Quinoline alkaloids and cytotoxic lignans from Haplophyllum tuberculatum

doi:10.1016/S0031-9422(00)82500-5

Phytochemistry

Volume 26, Issue 12, 1987, Pages 3339-3341

https://doi.org/10.1016/S0031-9422(00)82500-5 Get rights and content

Abstract

Three quinoline alkaloids and two lignan lactones were isolated from Haplophyllum tuberculatum. Physicochemical and spectral evidence established the structures of two of the alkaloids as a new quinoldione, 3-(1′,1′-dimethylallyl)-3-(3″,3″-dimethylallyl)-1,2,3,4-tetrahydro-2,4-quinoldione and the known 4-(3′,3′-dimethylallyloxy)-3-(3″,3″-dimethylallyl)-2(1H)-quinolone. The former was shown to undergo facile [3,3]-sigmatotropic transformation into the latter. The remaining compounds were identified as the known Polygamain, kusunokinin and 1-methyl-2-n-nonyl-4(1H)-quinolone.

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Lignans and stilbenes are two groups of related secondary metabolites widely distributed in the plant kingdom. Both lignans and stilbenes possess anticancer, antioxidant, antimicrobial, anti-inflammatory, and immunosuppressive activities. In the present chapter, we have reported the cytotoxicity of 13 lignans, 16 stilbenes, and 2 neolignans isolated from African medicinal plants on various human cancer cell lines. The most potent cytotoxic lignans were diphyllin (2), futokadsurin B (3), justicidins A (4) and B (5), kusunokinin (6), pycnanthulignenes A (10) and B (11), and tuberculatin (13). The best stilbenes include combretastatin A-1 (14), combretastatin B-1 (15), combretastatin B-3 (16), combretastatin B-4 (17), longistylins A (18) and (19), mundulea lactone (20), schweinfurthins A (23), B (24), E (25), F (26), and G (27), and vedelianin (29). The two reported cytotoxic neolignans were licarins A (30) and B (31). Amongst these compounds, those that can combat the multidrug resistance of cancer were identified as 3, 10, 11, and 20. Some of the active lignans and stilbenes displayed apoptotic cell death in cancer cells, mainly mediated by caspase activation, alteration of MMP, and enhanced ROS production in cancer cells. The above lignans, neolignans, and stilbenes deserve further in-depth studies to develop novel cytotoxic products to fight cancer.
Cytotoxicity and selectiveness of Brazilian Piper species towards oral carcinoma cells
2019, Biomedicine and Pharmacotherapy
Citation Excerpt :
Some signals between δ 2.00 and 3.00 ppm can be attributed to the diastereotopic hydrogens of the saturated carbons. The NMR spectrum of PCa-L-D showed two double duplets at δ 6.53 (J = 7.8, 1.7 Hz) and 6.24 (J = 7.3, 1.4 Hz) and four duplets at δ 6.66 (J = 7.9 Hz), 6.63 (J = 8.2 Hz), 6.56 (J = 1.6 Hz), and 6.39 (J = 1.7 Hz), representing aromatic hydrogens, and a multiplet at δ 5.86 and singlets between δ 3.80 and 3.78, representing to methylenedioxy and two methoxyl groups, respectively [24–26]. Moreover, the GC–MS analysis of PC-L-D identified the sesquiterpene octahydro-2,2,5a,9-tetramethyl-2H-3,9a-methano-1-benzoxepin (9) (6.0%), methyl 3-(3,4-dimethoxyphenyl)propanoate (10) (2.7%) and neophytadiene (11) (2.5%).
Oral squamous cell carcinoma (OSCC) is one of the ten most common types of cancer worldwide. Plants of the genusPiper are used in traditional medicine to treat cancer, and they have a vast diversity of phytochemicals with cytotoxic potential.
Purpose and Study Design: In this work, we analyzed the cytotoxic and selective potential of extracts and semipurified fractions of Piper mollicomum (PM), Piper truncatum (PT), Piper cernuum (PC), Piper arboreum (PA), and Piper cabralanum (PCa) using three different OSCC cell lines (SCC4, SCC9 and SCC25), and we measured their in vivo toxicities and conducted chemical analyses of their active fractions.
The dichloromethane fractions of the crude methanolic extracts of the leaves of PM(-L-D), PC(-L-D) and PCa(-L-D) exhibited notable IC₅₀ values of 94.2, 47.2 and 47.5 μg/mL, respectively, and all three of these extracts were more active than carboplatin (172.3 μg/mL). The most selective fraction was PC-L-D, which exhibited SI > 4.5; less than 5% hemolysis; and no significant alterations in in vivo acute toxicology. The major constituents in active fractions were lignans (PC-L-D and PCa-L-D) and chromenes (PM-L-D).
