Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies

Zang, Yingda; Lai, Fangfang; Fu, Junmin; Li, Chuang‐Jun; Ma, Jie; Chen, Chengjuan; Liu, Ke; Zhang, Tiantai; Chen, Xiaoguang; Zhang, Dongming

doi:10.1016/j.ejmech.2020.112079

Cited by 18 publications

(12 citation statements)

References 27 publications

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“…Several studies have reported that natural products derived from medicinal plants exert significant anti-inflammatory activities and suppress the NF-kB signalling pathway, which are potential resources of anti-inflammatory candidates (30)(31)(32)(33)(34)(35)(36)(37)(38). In this study, we discovered and characterized a novel isoquinoline alkaloid LA that possesses an unusual C-1 methyl and a N!O group, from a medicinal plant L. cubeba that is widely used for the treatment of inflammatory diseases (9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

et al. 2021

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Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1β. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.

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Section: Discussionmentioning

confidence: 99%

Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

et al. 2021

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“…Zhang et al obtained novel nitric oxide-releasing derivatives of triptolide [ 131 ]. Triptolide was first isolated from Tripterygium wilfordii Hak.…”

Section: The Most Potent Anti-melanoma Agent From Most Recent Studies...mentioning

confidence: 99%

“…Further studies involving a xenograft mouse model of melanoma established by the subcutaneous inoculation of B16F10 showed that the proposed compound inhibited the growth of melanoma at low doses (0.3 mg/kg). Moreover, the SAR study indicated that the length of the linker connecting the furoxan ring with the triptolide scaffold is inversely proportional to the activity [ 131 ].…”

Section: The Most Potent Anti-melanoma Agent From Most Recent Studies...mentioning

confidence: 99%

New Potential Agents for Malignant Melanoma Treatment—Most Recent Studies 2020–2022

Kozyra

Krasowska

Pitucha

2022

IJMS

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Malignant melanoma (MM) is the most lethal skin cancer. Despite a 4% reduction in mortality over the past few years, an increasing number of new diagnosed cases appear each year. Long-term therapy and the development of resistance to the drugs used drive the search for more and more new agents with anti-melanoma activity. This review focuses on the most recent synthesized anti-melanoma agents from 2020–2022. For selected agents, apart from the analysis of biological activity, the structure–activity relationship (SAR) is also discussed. To the best of our knowledge, the following literature review delivers the latest achievements in the field of new anti-melanoma agents.

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“…NO-releasing STAT3 inhibitors showed antiproliferative activity in A375 melanoma cells carrying the BRAFV600E mutation via reactive oxygen species production and G1 cell cycle arrest [ 350 ]. Other NO-releasing agents have also been researched, acting as a successful anti-inflammatory and antitumoral agents, both in vivo and in vitro [ 351 ].…”

Section: Cellular and Molecular Neuro-immune Interactions In Melanomamentioning

confidence: 99%

Neuroendocrine Factors in Melanoma Pathogenesis

Scheau

Drăghici

Ilie

et al. 2021

Cancers

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Melanoma is one of the most aggressive skin cancers with a sharp rise in incidence in the last decades, especially in young people. Recognized as a significant public health issue, melanoma is studied with increasing interest as new discoveries in molecular signaling and receptor modulation unlock innovative treatment options. Stress exposure is recognized as an important component in the immune-inflammatory interplay that can alter the progression of melanoma by regulating the release of neuroendocrine factors. Various neurotransmitters, such as catecholamines, glutamate, serotonin, or cannabinoids have also been assessed in experimental studies for their involvement in the biology of melanoma. Alpha-MSH and other neurohormones, as well as neuropeptides including substance P, CGRP, enkephalin, beta-endorphin, and even cellular and molecular agents (mast cells and nitric oxide, respectively), have all been implicated as potential factors in the development, growth, invasion, and dissemination of melanoma in a variety of in vitro and in vivo studies. In this review, we provide an overview of current evidence regarding the intricate effects of neuroendocrine factors in melanoma, including data reported in recent clinical trials, exploring the mechanisms involved, signaling pathways, and the recorded range of effects.

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Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies

Cited by 18 publications

References 27 publications

Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

New Potential Agents for Malignant Melanoma Treatment—Most Recent Studies 2020–2022

Neuroendocrine Factors in Melanoma Pathogenesis

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