David G I Kingston

Virginia Tech | VT · Department of Chemistry

Adenodolichos paniculatus Hua & Hutch (Fabaceae) is a plant whose roots are traditionally employed for the treatment of non-communicable diseases such as diabetes and cancer. The powdered root bark of Adenodolichos paniculatus were extracted with dichloromethane followed by 70% methanol to afford dichloromethane (DCM) and hydromethanolic (HME) extr...

Phytochemical investigation of the methanol extract of the fruit rind of Myristica malabarica led to the isolation of eight known compounds that were identified as malabaricones A‐D, promalabaricones B and C, 1‐(2,6‐dihydroxyphenyl) tetradecane‐1‐one, and ericanone by comparison with literature spectroscopic data. The structures of malabaricones A‐...

Natural products have made a crucial and unique contribution to human health, and this is especially true in the case of malaria, where the natural products quinine and artemisinin and their derivatives and analogues, have saved millions of lives. The need for new drugs to treat malaria is still urgent, since the most dangerous malaria parasite, Pl...

Eight phloroglucinols from Garcinia dauphinensis were recently reported to have good to moderate antiplasmodial and anticancer activities, consistent with other phloroglucinol derivatives isolated from natural sources. Chiroptical properties were previously calculated and compared to experimental data for compound 2 as a means to deduce its absolut...

The author describes his 60-year career in studying the chemistry of natural products, which includes structural, synthetic, and biosynthetic studies of natural products ranging from insect pigments, antibiotics, and fecal mutagens to taxol and other anticancer natural products as well as antimalarial natural products. One of the compounds discusse...

Chromatographic separation of the acetone extracts from the twigs and barks of Artocarpus lakoocha led to the isolation of the one new flavanone, lakoochanone (1), together with eleven known compounds (2–12). Lakoochanone (1) and moracin C (4) exhibited weak antiplasmodial activity against Plasmodium falciparum Dd2 with IC50 values of 36.7 and 33.9...

Vitex rotundifolia is an important medicinal plant frequently employed in traditional medicines for the treatment of various ailments. Although this plant species has been under exploration for its constituents by various research groups including our own group, no reports were found regarding the antimalarial potential of this plant or of its puri...

An extract of Galtonia regalis from the Natural Products Discovery Institute showed moderate antiplasmodial activity, with an IC50 value less than 1.25 μg/mL. The two known cholestane glycosides 1 and 2 and the five new cholestane glycosides galtonosides A-E (3-7) were isolated after bioassay-directed fractionation. The structures of the new compou...

Alphitonia excelsa (Rhamnaceae) and Arcanglesia flava (Menispermaceae) are utilized by locals in Samar island for medicinal purposes. Extracts from twigs of A. excelsa exhibited antiproliferative activity against the A2780 human ovarian cancer cell line, while a stem extract of A. flava had potent activity in an antimalarial screen against the drug...

In our continuing search for novel natural products with antiplasmodial activity, an extract of Aniba citrifolia was found to have good activity, with an IC50 value less than 1.25 μg/mL. After bioassay-directed fractionation, the known indolizinium alkaloid anibamine (1) and the new indolizinium alkaloid anibamine B (2) were isolated as the major b...

Six known compounds, namely two halisulfates 1 and 2 and four epidioxy sterols 3–6 , were isolated from the marine sponge Coscinoderma sp. The structures of these compounds were confirmed by nuclear magnetic resonance ( ¹ H and ¹³ C NMR) spectroscopy, and their antiplasmodial activities were determined against the chloroquine-resistant Dd2 strain o...

Correction for ‘The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research’ by James B. McAlpine et al. , Nat. Prod. Rep. , 2018, DOI: 10.1039/c7np00064b.

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in c...

Garcinia dauphinensis is a previously uninvestigated endemic plant species of Madagascar. The new phloroglucinols dauphinols A–F and 3′-methylhyperjovoinol B (1–7) and six known phloroglucinols (8–13) together with tocotrienol 14 and the three triterpenoids 15–17 were isolated from an ethanolic extract of G. dauphinensis roots using various chromat...

Garcinia dauphinensis is a previously uninvestigated endemic plant species of Madagascar. The new phloroglucinols dauphinols A-F and 3'-methylhyperjovoinol B (1-7) and six known phloroglucinols (8-13) together with tocotrienol 14 and the three triterpenoids 15-17 were isolated from an ethanolic extract of G. dauphinensis roots using various chromat...

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in c...

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in c...

