Novel Strategies for the Discovery of Plant-Derived Anticancer Agents

Kinghorn, A. Douglas; Farnsworth, Norman R.; Soejarto, Djaja D.; Cordell, Geoffrey A.; Swanson, Steven M.; Pezzuto, John M.; Wani, Mansukh C.; Wall, Monroe E.; Oberlies, Nicholas H.; Kroll, David J.; Kramer, Robert A.; Rose, William C.; Vite, Gregory D.; Fairchild, Craig R.; Peterson, Russell W.; Wild, Robert A.

doi:10.1080/1388020039051744

Cited by 138 publications

(92 citation statements)

References 51 publications

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“…The 1 H NMR and HMQC NMR spectra obtained for 4 in pyridine-d 5 exhibited a pair of trans-coupled methine doublets at δ H 6.39 and 6.52 (H-12 and H-11, J = 16.4 Hz), corresponding to an asymmetrically substituted olefinic bond, and these 1 H NMR signals correlated in the HMQC NMR spectrum with 13 C NMR resonances at δ C 156.1 and 119.9 (C-11 and C-12, respectively). Analysis of the HMBC and HMQC NMR spectra confirmed that the connectivity and relative configuration of 4 were consistent with those of 1-3.…”

Section: Resultsmentioning

confidence: 97%

“…The IR spectrum indicated the presence of hydroxyl and α,β-unsaturated carbonyl resonances [3426 (br) and 1743 cm −1 ]. The 1 H, 13 C, and DEPT135 NMR spectra for 3 suggested that this isolate is based on a clerodane diterpene skeleton, similar to 1. Comparison of the 13 13 C correlations in the HMBC NMR spectrum of 3 were observed from H-12 to C-11, C-14, and C-16, and from H-16 to C-13 and C-14, thus confirming the structure of the side chain as being composed of an α, β-unsaturated butyrolactone with a two-carbon linker attached at the β-position.…”

Section: Resultsmentioning

confidence: 99%

“…Comparison of the 13 C NMR and DEPT135 NMR spectra for 5 indicated the presence of 20 carbons, including three methyls, seven methylenes, five methines, and five quaternary carbons. Visual inspection of the 1 H, DEPT135, and 13 C NMR spectra suggested a close homology between 5 and 1-4. HMBC NMR correlations for 5 were observed from H-14 to C-15 and C-16, from H-16 to C-13 and C-14, and from H-11 to C-9, C-12, and C-13, establishing the side chain structure as being the same as that of 3.…”

Section: Resultsmentioning

confidence: 99%

“…Additional HMBC correlations from H-18 to C-5, C-3, and C-4, from H-17 to C-7 and C-9, from H-19 to C-3, C-4, C-5, and C-10, and from H-20 to C-8, C-9, C-10, C-11, and C-12 (4J C-H ) helped to determine the structure of the decalin ring moiety. The assignment of C-1, C-2, and C-6 was complicated by the nearly overlapping 13 C NMR signals for C-1 and C-19 and for C-2, C-6, and C-8. The 1 H-13 C assignments for these signals are thus based on interpretation of the DEPT135, HMBC, and HMQC NMR spectra, and comparison with published values for 3β, 16ξ-dihydroxycleroda-4(18), 13-dien-15,16-olide.…”

Section: Resultsmentioning

confidence: 99%

“…Comparison of the 13 C NMR and DEPT135 NMR spectra for 1 indicated the presence of four methyl groups, five methylenes, three aliphatic methines, two olefinic methines, one methine with a chemical shift typical of a hemiacetal (δ c 98.4), and five quaternary carbons. The 1 H NMR spectrum for 1 contained signals for four downfield methines and four methyl groups, as well as a number of signals attributable to methylene protons.…”

Section: Resultsmentioning

confidence: 99%

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Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida^,1

Jones

Lobo-Echeverri

et al. 2007

J. Nat. Prod.

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Bioassay-guided fractionation of the combined fruits, leaves, and twigs (fruiting branches) of Callicarpa americana, collected from a plot in a forested area in southern Florida, led to the isolation of six new clerodane diterpenes (1-6) and eight known compounds. The structures of 1-6 [12(S), 16ξ-dihydroxycleroda-3,13-dien-15,16-olide (1), 12(S)-hydroxy-16ξ-methoxycleroda-3,13-dien-15,16-olide (2), 12(S)-hydroxycleroda-3,13-dien-15,16-olide (3), 16 ξ-hydroxycleroda-3,11 (E),13-trien-15,16-olide (4), 3β,12(S)-dihydroxycleroda-4(18),13-dien-15,16-olide (5), and 12(S)-hydroxycleroda-3,13-dien-16,15-olide (6)] were elucidated by interpretation of spectroscopic data and chemical methods. The absolute configuration at C-12 in 1 and 3 was ascertained using the Mosher ester technique. The cytotoxicity of all isolates was tested against a panel of human cancer cell lines, and compounds 1, 4, and 6, and the known compounds genkwanin, 16ξ-hydroxycleroda-3,13-dien-15,16-olide, and2-formyl-16ξ-hydroxy-3-A-norcleroda-2,13-dien-15,16-olide were active (ED 50 <5 μg/mL). However, 1 was found to be inactive against human cancer cells implanted in mice using a hollow-fiber tumor model. Callicarpa americana L. is a shrub native to the southeastern United States. 2 Although the genus has been considered traditionally as a member of the plant family Verbenaceae, molecular and micro-morphological observations have prompted contemporary taxonomic authorities to reclassify Callicarpa as a member of the family Lamiaceae. 3-5 Preparations of the bark of C. americana have been used to treat fever, 6 the leaves to treat dropsy, 7 and the roots to alleviate colic, 8 dysentery, 9 and skin cancer. 10 The roots and branches have been used in preparations intended to relieve malaria, rheumatism, and fever. 8 The leaf essential oils of C. americana have antialgal and mosquito-deterrent properties, and numerous essential oil components have been identified from the leaves of C. americana. [11][12] As part of an ongoing effort to discover novel anticancer agents from plants, 13 a chloroformsoluble extract of the combined fruits, leaves, and twigs of C. americana was investigated, using cytotoxicity against hormone-dependent prostate cancer cells (LNCaP) to guide the isolation of active constituents. This plant material was obtained from a forest plot in southern Florida using a plot-based collection method (briefly reviewed in ref. 13 ).⊥ Dedicated to the late Dr. Kenneth L. Rinehart of the University of Illinois at Urbana-Champaign for his pioneering work on bioactive natural products.*Author to whom correspondence should be addressed. Tel: (614) Results and DiscussionThe dried fruits, leaves, and twigs of Callicarpa americana L. were extracted with methanol and partitioned following a previously described protocol. 14 Based on the cytotoxic activity of the chloroform-soluble portion, bioassay-guided fractionation using a number of chromatographic techniques was carried out, guided by activity against LNCaP cells. This investigation re...

