New 2-amino-pyridinyl-N-acylhydrazones: Synthesis and identification of their mechanism of anti-inflammatory action

Cordeiro, Natália de Morais; Freitas, Rosana Helena C. N.; Fraga, Carlos A.M.; Fernandes, Patrícia Dias

doi:10.1016/j.biopha.2019.109739

Cited by 11 publications

(12 citation statements)

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“…[42] Furthermore, 2-amino-pyridinyl-N-acylhydrazones have also been reported as anti-inflammatory agents showing p38α MAP kinase inhibitory activity. [43] Motivated by the aforementioned findings, and in the course of research work in our lab on heterocyclic compounds, [44][45][46][47][48] we synthesized bicyclic quinoxaline derivatives bearing a hydrazone moiety (Figure 1). The synthesized compounds were evaluated for anti-inflammatory and p38α MAP kinase inhibitory activities as well as lipid peroxidation and ulcerogenicity.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, biological evaluation, and in silico studies of quinoxaline derivatives as potent p38α MAPK inhibitors

Anjali,

Kamboj,

Alam

et al. 2023

Archiv der Pharmazie

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A new series of quinoxaline derivatives possessing the hydrazone moiety were designed, synthesized, and screened for in‐vitro anti‐inflammatory activity by the bovine serum albumin (BSA) denaturation technique, and for antioxidant activity, by the (2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay. The synthesized compounds were also tested for p38α mitogen‐activated protein (MAP) kinase inhibition. The in‐vivo anti‐inflammatory activity was assessed by the carrageenan‐induced rat paw edema inhibition method. All the compounds (4a–n) exhibited moderate to high in‐vitro anti‐inflammatory activity. Compound 4a displayed the highest inhibitory activity in the BSA assay (83.42%) in comparison to the standard drug diclofenac sodium (82.90%), while 4d exhibited comparable activity (81.87%). The DPPH assay revealed that compounds 4a and 4d have free radical scavenging potential (74.70% and 74.34%, respectively) comparable to the standard butylated hydroxyanisole (74.09%). Furthermore, the p38α MAP kinase inhibition assay demonstrated that compound 4a is highly selective against p38α MAP kinase (IC50 = 0.042) in comparison to the standard SB203580 (IC50 = 0.044). The five most active compounds (4a–4d and 4f) with good in‐vitro profiles were selected for in‐vivo anti‐inflammatory studies. Compounds 4a and 4d were found to display the highest activity (83.61% and 82.92% inhibition, respectively) in comparison to the standard drug diclofenac sodium (82.65% inhibition). These compounds (4a and 4d) also exhibited better ulcerogenic and lipid peroxidation profiles than diclofenac sodium. The molecular docking and molecular dynamics simulation studies were also performed and found to be in agreement with the p38α MAP kinase inhibitory activity.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, biological evaluation, and in silico studies of quinoxaline derivatives as potent p38α MAPK inhibitors

Anjali,

Kamboj,

Alam

et al. 2023

Archiv der Pharmazie

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“…The N -acylhydrazone (NAH) moiety is one of the most extensively studied privileged structures in medicinal chemistry nowadays. This substructure is present in a great number of potent compounds with various pharmacological activities such as anticancer, antimicrobial, antiviral, anti-platelet, antinociceptive, and anti-inflammatory [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. It should be noted that N -acylhydrazone derivatives can affect different molecular targets and signaling pathways associated with inflammatory disorders.…”

Section: Introductionmentioning

confidence: 99%

“…The complex and wide-range anti-inflammatory effect of N -acylhydrazones can be explained by the relative acidity of the amide hydrogen and its ability to stabilize free radicals. Therefore, the NAH group can imitate the bis-allylic moiety of PUFAs such as AA [ 23 , 24 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Biological, Spectroscopic and Computational Investigations of Novel N-Acylhydrazone Derivatives of Pyrrolo[3,4-d]pyridazinone as Dual COX/LOX Inhibitors