Bioassay-guided fractionation of an extract of Carpha glomerata (Cyperaceae) led to the isolation of seven compounds. Compounds 1 (carphorin A), 3 (carphorin C), 4 (carphorin D), and 5 (carphabene) are new compounds, and compound 2 (8-(3″-hydroxyisoamyl)-naringenin) was isolated for the first time as a natural product. All structures were elucidate...

Covering: up to 2018 With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets....

This work reports the isolation of the three known compounds, smenotronic acid ( 1 ), ilimaquinone ( 2 ), and pelorol ( 3 ), from the 85% methanol (MeOH)-soluble fraction of the sponge Hyrtios erectus . The structures of the isolated compounds were determined with the help of modern spectroscopic techniques, and the resulting compounds were then su...

An extract of Petradoria pumila from the Natural Products Discovery Institute was found to have moderate antiplasmodial activity, with an IC50 value between 5 and 10 μg/mL. The four new diterpenoids petradoriolides A–D (1–4), the new benzotropolone petradoriolone (5), and the two known lignans 6 and 7 were isolated after bioassay-directed fractiona...

Background: The advantages of nanomedicines include preferential delivery of the payload directly to tumor tissues. CYT-21625 is the novel, first-in-class gold nanomedicine designed to target tumor vasculature and cancer cells by specifically delivering recombinant human tumor necrosis factor alpha (rhTNF) and a paclitaxel prodrug. Methods: We a...

The structures of the α-pyrones cryptorigidifoliols E (5) and K (11) have been reassigned as 5C and 11C.

Doxorubicin is an effective and widely used cancer chemotherapeutic agent, but its application is greatly compromised by its cumulative dose-dependent side effect of cardiotoxicity. A gold nanoparticle-based drug delivery system has been designed to overcome this limitation. Five novel thiolated doxorubicin analogs were synthesized and their biolog...

A bioassay-guided fractionation and chemical investigation of Amaryllis belladonna Steud. bulbs resulted in the isolation and identification of the new crinane alkaloid 1,4-dihydroxy-3-methoxy powellan (1), along with the 3 known crinane alkaloids 2-4 and the two lycorane alkaloids 5-6. The structures were elucidated by interpretation of combined H...

Nine new compounds containing either a chromane or chromene ring moiety were isolated from the monotypic plant Koeberlinia spinosa. Compounds 1-4 are chromanes with all possible E and Z isomers of the isoprenoid side chain, with compound 5 a methylated derivative of 1. Compounds 6 and 7 were assigned as diastereomeric cyclized derivatives of 2 and...

An extract of a Malleastrum sp. (Meliaceae) collected in Madagascar by the Madagascar International Cooperative Biodiversity Group was found to have antimalarial activity, with an IC50 value between 2.5 and 5 μg/mL. After purification by liquid-liquid partition, chromatography on a Diaion open column, C-18 SPE and C-18 reverse phase HPLC, the new b...

Bioassay-guided fractionation of a methanol extract of Magnolia grandiflora against Plasmodium falciparum yielded two new (1 and 2) and six known (3 - 8) bioactive compounds. The structures of the new compounds were assigned by mass spectrometric and 1D and 2D NMR data. Known compounds were identified by comparison of (1) H NMR and MS data with lit...

Antiplasmodial bioassay guided fractionation of a Madagascar collection of Crinum firmifolium led to the isolation of seven compounds. Five of the seven compounds were determined to be 2-alkylquinolin-4(1H)-ones with varying side chains. Compounds 1 and 4 were determined to be known compounds with reported antiplasmodial activities, while 5 was bel...

Bioassay screening of plant extracts can identify unique lead compounds for drug development, but the “hit rate” from random screening is very low. Targeted screening of medicinal plants has been repeatedly reported to increase the percentage of samples displaying bioactivity. Contrarily, Maranz (2012) suggested that African antimalarial plants wer...

A dichloromethane extract of Trichospira verticillata from the Natural Products Discovery Institute was discovered to have good antiplasmodial activity (IC 50 ∼5 μg/mL). After purification by liquid−liquid partition and C 18 reversed-phase HPLC, four new germacranolide-type sesquiterpenoid lactones named trichospirolides A−D (1−4) were isolated. Th...

Inspired by the discovery of the antimalarial drug artemisinin from a traditional Chinese medicine (TCM), a natural product library of 44 lindenane-type sesquiterpenoids was assessed for activities against the Dd2 chloroquine-resistant strain of the malaria parasite Plasmodium falciparum. These compounds were mainly isolated from plants of the Chlo...