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida^,1

Jones

Lobo-Echeverri

et al. 2007

J. Nat. Prod.

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Plant and Marine Sources

Amedei

Niccolai

2014

Natural Products Analysis

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Chemical characterization and anti‐breast cancer effects of silver nanoparticles using Phoenix dactylifera seed ethanolic extract on 7,12‐Dimethylbenz[a] anthracene‐induced mammary gland carcinogenesis in Sprague Dawley male rats

Mohammadi

Zangeneh

et al. 2019

Applied Organom Chemis

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The aim of the recent research was to investigate the anti‐breast cancer effects of silver nanoparticles using Phoenix dactylifera seed ethanolic extract (AgNPs). After preparation of Phoenix dactylifera seed extract, GC/MS was performed to detect the compounds. The findings indicated that 9‐Octadecenoic acid (Z)‐ methyl ester (40.95%) and Dodecanoic acid methyl ester (20%) were the most frequent constituents found in P. dactylifera. These nanoparticles were spherical with a size range of 17‐19 nm and characterized using various analytical techniques including UV–Vis absorption spectroscopy to determine the presence of AgNPs in the solution. We studied functional groups of P. dactylifera extract in the reduction and capping process of AgNPs by FT‐IR, crystallinity and FCC planes by X‐ray diffraction (XRD) pattern and surface morphology, shapes, and size of AgNPs by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). DPPH free radical scavenging test was used to test the antioxidant properties of P. dactylifera and AgNPs, which revealed high antioxidant potential similar to butylated hydroxy toluene (BHT) as the positive control. The results of cytotoxicity analysis indicated that P. dactylifera and AgNPs were toxic for MCF‐7 cells. In vivo design, induction of breast cancer was done by 7,12‐Dimethylbenz[a] anthracene (DMBA) in 50 animals. After 10 days, the animals were randomly divided into six subgroups, including healthy control, untreated control, two groups receiving the P. dactylifera at 2 and 6 mg/kg and two groups receiving the AgNPs at 2 and 6 mg/kg concentrations. Both doses of P. dactylifera and AgNPs (especially AgNPs6) significantly (p ≤ 0.05) reduced the weight and volume of liver, mammary gland, kidney, spleen, ALP, AST, ALT, GGT, cholesterol, LDL, triglyceride, total and conjugated bilirubin, urea, creatinine, glucose, ferrous, ferritin, erythropoietin, GR, IL1, IL6, IL12, IL18, IFNY, and TNFα and increased HDL, total protein, albumin, WBC, lymphocyte, neutrophils, platelet, RBC, Hb, PCV, MCV, MCH, MCHC, SOD, CAT, GPx, IL4, IL5, IL10, IL13, and IFNα compared to the untreated group. Moreover, P. dactylifera and AgNPs (especially AgNPs6) significantly (p ≤ 0.05) treated breast cancer with reduction of organs free of metastasis compared to the untreated group. Seemingly, the AgNPs can be used for the treatment of breast cancer.

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Novel Strategies for the Discovery of Plant-Derived Anticancer Agents

Cited by 138 publications

References 51 publications

Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida^,1

Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida^,1

Plant and Marine Sources

Chemical characterization and anti‐breast cancer effects of silver nanoparticles using Phoenix dactylifera seed ethanolic extract on 7,12‐Dimethylbenz[a] anthracene‐induced mammary gland carcinogenesis in Sprague Dawley male rats

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Novel Strategies for the Discovery of Plant-Derived Anticancer Agents

Cited by 138 publications

References 51 publications

Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida,1

Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida,1

Plant and Marine Sources

Chemical characterization and anti‐breast cancer effects of silver nanoparticles using Phoenix dactylifera seed ethanolic extract on 7,12‐Dimethylbenz[a] anthracene‐induced mammary gland carcinogenesis in Sprague Dawley male rats

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Product

Resources

About

Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida^,1

Cytotoxic Constituents from the Fruiting Branches of Callicarpa americana Collected in Southern Florida^,1