bonds, carbon–hydrogen bonds, alkyl, π-alkyl, and halide interactions.

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Section: Methodsmentioning

confidence: 99%

“…The reported procedure was followed to prepare the desired compound. 45,46 The purity was established based on thin-layer chromatography. The structure of FTEAA was confirmed on the basis of 1 H and 13 C NMR, FT-IR, and singlecrystal XRD analysis.…”

Section: Materials and Techniquesmentioning

confidence: 99%

Exploring Highly Functionalized Tetrahydropyridine as a Dual Inhibitor of Monoamine Oxidase A and B: Synthesis, Structural Analysis, Single Crystal XRD, Supramolecular Assembly Exploration by Hirshfeld Surface Analysis, and Computational Studies

et al. 2022

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“…The structures of the six compounds isolated from the leaf of C. sexangularis are presented in Figure 1. Stigmasterol (1), 17-(1-methyl-allyl)-hexadecahydro-cyclopenta[a]phenanthrene (2), β-sitosterol (3), dodecanoic acid (4), ethyl nonadecanoate (5) and ethyl stearate (6) are reported in this plant for the first time.…”

Section: Spectral Datamentioning

confidence: 96%

“…The dermal layer is structurally a flexible and reliable component of the skin [6]. Elastin within the dermal layer is one of the structural components that makes a massive contribution in tissues and tendons connection in humans because of the insolubility of elastic fibrous protein [7].…”

Section: Introductionmentioning

confidence: 99%

Steroids and Fatty Acid Esters from Cyperus sexangularis Leaf and Their Antioxidant, Anti-Inflammatory and Anti-Elastase Properties

et al. 2023

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Cyperus sexangularis (CS) is a plant in the sedges family (Cyperaceae) that grows abundantly in swampy areas. The leaf sheath of plants in the Cyperus genus are mostly used domestically for mat making, while they are implicated for skin treatment in traditional medicine. The plant was investigated for its phytochemical contents as well as its antioxidant, anti-inflammatory and anti-elastase properties. The n-hexane and dichloromethane leaf extracts were chromatographed on a silica gel column to afford compounds 1–6. The compounds were characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. The inhibitory effect of each compound against 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion radicals were determined by standard in vitro antioxidant methods. The in vitro anti-inflammatory response was measured using egg albumin denaturation (EAD) assay, while the anti-elastase activity of each compound in human keratinocyte (HaCaT) cells was also monitored. The compounds were characterized as three steroidal derivatives, stigmasterol (1), 17-(1-methyl-allyl)-hexadecahydro-cyclopenta[a]phenanthrene (2) and β-sitosterol (3), dodecanoic acid (4) and two fatty acid esters, ethyl nonadecanoate (5) and ethyl stearate (6). Stigmasterol (1) exhibited the best biological properties, with IC50 of 38.18 ± 2.30 µg/mL against DPPH, 68.56 ± 4.03 µg/mL against NO and 303.58 ± 10.33 µAAE/mg against Fe3+. At 6.25 µg/mL, stigmasterol inhibited EAD by 50%. This activity was lower when compared to diclofenac (standard), which demonstrated 75% inhibition of the protein at the same concentration. Compounds 1, 3, 4 and 5 showed comparable anti-elastase activity with an IC50 ≥ 50 µg/mL, whereas the activity of ursolic acid (standard) was double fold with an IC50 of 24.80 ± 2.60 µg/mL when compared to each of the compounds. In conclusion, this study has identified three steroids (1–3), one fatty acid (4), and two fatty acid esters (5 and 6) in C. sexangularis leaf for the first time. The compounds showed considerable antioxidant, anti-inflammatory and anti-elastase properties. Thus, the findings may serve as a justification for the folkloric use of the plant as a local skin ingredient. It may also serve to validate the biological role of steroids and fatty acid compounds in cosmeceutical formulations.

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“…Over and above natural products, several synthetic molecules have also been used for both purposes. We have already identified densely substituted piperidines and 1,4-dihydropyridines as innovative skin shielding and anti-aging agents [10,11]. Alternatively, quinolylbased acyl thioureas, and valeroyl-3-arylthioureas have been confirmed as efficient free-radical scavengers [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis, molecular docking, and enzyme inhibitory kinetics

Ujan

Channar

Saeed

et al. 2021

Journal of Heterocyclic Chem

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The porcine pancreatic elastase inhibition and free-radical scavenging play a crucial role in age progression. All the series of 10 newly synthesized benzimidazole thioureas (4a-j) were assessed for elastase inhibition and radical scavenging activity to identify the suitable anti-aging ingredient for cosmetics products. The compounds 4e, 4f, 4g, and 4h showed inhibition better than the standard, while compound 4f showed the most significant elastase inhibition with the IC 50 value of 1.318 ± 0.025 μM compared with oleanic acid IC 50 13.451 ± 0.014 used ±1.989 and 41.563 ± 0.824, respectively, as standard. Molecular docking studies were performed and the compound 4f showed binding energy of 7.2 kcal/mol. Kinetics studies revealed inhibition of the pancreatic elastase in a competitive manner. The relative binding energy and structure activity relationship (SAR) identified compound 4f as an effective inhibitor of porcine pancreatic elastase. Compounds 4e and 4i showed remarkable free-radical scavenging activity with SC 50 values of 26.421.

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Densely substituted piperidines as a new class of elastase inhibitors: Synthesis and molecular modeling studies

Cited by 12 publications

References 39 publications

Exploring Highly Functionalized Tetrahydropyridine as a Dual Inhibitor of Monoamine Oxidase A and B: Synthesis, Structural Analysis, Single Crystal XRD, Supramolecular Assembly Exploration by Hirshfeld Surface Analysis, and Computational Studies

Exploring Highly Functionalized Tetrahydropyridine as a Dual Inhibitor of Monoamine Oxidase A and B: Synthesis, Structural Analysis, Single Crystal XRD, Supramolecular Assembly Exploration by Hirshfeld Surface Analysis, and Computational Studies

Steroids and Fatty Acid Esters from Cyperus sexangularis Leaf and Their Antioxidant, Anti-Inflammatory and Anti-Elastase Properties

Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis, molecular docking, and enzyme inhibitory kinetics

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