The synthesis of a series of thiolated paclitaxel analogs is described as part of a novel nanomedicine program aimed at developing formulations of paclitaxel that bind to gold nanoparticles for tumor targeted drug delivery. Evaluation of the analogs led to the selection of analog 5 as the basis for the new nanomedicine CYT-21625, comprised of 27 nm...

Melicope madagascariensis (Rutaceae) is an endemic plant species of Madagascar that was first classified as a member of the genus Euodia J. R. & G. Forst (Rutaceae) under the scientific name Euodia madagascariensis Baker. Based on morphological characteristics, Thomas Gordon Hartley taxonomically revised E. madagascariensis Baker to be M. madagasca...

Antimalarial bioassay-guided fractionation of the swamp lily Crinum erubescens led to the isolation of four compounds with potent antiplasmodial activity. Compounds 1 and 2 were determined from their spectroscopic data to be the known pesticidal compound cripowellin A and the known pesticidal and antiproliferative compound cripowellin B. 1D and 2D-...

Bioassay guided fractionation of the MeOH extract of the plant Gutierrezia sarothrae (Asteraceae) using an assay for antiplasmodial activity against the drug resistant Dd2 strain of Plasmodium falciparum led to the isolation of the two new diterpenes 3 alpha-angeloyloxy-15-hydroxylabda-7,13-dien-16,15-olid-18-oic acid (1) and 3 alpha-angeloyloxy-15...

The phloroglucinol mallotojaponin C (1) from Mallotus oppositifolius, which was previously shown by us to have both antiplasmodial and cytocidal activities against the malaria parasite Plasmodium falciparum, was synthesized in three steps from 2',4',6'-trihydroxyacetophenone, and various derivatives were synthesized in an attempt to improve the bio...

Bioassay guided fractionation of a MeOH extract of the stem bark of Syncarpia glomulifera (Myrtaceae) led to the isolation of the two new phloroglucinol derivatives (±)-rhodomyrtosone F (1) and (±)-calliviminone C (2), the three known triterpenes, betulinic acid (3), ursolic acid-3-acetate (4), and ursolic acid (5), and 1-(2,4,6-trihydroxyphenyl)-1...

Bioassay-guided fractionation of EtOH extracts obtained from the roots and wood of the Madagascan plant Leptaulus citroides Baill. (Cardiopteridaceae) led to the isolation of ethyl esters of three new triterpenoid saponins (1–3) and the known sesquiterpenoid cinnamosmolide (4). The structures of 1–3 were elucidated by extensive 1D and 2D NMR experi...

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In continuation of our ongoing search for bioactive compounds from microbial extracts, we performed antiproliferative and/or antimalarial assays on extracts of 806 microbial species isolated from Madagascan marine organisms, on 1317 species isolated from Madagascan soil samples and on a Streptomyces species (S.4) from a marine sponge collected from...

Antiproliferative bioassay-guided fractionation of the ethanolic extract of the endemic Madagascan plant Metaporana sericosepala led to the first natural product isolation of a butenolide diterpene which was synthesized during an anti-inflammatory study in 1988. The structure of the compound was elucidated as 3-homofarnesyl-4-hydroxybutenolide (1)...

An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (-)-kolavenol (4), and the known labdane diterpene 3-o...

The anticancer drug Taxol® (paclitaxel, 1) and its semisynthetic analogs docetaxel (2) and cabazitaxel (3) are some of the most effective weapons in the arsenal of drugs for the treatment of breast cancer, ovarian cancer, and various other cancers. The story of how the chemical compound taxol, discovered by Monroe Wall and Mansukh Wani as the major...

Malaria is a neglected tropical disease that has a disproportionate effect in poor and underdeveloped countries. As part of our ongoing search for new antimalarial compounds, an extract of the Swamp Lily Crinum erubescens was selected due to its potent antimalarial activity. Bioassay guided fractionation yielded four potent antimalarial compounds....

In a search for antimalarial natural products from plants in collaboration with the Natural Products Discovery Institute we investigated an antiplasmodial extract from Carapa guianensis (Meliaceae). This extract gave a DCM fraction with activity against the chloroquine-resistant Dd2 strain of P. falciparum with an IC50 value about 4 µg/mL. The four...

A CH2Cl2 extract of Trichospiras verticillata from the Natural Products Discovery Institute was found to have good antimalarial activity, with an IC50 value of 5 µg/mL. After purification by liquid-liquid partition, chromatography on Sephadex LH-20, and C-18 reverse phase HPLC, the four new sesquiterpenes 1 – 4 were isolated. The structures of the...

