Limonin Derivatives: Synthesis Using Methodology in Solution and Heterogeneous Medium and Evaluation of the Antimicrobial Activity

Tavares, Luciana C.; Fernandes, Tanize S.; Ilha, Vinícius; Neto, Alexandre Tiburski; Santos, Eveline W; Burrow, Robert A.; Duarte, Fábio A.; Flores, Érico M.M.; Silva, Ubiratan F.; Mostardeiro, Marco A.; Morel, Ademir F.

doi:10.5935/0103-5053.20150266

Cited by 4 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…m.p. 237 °C); [α] D 25 = -151 ( c 1.45 mg/mL, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ) δ: 7.54 (brs, 1H, -CN-O H ), 7.41 (s, 1H), 7.40 (s, 1H), 6.35 (s, 1H, H-22), 5.46 (s, 1H, H-17), 4.69 (d, J = 13.0 Hz, 1H, H-19), 4.36 (d, J = 13.0 Hz, 1H, H-19), 3.99 (s, 1H, H-1), 3.80 (s, 1H, H-15), 3.57 (d, J = 12.5 Hz, 1H), 2.98 (dd, J = 17.0, 3.5 Hz, 1H), 2.70 (d, J = 16.5 Hz, 1H), 2.42 (d, J = 11.0 Hz, 1H), 1.93–2.02 (m, 2H), 1.79–1.88 (m, 2H), 1.73–1.78 (m, 1H), 1.47–1.53 (m, 1H), 1.32 (s, 3H), 1.23 (s, 3H), 1.19 (s, 3H), 0.96 (s, 3H); HRMS (ESI): calcd for C 26 H 31 NO 8 Na ([M + Na] + ), 508.1942; found, 508.1944.…”

Section: Methodsmentioning

confidence: 99%

High Value-Added Application of Natural Products in Crop Protection: Semisynthesis and Acaricidal Activity of Limonoid-Type Derivatives and Investigation of Their Biocompatible O/W Nanoemulsions as Agronanopesticide Candidates

Huang

et al. 2021

J. Agric. Food Chem.

View full text Add to dashboard Cite

The increasingly serious resistance of Tetranychus cinnabarinus Boisduval to a wide range of insecticides/acaricides poses a major challenge to their control. The citrus processing industry generates a huge quantity of various wastes that contain many limonoids. To effectively utilize these byproducts and discover more potent green acaricidal molecules as sustainable alternatives for traditional resistant pesticides, various limonoid-type derivatives (halogenated/seven-membered lactam derivatives of obacunone and halogenated/oxime esters/oxime ethers/seven-membered lactam derivatives of limonin) were synthesized based on a diversity-oriented synthetic strategy. The key steric configurations of 10 derivatives were further confirmed by X-ray crystallography. Compound 9m, which displayed greater than 9.7-fold potent acaricidal activity of limonin, was of preeminence. In addition, some interesting structure−activity relationships were observed. Moreover, a biocompatible O/W nanoemulsion delivery system was used to prepare the limonin-based agronanoacaricide, which exhibited pronounced control efficiency against T. cinnabarinus Boisduval in the greenhouse. This systematic investigation will provide valuable information and guidance for future value-added applications of novel eco-friendly natural product-based nanopesticides.

show abstract

Section: Methodsmentioning

confidence: 99%

High Value-Added Application of Natural Products in Crop Protection: Semisynthesis and Acaricidal Activity of Limonoid-Type Derivatives and Investigation of Their Biocompatible O/W Nanoemulsions as Agronanopesticide Candidates

Huang

et al. 2021

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“…Natural limonin has an effective antibacterial effect, but the relevant dose of limonin derivative has stronger antibacterial activity than natural products. Modification in A-ring and at C-7 position of the limonin structure generated compounds that had strong antimicrobial activity [62].…”

