Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Ventura, Tiziano De; Perrone, Mariasole; Missiroli, Sonia; Pinton, Paolo; Marchetti, Paolo; Strazzabosco, Giovanni; Turrin, Giulia; Illuminati, Davide; Cristofori, Virginia; Fantinati, Anna; Fabbri, Massimo; Giorgi, Carlotta; Trapella, Claudio; Zanirato, Vinicio

doi:10.3390/ijms23168957

Cited by 4 publications

(4 citation statements)

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“…These results have indicated that the studied chalcones inhibit the canonical and non-canonical pathways of the NLRP3 inflammasome [ 264 ]. The naturally occurring chalcone veluton F and some of its regioisomers have also exhibited NLRP3 inflammasome inhibitory activity by inhibiting the release of IL-1β in both in vitro cell systems and in vivo animal models [ 265 ].…”

Section: Animal Studiesmentioning

confidence: 99%

Chalcones and Gastrointestinal Cancers: Experimental Evidence

Michalková

Kello

Čižmáriková

et al. 2023

IJMS

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Colorectal (CRC) and gastric cancers (GC) are the most common digestive tract cancers with a high incidence rate worldwide. The current treatment including surgery, chemotherapy or radiotherapy has several limitations such as drug toxicity, cancer recurrence or drug resistance and thus it is a great challenge to discover an effective and safe therapy for CRC and GC. In the last decade, numerous phytochemicals and their synthetic analogs have attracted attention due to their anticancer effect and low organ toxicity. Chalcones, plant-derived polyphenols, received marked attention due to their biological activities as well as for relatively easy structural manipulation and synthesis of new chalcone derivatives. In this study, we discuss the mechanisms by which chalcones in both in vitro and in vivo conditions suppress cancer cell proliferation or cancer formation.

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Section: Animal Studiesmentioning

confidence: 99%

Chalcones and Gastrointestinal Cancers: Experimental Evidence

Michalková

Kello

Čižmáriková

et al. 2023

IJMS

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“…Compounds 6c , 7n , and 10 displayed low nanomolar potency in both models (Figure B). Of note, in THP-1 cells, the isoquinoline derivative 7n (IC 50 = 5.36 nM) and the tyrosine derivative 10 (IC 50 = 3.29 nM) were shown to be even more potent than the positive control MCC950 (IC 50 : 8.1 nM in human monocyte-derived macrophages as reported in ref ).…”

Section: Resultsmentioning

confidence: 99%

“…These findings prompted the development of potent and selective NLRP3 inhibitors that are extensively used as pharmacological tools to elucidate possible clinical applications of NLRP3 targeting strategies. , In this rapidly expanding research field, numerous compounds are already under preclinical investigation, and few of them have reached phase I/II clinical trials. − Among these, MCC950 ( 1 , Figure ) is the most studied NLRP3 inhibitor after its early discovery in 2003 . MCC950 was shown to block canonical and noncanonical NLRP3 activation at nanomolar concentrations in vitro with high selectivity over AIM2, NLRC4, or NLRP1 inflammasomes .…”

Section: Introductionmentioning

confidence: 99%

Novel Aryl Sulfonamide Derivatives as NLRP3 Inflammasome Inhibitors for the Potential Treatment of Cancer

et al. 2023

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The NLRP3 inflammasome is a critical component of innate immunity that senses diverse pathogen-and host-derived molecules. However, its aberrant activation has been associated with the pathogenesis of multiple diseases, including cancer. In this study, we designed and synthesized a series of aryl sulfonamide derivatives (ASDs) to inhibit the NLRP3 inflammasome. Among these, compounds 6c, 7n, and 10 specifically inhibited NLRP3 activation at nanomolar concentrations without affecting the activation of the NLRC4 and AIM2 inflammasomes. Furthermore, we demonstrated that these compounds reduce interleukin-1β (IL-1β) production in vivo and attenuate melanoma tumor growth. Moreover, metabolic stability in liver microsomes of 6c, 7n, and 10 was studied along with plasma exposure in mice of the most interesting compound 6c. Therefore, we generated potent NLRP3 inflammasome inhibitors, which can be considered in future medicinal chemistry and pharmacological studies aimed at developing a new therapeutic approach for NLRP3 inflammasome-driven cancer.

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“…Accordingly, different NLRP3 in ammasome inhibitors have been reported to date, including the ones that directly inhibit the NLRP3 and those that act on its related signaling pathways [10]. Indeed, recently we identi ed a series of aryl sulfonamide derivatives (ASDs) and natural compounds with high potency and selectivity in inhibiting NLRP3 activation in vitro and in vivo [11,12]. Among all the cited inhibitors, nutraceutical compounds might be of high impact for their low side effects in prolonged treatments.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia.

Vezzani,

Perrone,

Carinci

et al. 2023

Preprint

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Introduction: The recent pandemic outbursts, due to SARS-CoV-2, has highlighted once more the central role of the inflammatory process in the propagation of viral infection. In fact, the main consequence of COVID-19 is the induction of a diffuse pro-inflammatory state, also defined as cytokine storm, that affects different organs, but mostly the lungs. Therefore, despite the progress in the vaccination campaign, the high mutability of this virus also requires effective pharmaceutical approaches aimed to reduce the inflammatory spread. Methods The effect of SARS-CoV-2 infection on IL-1β and IL-6 levels was assessed by performing ELISA on patients' serum and stimulated-PBMCs. The therapeutic potential of cinnamaldehyde on COVID-19 was evaluated in vitro, testing the effects on THP-1 macrophages' inflammatory state, and on the viral replication in Calu-3 and Vero6 cells. Moreover, we assessed the effect of cinnamaldehyde also in vivo generating a lung-inflammatory model by intranasal administration of LPS. Results In this study we highlight that COVID-19 patients have higher IL-1β and IL-6 plasma levels compared to non-COVID-19 pneumonia patients, showing that human mononuclear cells (PBMCs) isolated from SARS-CoV-2 infected patients are more prone to release pro-inflammatory cytokines upon stimuli. Furthermore, we demonstrated how cinnamaldehyde, a natural compound easily tolerated by the majority of human beings, significantly reduces SARS-CoV-2-related inflammation by inhibiting IL-1β release by macrophages, and viral replication in epithelial cells. In addition, we confirmed the ability of aerosol-administered cinnamaldehyde to in vivo reduce IL-1β release in a lung-inflammatory model. Conclusion The obtained results suggest the possible use of cinnamaldehyde suitable as a co-adjuvant preventive treatment for COVID-19 disease together with vaccination, but also as a promising dietary supplement to reduce, more broadly, viral induced inflammation.

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Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

Cited by 4 publications

References 50 publications

Chalcones and Gastrointestinal Cancers: Experimental Evidence

Chalcones and Gastrointestinal Cancers: Experimental Evidence

Novel Aryl Sulfonamide Derivatives as NLRP3 Inflammasome Inhibitors for the Potential Treatment of Cancer

SARS-CoV-2 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia.

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