The two new lignans 3α-O-(β-d-glucopyranosyl)desoxypodophyllotoxin (1) and 4-O-(β-d-glucopyranosyl)dehydropodophyllotoxin (2) were isolated from Cleistanthus boivinianus, together with the known lignans deoxypicropodophyllotoxin (3), (±)-β-apopicropodophyllin (4), (-)-desoxypodophyllotoxin (5), (-)-yatein (6), and β-peltatin-5-O-β-d-glucopyranoside...

Antimalarial bioassay-guided fractionation of an EtOH extract of the root wood of Cryptocarya rigidifolia (Lauraceae) led to the isolation of the five new 5,6-dihydro-α-pyrones cryptorigidifoliols A-E (1-5) and the six bicyclic tetrahydro-α-pyrone derivatives cryptorigidifoliols F-K (6-11). The structure elucidations of all compounds were made on t...

Bioassay-guided fractionation of an EtOH extract of the roots of the plant Apoplanesia paniculata (Fabaceae) led to the isolation of the three known compounds amorphaquinone (1), pendulone (2), and melilotocarpan C (3), and the two new pterocarpans 4 and 5. Compounds 1 and 2 exhibited good antiplasmodial activity with IC50 values of 5.7 ± 1.5 and 7...

As part of the International Cooperative Biodiversity Group (ICBG) program, in a search for antiproliferative compounds, an ethanol extract of Polyscias duplicata was investigated due to its antiproliferative activity against the A2780 human ovarian cell cancer line (IC50 6 µg/mL). Seven known oleanane glycosides, 3β-[(α-l-arabinopyranosyl)oxy]-16α...

Bioassay-guided fractionation using the human colorectal adenocarcinoma (HT-29) cell line of the methanol extract of dried roots of Podocarpus falcatus led to the isolation of two new type C nagilactones, 16-hydroxynagilactone F (1) and 2β,16-dihydroxynagilactone F (2), and the new totarane-type bisditerpenoid 7β-hydroxymacrophyllic acid (4), along...

Natural compound schweinfurthins are of considerable interest for novel therapy development because of their selective anti-proliferative activity against human cancer cells. We previously reported the isolation of highly active schweinfurthins E-H, and in the present study, mechanisms of the potent and selective anti-proliferation were investigate...

Bioassay-directed fractionation of an antiproliferative ethanol extract of the roots of Ocotea macrocarpa (Lauraceae) afforded the new butanolide macrocarpolide A (1), and the two new secobutanolides macrocarpolides B (2) and C (3), together with the known butanolides linderanolide B (4), and isolinderanolide (5). The structure elucidation of all c...

Ten new neolignans including the 6'-oxo-8.1'-lignans cymosalignans A (1a), B (2), and C (3), an 8.O.6'-neolignan (4a), ococymosin (5a), didymochlaenone C (6a), and the bicyclo[3.2.1]octanoids 7-10 were isolated along with the known compounds 3,4,5,3',5'-pentamethoxy-1'-allyl-8.O.4'-neolignan, 3,4,5,3'-tetramethoxy-1'-allyl-8.O.4'-neolignan, didymoc...

Clinically, surgical isolation and local perfusion of intractable tumor bearing limbs with a vascular disrupting agent (VDA) and a chemotherapy is highly effective. CYT-20000 is a gold nanoparticle-based drug that delivers TNF (a VDA) and an inactive paclitaxel prodrug to any solid tumor, without the need for surgery. The nanotherapy is manufacture...

Bioassay-directed fractionation of an antiproliferative ethanol extract of the leaves and twigs of Piptocoma antillana (Asteraceae) afforded two new goyazensolide-type sesquiterpene lactones named 5-O-methyl-5-epiisogoyazensolide (1) and 15-O-methylgoyazensolide (2), together with the known compounds 1-oxo-3,10-epoxy-8-(2-methylacr1 0-epoxy-8-(2-me...

Paclitaxel (PTX), introduced into the clinic in 1991, has revealed itself as an effective antimicrotubule drug for treatment of a range of otherwise intractable cancers. Along with docetaxel (DTX) and in combination with other agents such as cisplatin, it has proven to be a first-line therapy. Unfortunately, PTX and DTX carry severe liabilities suc...

