Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors

Arias, Fabio; Franco-Montalbán, Francisco; Romero, Miguel; Carriòn, María Dora; Camacho, M. Encarnación

doi:10.1016/j.bmc.2021.116294

Cited by 16 publications

(12 citation statements)

References 42 publications

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“…Docking results (Table 2) of compounds 1-8 at active site of iNOS had binding energy ranging from À6.43 kcal mol À1 to À8.00 kcal mol À1 which are close with that of positive drug S71 (binding energy À7.71 kcal mol À1 ). 21 In the interaction with TNF-a protein, compounds 1-8 exhibited a bit weak binding affinity to active site (À6.15 kcal mol À1 to À7.81 kcal mol À1 ) in comparison with positive drug 307 (binding energy À8.62 kcal mol À1 ). 22 However, compounds 1-8 exhibited unstable binding to active site of COX-2 (positive binding energy, from +16.60 kcal mol À1 to +90.84 kcal mol À1 ) as expected to positive drug celecoxib (binding energy À11.12 kcal mol À1 ).…”

Section: Resultsmentioning

confidence: 98%

“…aOriginal inhibitors S71, 307, and celecoxib were used to be positive drugs and locate active site of iNOS (), TNF-α (), and COX-2 () proteins. 21–23 …”

Section: Resultsmentioning

confidence: 99%

“…Molecular docking was carried out using AutoDock v4.2 program as previously described. [21][22][23][24] The crystal structure of inducible nitric oxide synthase with inhibitor (S71), TNF-a with inhibitor (307), and COX-2 with inhibitor (celecoxib) were obtained from the RCSB Protein Database Bank (PDB ID: 4CX7, 2AZ5, and 3LN1, respectively). The 3D structures of compounds 1-8 were obtained by Spartan18 soware.…”

Section: Molecular Dockingmentioning

confidence: 99%

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New dibenzocyclooctadiene lignans from Kadsura induta with their anti-inflammatory activity

et al. 2022

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Section: Resultsmentioning

confidence: 98%

“…aOriginal inhibitors S71, 307, and celecoxib were used to be positive drugs and locate active site of iNOS (), TNF-α (), and COX-2 () proteins. 21–23 …”

Section: Resultsmentioning

confidence: 99%

Section: Molecular Dockingmentioning

confidence: 99%

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New dibenzocyclooctadiene lignans from Kadsura induta with their anti-inflammatory activity

et al. 2022

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“…In contrast, the standard ligand in Figure 4 only formed a hydrogen bond in the GLU 597 residue. Since GLU 597 is a catalytic residue directly involved in the catalyzed reaction, the specific bond on that residue needs to be considered [31]. Furthermore, the gallic acid 4-O-(6-galloyl glucoside) produced more hydrogen bonds than the standard ligand, leading to higher conformational stability when interacting with the nNOS receptor.…”

Section: Gallic Acid and Its Derivatives As Nnos Inhibitorsmentioning

confidence: 99%

Molecular Docking of Gallic Acid and Its Derivatives as the Potential nNOS Inhibitors

et al. 2022

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The global prevalence of anxiety and depression rates have increased by 25% due to the impact of the COVID-19 pandemic. Depression can occur due to an increase in NO produced by the nNOS enzyme. Gallic acid and its derivatives can be obtained from nature and have various biological activities. This study aimed to determine the potential of gallic acid and its derivatives as nNOS inhibitors using the molecular docking method with parameters of binding energy values, RMSD values, and specific binding to amino acid residues. The results showed that gallic acid, 4-O-methyl gallic acid, and epigallocatechin gallate had bond energies of −1.87; −2.36; and −0.12 kcal/mol, respectively. Compared to the standard ligand, which had binding energy of −2.84 kcal/mol, gallic acid 4-O-(6-galloyl glucoside) had binding energy of −4.12 kcal/mol. Based on these results, gallic acid 4-O-(6-galloyl glucoside) can potentially inhibit nNOS.

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“…Амідини з трихлорометильною групою проявляють властивості інотропних агентів [1]. Функціоналізовані амідини проявляють протиракову [2][3][4] та антидіабетичну [5] активність, їх досліджено як антигіпертензивні [6], протипаразитарні [7,8] засоби, використовують як скафолди в синтезі аза-гетероциклів та ліганди для комплексоутворення [9,10]. Тому синтез нових функціональних похідних таких амідинів є, безумовно, актуальним завданням.…”

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Synthesis of Salts of N-Allyltrichloroacetamidinium Hexahalogenotellurate

et al. 2022

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Amidines with a trichloromethyl group exhibit the properties of inotropic agents, which are used as scaffolds in synthesizing aza-heterocycles and ligands for complex formation. Functionalized amidines show anticancer, and antidiabetic activity, and are antihypertensive and antiparasitic agents. The synthesis of new functional derivatives of such amidines is definitely an urgent task. The introduction of an alkenyl substituent and several nucleophilic centers in the amidine creates prerequisites for electrophilic cyclization. This work aims to study the reactions of N-allyl-N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide with tellurium halides. The starting N-allyl-N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide was synthesized from N-allyl-N-methyl-2,2,2-trichloroethanimidamide by the action of trimethylsilyl chloride in the presence of triethylamine base. The reaction of N-allyl-N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide with tellurium dioxide in hydrohalic acid was carried out while cooling to 0°C. Elemental analysis confirms that the electrophilic reagent is in its acidic form in the complex. The 1H NMR spectra of the obtained complexes indicate the absence of EVC - the spin pattern of the proton signals of the allylic substituent, characteristic of the starting compounds, is preserved, but the signals are shifted by 0.3–0.6 ppm. The absence of proton signals of the trimethyl salt substituent indicates the removal of imide protection under these conditions. The presence of a broadened singlet in a weak field indicates the presence of acidic protons. Apparently, protonation does not take place on the alkenyl multiple bonds, but, presumably, on the imide nitrogen atom. Based on elemental analysis, the composition of the formed complex was determined: N-allyl-N-methyl-2,2,2-trichloroethanimidamidine: hexahalogenotelluric acid as 1:0.5, which contains 4 or 3 water molecules. So the interaction of N-allyl-N-methyl-N'-(trimethylsilyl)-2,2,2-trichloroethanimidamide with tellurium tetrahalides in a strongly acidic environment, tellurium- or proton-induced cyclization does not occur, but hexahalogenotellurate N-allyl-N-methyl-2,2,2-trichloroethaneimidamidinium regardless of the polarity of the solvent.

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Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors

Cited by 16 publications

References 42 publications

New dibenzocyclooctadiene lignans from Kadsura induta with their anti-inflammatory activity

New dibenzocyclooctadiene lignans from Kadsura induta with their anti-inflammatory activity

Molecular Docking of Gallic Acid and Its Derivatives as the Potential nNOS Inhibitors

Synthesis of Salts of N-Allyltrichloroacetamidinium Hexahalogenotellurate

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