Mikus,

Świątek,

Przybyła

et al. 2023

Molecules

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Secure and efficient treatment of diverse pain and inflammatory disorders is continually challenging. Although NSAIDs and other painkillers are well-known and commonly available, they are sometimes insufficient and can cause dangerous adverse effects. As yet reported, derivatives of pyrrolo[3,4-d]pyridazinone are potent COX-2 inhibitors with a COX-2/COX-1 selectivity index better than meloxicam. Considering that N-acylhydrazone (NAH) moiety is a privileged structure occurring in many promising drug candidates, we decided to introduce this pharmacophore into new series of pyrrolo[3,4-d]pyridazinone derivatives. The current paper presents the synthesis and in vitro, spectroscopic, and in silico studies evaluating the biological and physicochemical properties of NAH derivatives of pyrrolo[3,4-d]pyridazinone. Novel compounds 5a-c–7a-c were received with high purity and good yields and did not show cytotoxicity in the MTT assay. Their COX-1, COX-2, and 15-LOX inhibitory activities were estimated using enzymatic tests and molecular docking studies. The title N-acylhydrazones appeared to be promising dual COX/LOX inhibitors. Moreover, spectroscopic and computational methods revealed that new compounds form stable complexes with the most abundant plasma proteins–AAG and HSA, but do not destabilize their secondary structure. Additionally, predicted pharmacokinetic and drug-likeness properties of investigated molecules suggest their potentially good membrane permeability and satisfactory bioavailability.

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“…The N-acylhydrazonic derivative JR19 namely N-(1H-indol-3yl) methylene-2-cyanoacetrohydrazide has been investigated for its antioxidant [ 21 ], antifungal [ 22 ], antimicrobial [ 23 ] and anti-inflammatory activities [ 21 , 24 , 25 ]. Therefore, JR19 seems to be a promising candidate to be incorporated into cellulose acetate films, especially when the pharmacological application is directed towards the skin.…”

Section: Introductionmentioning

confidence: 99%

N-acylhydrazone Derivative-Loaded Cellulose Acetate Films: Thermoanalytical, Spectroscopic, Mechanical and Morphological Characterization

et al. 2021

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Cellulose acetate (ACT) is one of the most important cellulose derivatives due to its biodegradability and low toxicity, presenting itself as one of the main substitutes for synthetic materials in the development of wound dressing films. The incorporation of a N-acylhydrazonic derivative (JR19), with its promising anti-inflammatory activity, may represent an alternative for the treatment of skin wounds. This work aims to develop and to physicochemically and mechanically characterize ACT films containing JR19. The films were prepared using the ‘casting’ method and further characterized by thermoanalytical and spectroscopic techniques. In addition, mechanical tests and morphological analysis were performed. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to excipients and films were similar, indicating the absence of physical incompatibilities between ACT and JR19. Infrared spectroscopy showed that JR19 was incorporated into ACT films. The characteristic band attributed to C≡N (2279 to 2264 cm−1) was observed in the spectra of JR19, in that of the physical mixture of JR19/ACT, and, to a lesser extent, in the spectra of JR19 incorporated into the ACT film, suggesting some interaction between JR19 and ACT. X-ray diffraction (XRD) evidenced the suppression of the crystallinity of JR19 (diffraction peaks at 8.54°, 12.80°, 14.09°, 16.08°, 18.19°, 22.65°, 23.59°, 24.53°, 25.70°, 28.16° and 30.27°2θ) after incorporation into ACT films. The mechanical tests indicated the adequate integrity of the films and their resistance to bending. The morphological characterization showed JR19 crystals along with a homogeneously distributed porous structure throughout the surface of the films with an average diameter of 21.34 µm and 22.65 µm of the films alone and of those incorporating JR19F, respectively. This study was able to characterize the ACT films incorporating JR19, showing their potential to be further developed as wound healing dressings.

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New 2-amino-pyridinyl-N-acylhydrazones: Synthesis and identification of their mechanism of anti-inflammatory action

Cited by 11 publications

References 50 publications

Design, synthesis, biological evaluation, and in silico studies of quinoxaline derivatives as potent p38α MAPK inhibitors

Design, synthesis, biological evaluation, and in silico studies of quinoxaline derivatives as potent p38α MAPK inhibitors

Synthesis, Biological, Spectroscopic and Computational Investigations of Novel N-Acylhydrazone Derivatives of Pyrrolo[3,4-d]pyridazinone as Dual COX/LOX Inhibitors

N-acylhydrazone Derivative-Loaded Cellulose Acetate Films: Thermoanalytical, Spectroscopic, Mechanical and Morphological Characterization

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