PC-L-D demonstrated great potential for further development as an anticancer drug and could be the key to developing more effective and less toxic therapies against oral cancer.
Pharmacological activities of the organic extracts and fatty acid composition of the petroleum ether extract from Haplophyllum tuberculatum leaves
2018, Journal of Ethnopharmacology
Citation Excerpt :
The lignan justicidin E was found to be an inhibitor of leukotriene biosynthesis by human leukocytes (IC50 = 70 nM) and a non-redox inhibitor of the 5-lipoxygenase activity (Thérien et al., 1993). H. tuberculatum is rich in lignans and alkaloids (Al-Shamma et al., 1979; Hamdi et al., 2018; Sheriha et al., 1987; Sheriha and Amer, 1984). These two classes showed anti-inflammatory activity (Prieto et al., 1996; Souto et al., 2011).
Haplophyllum tuberculatum is used in traditional medicine to treat many disorders including inflammation and pain. The aim of this study is to investigate the organic extracts from H. tuberculatum leaves against inflammation, gastric ulcer and pain. Materials and methods: Acute toxicity was studied in vivo to determine the toxic doses of the organic extracts. Anti-inflammatory activity was also evaluated in vivo using carrageenan-induced paw edema in Wistar rats. Gastroprotective activity was tested using the HCl/ethanol-induced gastric ulcer test in rats. Peripheral and central analgesic activities were assessed using the acetic acid-induced writhing test and the hot-plate method, respectively. The chemical composition of the fatty acids in the petroleum ether (PE) extract was determined with GC-MS.
At 25, 50 and 100 mg/kg PE extract was the most active against inflammation. Percentages inhibition 5 h after carrageenan-injection were 51.12; 86.71% and 96.92%, respectively. The same extract at 100 mg/kg showed good analgesic activities using the acetic acid-induced writhing test and the hot-plate method. The chloroform, ethyl acetate (EtOAc) and butanolic (n-BuOH) extracts exhibited strong anti-inflammatory, gastroprotective and analgesic activities at 100 mg/kg. The GC-FID analysis revealed that the PE extract was rich in γ-linolenic acid (45.50%) followed by palmitic acid (18.48%), linoleic acid (10.73%), erucic acid (4.72), stearic acid (3.96%) and oleic acid (2.57%).
The results of the present study support the traditional use of the leaves of H. tuberculatum and may possibly serve as prospective material for further development of safe new phytochemical anti-inflammatory, gastroprotective and/or analgesic agents.
Polyphenolic contents, antioxidant activities and UPLC–ESI–MS analysis of Haplophyllum tuberculatum A. Juss leaves extracts
2018, International Journal of Biological Macromolecules
Citation Excerpt :
Isorhamnetin and syringetin-3-glucoside are only identified in the EtOAc extract. Previous works showed that vanillic acid, caffeic acid, isorhamnetin, syringetin, β-fagarine, g-fagarine, justicidin B, justicidin A, kusunokinin, tubacetine are also identified in aerial part of H. tuberculatum [5,16,22,33,34]. Moreover, arabelline, majidine, dictamnine and qudsine were found in Haplophyllum species [20], but are detected now for the first time in the species H. tuberculatum.
The aim of this study is to determine the phytochemical profile, the total polyphenolic contents and the antioxidant activities of Haplophyllum tuberculatum leaves extracts. The most active extracts were analyzed by ultra-high performance liquid chromatography coupled to electrospray ionization mass spectrometry. Antioxidant activities were screened by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) test and measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and β-carotene bleaching inhibition assays. Phytochemical screening of the extracts revealed the presence of various secondary metabolites. The ethyl acetate extract was the richest extract in phenolics and flavonoids with 262 mg gallic acid equivalents/g and 99.1 mg quercetin equivalent/g