Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles

Guglielmi, Paolo; Carradori, Simone; Poli, Giulio; Secci, Daniela; Cirilli, Roberto; Rotondi, Giulia; Chimenti, Paola; Petzer, Anél; Petzer, Jacobus P.

doi:10.3390/molecules24030484

Cited by 24 publications

(15 citation statements)

References 35 publications

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“…In this work, DCH/CO-RMs presenting different “drug spheres” are reported. Ten compounds were synthesized according to the general procedure reported in Figure 1 and Figure 2 based on procedures published in our previous works [ 41 , 42 , 43 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

Dual Carbonic Anhydrase IX/XII Inhibitors and Carbon Monoxide Releasing Molecules Modulate LPS-Mediated Inflammation in Mouse Macrophages

et al. 2021

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Low concentrations of carbon monoxide (CO) were reported to exhibit anti-inflammatory effects when administered in cells by suitable chemotypes such as CO releasing molecules (CO-RMs). In addition, the pH-modulating abilities of specific carbonic anhydrase isoforms played a crucial role in different models of inflammation and neuropathic pain. Herein, we report a series of chemical hybrids consisting of a Carbonic Anhydrase (CA) inhibitor linked to a CO-RM tail (CAI/CO-RMs). All compounds and their precursors were first tested in vitro for their inhibition activity against the human CA I, II, IX, and XII isoforms as well their CO releasing properties, aiming at corroborating the data by means of molecular modelling techniques. Then, their impact on metabolic activity modulation of RAW 264.7 mouse macrophages for 24 and 48 h was assessed with or without lipopolysaccharide (LPS) stimulation. The compounds were shown to counteract the inflammatory stimulus as also indicated by the reduced tumor necrosis factor alpha (TNF-α) release after treatment. All the biological results were compared to those of N-acetylcysteine (NAC) as a reference antioxidant compound. Within the series, two CAI/CO-RM hybrids (1 and 2), bearing both the well-known scaffold able to inhibit CAs (acesulfame) and the cobalt-based CO releasing portion, induced a higher anti-inflammatory effect up to 48 h at concentrations lower than NAC.

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Section: Resultsmentioning

confidence: 99%

Dual Carbonic Anhydrase IX/XII Inhibitors and Carbon Monoxide Releasing Molecules Modulate LPS-Mediated Inflammation in Mouse Macrophages

et al. 2021

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“…Pyrazolines are reduced pyrazoles, and several studies have shown these chiral molecules have remarkable MAO inhibitory properties (Figure ). Recently, Ucar et al synthesized some 1‐ N ‐substituted thiocarbamoyl‐3‐phenyl‐5‐thienyl‐2‐pyrazoline derivatives and reported compound 35 selectively inhibited AChE (IC 50 = 0.09 µM) and MAO‐B (IC 50 = 43 µM).…”

Section: Overview Of Dual‐acting Mao and Che Inhibitorsmentioning

confidence: 99%

Emerging therapeutic potentials of dual‐acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases

Mathew

Parambi

Mathew³

et al. 2019

Archiv der Pharmazie

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No drug has been approved to prevent neuronal cell loss in patients suffering from Parkinson's disease (PD) or Alzheimer's disease (AD); despite increased comprehension of the underlying molecular causes, therapies target cognitive functional improvement and motor fluctuation control. Drug design strategies that adopt the "one protein, one target" philosophy fail to address the multifactorial aetiologies of neurodegenerative disorders such as AD and PD optimally. On the contrary, restoring neurotransmitter levels by combined combinatorial inhibition of cholinesterases, monoamine oxidases, and adenosine A 2A A receptors, in conjunction with strategies to counter oxidative stress and beta-amyloid plaque accumulation, would constitute a therapeutically robust, multitarget approach. This extensive review delineates the therapeutic advantages of combining dual-acting molecules that inhibit monoamine oxidases and cholinesterases and/or adenosine A 2A A receptors, and describes the structure-activity relationships of compound classes that include, but are not limited to, alkaloids, coumarins, chalcones, donepezil-propargylamine conjugates, homoisoflavonoids, resveratrol analogs, hydrazones, and pyrazolines. In the wake of recent advances in network biology, in silico approaches, and omics, this review emphasizes the need to consider conceptually informed research strategies for drug discovery, in the context of the mounting burden posed by chronic neurodegenerative diseases with complex aetiologies and pathophysiologies involving multiple signalling pathways and numerous drug targets. K E Y W O R D Sacetylcholinesterase, adenosine antagonist, monoamine oxidase, multitarget

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“…Different pyrazoline derivatives were synthesized and screened for their MAO inhibitory activities. Especially, substitution at 1, 3, and 5 positions of the pyrazoline nucleus displayed a significant activity towards MAO enzyme . There are also many thiazole compounds found to be effective against MAO enzymes in the literature …”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of new pyrazoline‐thiazole derivatives as monoamine oxidase inhibitors

Çevik

Osmaniye

Sağlık

et al. 2019

Journal of Heterocyclic Chem

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A novel series of 1,3,5‐trisubstituted‐2‐pyrazoline derivatives (4a‐4k) was synthesized and their chemical structures characterized by 1H NMR, 13C NMR, and mass spectroscopy. These compounds were evaluated as inhibitors for of type A and type B monoamine oxidase (MAO) enzymes. The most common inhibitors of MAO enzymes used to treat depression and anxiety such as selegiline and moclobemide drugs were used as reference agents. A result of biological evaluation of these compounds revealed compounds 4c, 4d, and 4ı as potent and selective MAO A inhibitors. The most active compound 4ı, which is 2,4‐dimethoxy at phenyl ring, showed strong inhibitory activity at MAO A (IC50 of 0.0445 ± 0.0018μM). Furthermore, compounds 4c and 4d showed significant inhibition profile on MAO A with the IC50 values 0.1423 ± 0.0051μM and 0.2148 ± 0.0067μM, respectively.

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Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles

Cited by 24 publications

References 35 publications

Dual Carbonic Anhydrase IX/XII Inhibitors and Carbon Monoxide Releasing Molecules Modulate LPS-Mediated Inflammation in Mouse Macrophages

Dual Carbonic Anhydrase IX/XII Inhibitors and Carbon Monoxide Releasing Molecules Modulate LPS-Mediated Inflammation in Mouse Macrophages

Emerging therapeutic potentials of dual‐acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases

Synthesis and evaluation of new pyrazoline‐thiazole derivatives as monoamine oxidase inhibitors

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