Four novel doxorubicin derivatives have been designed and synthesized. Comparable bioactivities to doxorubicin or even higher were observed against A2780 human ovarian cancer cell. By conjugating to the surface of gold nanoparticles modified with poly(ethylene glycol) (PEG) and TNFα, four new drug delivery systems have been established. From compar...

Bioassay-directed fractionation of an ethanol extract of the leaves and twigs of the antiproliferative plant Piptocoma antillana (Asparagaceae) afforded two new goyazensolide-type sesquiterpene lactones named piptoantilnolide A (1) and piptoantilnolide B (2), together with the known compounds 1-oxo-3,10-epoxy-8-metacriloxy-15-acetoxygermacra-2,4,11...

As part of our project in discovering bioactive natural products from plants, we identified two weakly cytotoxic compounds from Nidorella resedifolia (Asteraceae). Bioassay guided fractionation of the crude methanol extract led to isolation of two unusual sesquiterpene xylosides (1-2). The structures of 1 and 2 were elucidated as known compounds. T...

Covering: through January 2014 Zampanolide is a marine natural macrolide and a recent addition to the family of microtubule-stabilizing cytotoxic agents. Zampanolide exhibits unique effects on tubulin assembly and is more potent than paclitaxel against several multi-drug resistant cancer cell lines. A high-resolution crystal structure of αβ-tubulin...

The new triterpene turranoic acid (1) and the new N-containing nor-triterpene turraenine (2), along with triptocallic acid B (3) and esculentoic acid (4) were isolated from leaves of a Turraea sp. Compounds 1–3 showed weak to moderate in vitro antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum strain FCM29. Compound 1 a...

The epothilones, including epothilones B and D, are macrocyclic lactones, which have potent cytotoxicities and promote the polymerization of tubulin to mictotubules by binding to and stabilizing the tubulin polymer. They have a very similar mechanism of action to paclitaxel (Taxol®). The determination of the microtubule-binding conformation of the...

Four diastereoisomers, aphadilactones A-D (1-4) possessing an unprecedented carbon skeleton, were isolated from a Meliaceae plant Aphanamixis grandifolia. Their challenging structures and absolute configurations were determined by a combination of spectroscopic data, chemical degradation, fragment synthesis, experimental CD and ECD calculation. Aph...

Thioloated taxane derivatives are linked to colloidal metal particles such as gold nanoparticles for use as antitumor agents. The antitumor agents may be targeted to tumors.

Antiproliferative bioassay-guided fractionation of the ethanol extract of the stems of Anisocycla grandidieri led to the isolation of the known alkaloids stebisimine (1), (+)-1,2-dehydrotelobine (2), (+)-2'-norcocsuline (3) and puetogaline B (4). Herein, we report the full NMR assignments of all compounds and the X-ray crystallography of single cry...

In a continuing collaboration in a search for new antiproliferative compounds in Madagascar as part of an International Cooperative Biodiversity Group (ICBG), an ethanol extract of Molinaea retusa Radlk. (Sapindaceae) was investigated on the basis of its moderate antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 16 m...

Antimalarial bioassay-guided fractionation of an EtOH extract of the root wood of Cryptocarya rigidifolia (Lauraceae) led to the isolation of the five new 5,6-dihydro-α-pyrones cryptorigidifoliols A−E (1−5) and the six bicyclic tetrahydro-α-pyrone derivatives cryptorigidifoliols F−K (6−11). The structure elucidations of all compounds were made on t...

Investigation of the South African plant Urginea depressa Baker (Asparagaceae Juss.) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the six new homoisoflavonoids urgineanins A-F (1-6), the two known bufatrienolides 7 and 9, and the new bufatrienolides urginins B and C (8 and 10). Structures were el...

Dereplication of the antiproliferative ethyl acetate fraction of the Madagascan sponge Carteriospongia sp. led to the detection and isolation of the two known homoscalarane-type sesterterpenes 1 and 2. Investigation of a similar sponge containing closely related compounds afforded the four new antiproliferative homoscalarane sesterterpenes (3 and 5...

Paclitaxel (PTX) is a microtubule-stabilizing agent that is widely used in cancer chemotherapy. This structurally complex natural product acts by binding to beta-tubulin in assembled microtubules. The 2'-hydroxyl group in the flexible side chain of PTX is an absolute requirement for activity, but its precise role in the drug-receptor interaction ha...

Investigation of the endemic Madagascan plant Nematostylis anthophylla (Rubiaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the known triterpene saponin randianin (1), and the two new bioactive triterpene saponins 2″-O-acetylrandianin (2) and 6″-O-acetylrandianin (3). The structures of the tw...