5-Fluorouracil (5-FU)-based Aza-Michael addition product: A selective carbonic anhydrase IX inhibitor

Mushtaque, Md.; Avecilla, Fernando; Ahmad, Irfan; Alharbi, Ahmed; Κhan, Parvez; Ahamad, Shahzaib; Hassan, Imtaiyaz

doi:10.1016/j.molstruc.2021.129977

Cited by 8 publications

(4 citation statements)

References 38 publications

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“…The equilibration of the systems was carried out in the canonical ensemble (NVT for 500 ps at 300 K using Berendsen thermostat), while for production, the isothermal-isobaric ensemble was assessed (NPT for 500 ps at 1 bar using Parrinello-Rahman barostat) [85]. Particle Mesh Ewald (PME) method was used for the long-range electrostatic forces [85,86].…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives

Pele,

Marc,

Mogoșan

et al. 2024

Molecules

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Two series, “a” and “b”, each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABAA receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D1–3 = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABAA receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABAA receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, 1a–9a and 1b–9b, present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the “b” series, particularly for compound 8b.

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Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives

Pele,

Marc,

Mogoșan

et al. 2024

Molecules

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“…Therefore, they also require activation by deprotonation. As deprotonating agent sodium hydride [93] or organic bases like TEA [94] or DBU [95] are applied. Uracil salt generated in situ undergos the conjugate nucleophilic addition to various Michael acceptors in polar solvent (DMF, DMSO).…”

Section: Amides Carbamates Hydrazides and Uracilesmentioning

confidence: 99%

Weak Nucleophiles in the Aza‐Michael Reaction

Rulev

2023

Adv Synth Catal

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The 1,4‐conjugated addition of nitrogen centered nucleophiles to electron‐deficient alkenes is one of the most significant and widely used reactions in modern synthetic organic chemistry. To date, various protocols for the aza‐Michael reaction have been developed. However, these reports mainly focus on the use of strong Michael donors. In recent years, the conjugate addition of weak nitrogen nucleophiles to various Michael acceptors gained increasing popularity. Impressive progress in this area has been achieved by the use of more efficient catalyst systems. This review aims to provide a critical analysis of the results obtained in reactions of weak nucleophiles (azoles, pyrroles, indoles, carbamates, purines, amides, hydrazides, uraciles etc) with electron‐deficient alkenes which were reported over the past twelve years.

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“…The Michael reaction is a versatile synthesis type for linking electron-poor olefins to a wide range of nucleophiles [ 18 ]. Enolates [ 19 , 20 ], nitrogen-containing [ 21 , 22 , 23 , 24 , 25 , 26 ] reagents, and thiols [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ] are typical Michael donors, while alkyl acrylates are mainly used as Michael acceptors [ 33 ]. Adding an enolate anion to the α,β-unsaturated carbonyl compound to form a carbon–carbon bond is a Michael reaction [ 19 , 20 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…A type of polymerization for the addition of hydroxyl monomers with electrophilic double or triple bonds is called the oxa-Michael reaction [ 35 , 36 ]. In the case of nitrogen and sulphur-containing donors, the reaction is called aza-Michael [ 21 , 22 , 23 , 24 , 25 , 26 , 37 ] and thio-Michael [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ] addition reactions, respectively. In recent years, aza- and thio-Michael reactions have gained attention for polymerization [ 35 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Bio-Based Polymer Developments from Tall Oil Fatty Acids by Exploiting Michael Addition

et al. 2022

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In this study, previously developed acetoacetates of two tall-oil-based and two commercial polyols were used to obtain polymers by the Michael reaction. The development of polymer formulations with varying cross-link density was enabled by different bio-based monomers in combination with different acrylates—bisphenol A ethoxylate diacrylate, trimethylolpropane triacrylate, and pentaerythritol tetraacrylate. New polymer materials are based on the same polyols that are suitable for polyurethanes. The new polymers have qualities comparable to polyurethanes and are obtained without the drawbacks that come with polyurethane extractions, such as the use of hazardous isocyanates or reactions under harsh conditions in the case of non-isocyanate polyurethanes. Dynamic mechanical analysis, differential scanning calorimetry, thermal gravimetric analysis, and universal strength testing equipment were used to investigate the physical and thermal characteristics of the created polymers. Polymers with a wide range of thermal and mechanical properties were obtained (glass transition temperature from 21 to 63 °C; tensile modulus (Young’s) from 8 MPa to 2710 MPa and tensile strength from 4 to 52 MPa). The synthesized polymers are thermally stable up to 300 °C. The suggested method may be used to make two-component polymer foams, coatings, resins, and composite matrices.

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5-Fluorouracil (5-FU)-based Aza-Michael addition product: A selective carbonic anhydrase IX inhibitor

Cited by 8 publications

References 38 publications

Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives

Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives

Weak Nucleophiles in the Aza‐Michael Reaction

Bio-Based Polymer Developments from Tall Oil Fatty Acids by Exploiting Michael Addition

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