Synthesis and pharmacological evaluation of novel limonin derivatives as anti-inflammatory and analgesic agents with high water solubility

Yang, Yu-Chu; Wang, Xinhui; Zhu, Qihua; Gong, Guoqing; Luo, Danmeng; Jiang, Aidou; Yang, Liyan; Xu, Yungen

doi:10.1016/j.bmcl.2014.02.003

Cited by 39 publications

(37 citation statements)

References 19 publications

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“…The unbalanced solubility profile of the latter may explain the relatively low number of studies on their respective biological activities which are hampered by difficult isolation from natural sources and poor pharmacokinetics. Analgesic [45], anticancer [46][47][48][49][50][51][52][53][54][55][56][57][58][59], anti-inflammatory [45,[60][61][62], antibacterial [63,64], antioxidant [4,65,66], antiviral [67], larvicidal [68,69] Anticancer [46,47,58,59,70], anti-hyperglycemic [71], anti-inflammatory [25,62], antioxidant [4,65,66], antiviral [67], larvicidal [68,69] …”

Section: Chemistry and Classificationsmentioning

confidence: 99%

“…A series of limonin (1) and deoxylimonin (10) oxime derivatives of the general structure 37 ( Figure 7) were obtained through an oxime derivatization procedure, and subsequently evaluated as anti-inflammatory (ear swelling induced by xylene test in mice) and analgesic (acetic acid-induced writhing and tail-immersion tests in mice) agents [45]. In this case, tertiary amine moieties were introduced onto C-7 position in order to obtain water-soluble derivatives, possibly endowed with higher bioavailabilities than those displayed by the parent CLs 1 and 10.…”

mentioning

confidence: 99%

“…The most interesting compound was the limonin derivative bearing an O-diethylaminoethyl side chain (38) since it was more potent than acetylsalicylic acid and naproxen in the analgesic and the anti-inflammatory assays, respectively. writhing and tail-immersion tests in mice) agents [45]. In this case, tertiary amine moieties were introduced onto C-7 position in order to obtain water-soluble derivatives, possibly endowed with higher bioavailabilities than those displayed by the parent CLs 1 and 10.…”

mentioning

confidence: 99%

“…Incidentally, the higher resistance of Caco-2 cells may be related to high expression of the ABC transporter P-gp [3,51], an efflux pump that impedes cytoplasmic accumulation of lipophilic compounds. writhing and tail-immersion tests in mice) agents [45]. In this case, tertiary amine moieties were introduced onto C-7 position in order to obtain water-soluble derivatives, possibly endowed with higher bioavailabilities than those displayed by the parent CLs 1 and 10.…”

mentioning

confidence: 99%

“…Water-soluble analogs of limonin (1); and deoxylimonin (10) endowed with analgesic and anti-inflammatory properties [45].…”

mentioning

confidence: 99%

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The Chemistry and Pharmacology of Citrus Limonoids

et al. 2016

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Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detail.

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Section: Chemistry and Classificationsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…Water-soluble analogs of limonin (1); and deoxylimonin (10) endowed with analgesic and anti-inflammatory properties [45].…”

mentioning

confidence: 99%

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The Chemistry and Pharmacology of Citrus Limonoids

et al. 2016

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Chemical Constituents from Citrus changshan‐huyou and Their Anti‐Inflammatory Activities

Hu¹,

Liu

et al. 2020

Chemistry & Biodiversity

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Limonin induces apoptosis of HL‐60 cells by inhibiting NQO1 activity

Chen

Liang

et al. 2021

Food Science & Nutrition

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Limonin is an important bioactive substance in citrus fruits, especially in seeds, which has great potential in cancer prevention and treatment. In order to explore the anticancer activity based on interaction between limonin and NQO1, Human promyelocytic leukemia cells (HL‐60) were studied in vitro. We found that limonin could inhibit proliferation and promote apoptosis of HL‐60 cells, and the effect was positively correlated with its dosage. Western blot results showed that limonin could activate the endogenous apoptosis pathway mediated by mitochondria via up‐regulating pro‐apoptotic proteins (Bax, cytochrome c, Caspase3, and Caspase9) and down‐regulating anti‐apoptotic proteins (Bcl‐2), thus inhibiting the proliferation of HL‐60 cells and promoting apoptosis, which further proved the anticancer activity of limonin from the molecular mechanism. At the same time, limonin down‐regulated the expression of NQO1, indicating that limonin may indirectly act on the apoptosis pathway by regulating the expression activity of antioxidant enzymes in vivo, thus exerting its inhibitory effect on tumor cells, which provides an idea for the molecular mechanism that natural products can indirectly exert their anticancer effect by regulating the activity of antioxidant enzymes.

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Synthesis and pharmacological evaluation of novel limonin derivatives as anti-inflammatory and analgesic agents with high water solubility

Cited by 39 publications

References 19 publications

The Chemistry and Pharmacology of Citrus Limonoids

The Chemistry and Pharmacology of Citrus Limonoids

Chemical Constituents from Citrus changshan‐huyou and Their Anti‐Inflammatory Activities

Limonin induces apoptosis of HL‐60 cells by inhibiting NQO1 activity

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