of dry weight, respectively. The same extract showed an important scavenging effect on DPPH, ABTS and β-carotene/linoleic acid with IC₅₀ of 0.020 mg/mL, 0.029 mg/mL and 0.022 mg/mL, respectively. The correlations between the antioxidant capacities and the polyphenolic content were ranging between 0.889 and 0.256 and occasionally found to be significant. The UPLC–ESI–MS analysis showed the presence of polyphenolic and alkaloid compounds. Arabelline, majidine, dictamine and a qudsine derivative are found for the first time in H. tuberculatum. The results indicate that polyphenolic and alkaloid compounds may be major contributors to the antioxidant activity of these extracts.
Phytotoxic activities of essential oils and hydrosols of Haplophyllum tuberculatum
2017, Industrial Crops and Products
Citation Excerpt :
The chemical composition of the essential oils from this species collected from different regions has been studied and varied considerably across the regions of collection (Al-Rehaily et al., 2014; Al-Yousuf et al., 2005; Al-Burtamani et al., 2005). In addition, several classes of compounds such as alkaloids, lignans, coumarins and flavonoids have been isolated from the aerial parts of H. tuberculatum (Al-Shamma et al., 1979; Ulubelen and Öztürk, 2008; Sheriha et al., 1987). Hydrosols, also named hydrolates, distillate water and aromatic water are the by-products or co-products produced during water or steam distillation of plant material.
Phytotoxic properties of plants and their compounds against other plants or seeds are being increasingly reported. Moreover, essential oils may provide a new source of phytotoxic agents with possibly novel mechanisms of action. The aim of this study is to determine the chemical composition of the leaves, stems and leaves + stems essential oils by GC/MS and to assess their phytotoxic activities extracted from Haplophyllum tuberculatum A. Juss. (Forssk) as well as of the aromatic water obtained from these parts and of the roots. The phytotoxic activities of the essential oils and hydrosols were evaluated against Triticum aestivum L. and Raphanus sativus L. seeds. The GC–MS analysis revealed the presence of limonene, cis-p-menth-2-en-1-ol, trans-p-menth-2-en-1-ol, cis-piperitol, trans-piperitol, 1-octyl acetate, piperitone and isobornyl acetate as major compounds. Phytotoxic results showed that the assayed stems essential oils were active on the roots inhibition (IC₅₀ = 1.09 mg/mL) for wheat. Leaves + stems essential oils had a significant activity against the tested seeds with IC₅₀ ranged from 0.70 to 1.46 mg/mL for radical and epicotyls/coleoptiles percentage inhibition against T. aestivum L. and R. sativus L. While the hydrosols of leaves, stems and leaves + stems inhibited seeds germination at a higher concentration. The essential oils of this plants cannot be used as biologic herbicide with these cultivated plants.
Synthesis of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4-dihydro- 1H-quinolin-2-ones, as novel quinoline derivatives with antibacterial activity
2014, European Journal of Medicinal Chemistry
A novel series of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4-dihydro-1H-quinolin-2-ones was synthesized and tested as antimicrobials. The minimum inhibitory concentration (MIC) values of the most active heterocycles were slightly higher than those exhibited by levofloxacin, employed as comparator. Structural factors affecting the activity were explored along three diversification points, including the substituents of the aromatic rings of the 3-benzyl moieties, as well as the functionalization of both, the homocyclic ring of the heterocycle and the quinolonic nitrogen atom. 6-Chloro and 3,3-bis(4′-chlorobenzyl) derivatives showed the lower MIC values. Optimally substituted heterocycles were synthesized, which exhibited enhanced activity.

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Quinoline alkaloids and cytotoxic lignans from Haplophyllum tuberculatum

Abstract

Phytochemistry

Phytochemistry

Tetrahedron

Phytochemistry

Tetrahedron Letters

Phytochemistry

Phytochemistry

J. Med. Chem.

Z. Naturforsch