Section: Pharmacologymentioning

confidence: 99%

Limonin: A Review of Its Pharmacology, Toxicity, and Pharmacokinetics

et al. 2019

View full text Add to dashboard Cite

Limonin is a natural tetracyclic triterpenoid compound, which widely exists in Euodia rutaecarpa (Juss.) Benth., Phellodendron chinense Schneid., and Coptis chinensis Franch. Its extensive pharmacological effects have attracted considerable attention in recent years. However, there is no systematic review focusing on the pharmacology, toxicity, and pharmacokinetics of limonin. Therefore, this review aimed to provide the latest information on the pharmacology, toxicity, and pharmacokinetics of limonin, exploring the therapeutic potential of this compound and looking for ways to improve efficacy and bioavailability. Limonin has a wide spectrum of pharmacological effects, including anti-cancer, anti-inflammatory and analgesic, anti-bacterial and anti-virus, anti-oxidation, liver protection properties. However, limonin has also been shown to lead to hepatotoxicity, renal toxicity, and genetic damage. Moreover, limonin also has complex impacts on hepatic metabolic enzyme. Pharmacokinetic studies have demonstrated that limonin has poor bioavailability, and the reduction, hydrolysis, and methylation are the main metabolic pathways of limonin. We also found that the position and group of the substituents of limonin are key in affecting pharmacological activity and bioavailability. However, some issues still exist, such as the mechanism of antioxidant activity of limonin not being clear. In addition, there are few studies on the toxicity mechanism of limonin, and the effects of limonin concentration on pharmacological effects and toxicity are not clear, and no researchers have reported any ways in which to reduce the toxicity of limonin. Therefore, future research directions include the mechanism of antioxidant activity of limonin, how the concentration of limonin affects pharmacological effects and toxicity, finding ways to reduce the toxicity of limonin, and structural modification of limonin—one of the key methods necessary to enhance pharmacological activity and bioavailability.

show abstract

“…Besides the diverse medicinal properties, they also displayed promising insecticidal and anti-tobacco mosaic virus (TMV) activities. Limonin ( 1 , Figure ), the most abundant limonoid from citrus, is the typical representative of limonoids. − On the other hand, works in our group have focused on the structural optimization of the representative limonoids such as toosendanin ( 1′ , Figure ), obacunone ( 2 , Figure ), and fraxinellone ( 2′ , Figure ) as pesticidal candidates. Some derivatives 1′a , 2a , and 2′a–e (Figure ) containing the ester moiety in proper positions exhibited more potent insecticidal activities than their corresponding precursors. − In addition, oximinoethers ( 1a , Figure ) and amides ( 1b , Figure ) of limonin at the C-7 position as anti-inflammatory and analgesic agents were reported, and some compounds showed much better activities than limonin ( 1 ). , To make full use of citrus industrial wastes in crop protection, a series of ester derivatives of limonin modified in the B ring as pesticidal agents, by using limonin as a lead compound, were prepared in this study (Figure ).…”

Section: Introductionmentioning

confidence: 99%

High Value-Added Use of Citrus Industrial Wastes in Agriculture: Semisynthesis and Anti-Tobacco Mosaic Virus/Insecticidal Activities of Ester Derivatives of Limonin Modified in the B Ring

Huang

Shan

et al. 2020

J. Agric. Food Chem.

View full text Add to dashboard Cite

Globally, the citrus industry produces various wastes, which contain a great deal of limonoids. In order for the sustainable development of the citrus industry, and considering the diverse bioactivities of limonoids, a series of ester derivatives were constructed by structural modification of limonin in the B ring. Furthermore, two seven-membered lactone derivatives of limonin and obacunone with a novel skeleton in the B ring were obtained by the Baeyer–Villiger oxidation rearrangement. The steric structures of six key compounds 3a, 3b, 4m, 4n, 6, and 7 were determined by X-ray crystallography. It demonstrated that the molar ratio of 3a (7α-isomer) and 3b (7β-isomer) depended on the mixed solvents in the reduction system. The anti-tobacco mosaic virus (TMV) activities under three different modes of action for most of the tested compounds were as the following sequence: inactivation effect > protection effect > curative effect. It was noteworthy that compound 4aa displayed the most potent anti-TMV/insect growth inhibitory activities, which indicated that the introduction of the phenylacryloyloxy group at the C-7β position of limonin could significantly improve its agricultural biological activities. This study will pave the way for future value-added application of citrus industrial wastes and provide strong evidence for the discovery of sustainable biopesticides based on limonoids.

show abstract

Limonin Derivatives: Synthesis Using Methodology in Solution and Heterogeneous Medium and Evaluation of the Antimicrobial Activity

Cited by 4 publications

References 0 publications

High Value-Added Application of Natural Products in Crop Protection: Semisynthesis and Acaricidal Activity of Limonoid-Type Derivatives and Investigation of Their Biocompatible O/W Nanoemulsions as Agronanopesticide Candidates

High Value-Added Application of Natural Products in Crop Protection: Semisynthesis and Acaricidal Activity of Limonoid-Type Derivatives and Investigation of Their Biocompatible O/W Nanoemulsions as Agronanopesticide Candidates

Limonin: A Review of Its Pharmacology, Toxicity, and Pharmacokinetics

High Value-Added Use of Citrus Industrial Wastes in Agriculture: Semisynthesis and Anti-Tobacco Mosaic Virus/Insecticidal Activities of Ester Derivatives of Limonin Modified in the B Ring

Contact Info

Product

Resources

About