Natural Products Discovery Institute

Doylestown, PA, United States

Natural Products Discovery Institute

Doylestown, PA, United States
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Yoo Y.J.,Ewha Womans University | Kim H.,University of Michigan | Park S.R.,Natural Products Discovery Institute | Yoon Y.J.,Ewha Womans University
Journal of Industrial Microbiology and Biotechnology | Year: 2016

Rapamycin is an immunosuppressive metabolite produced from several actinomycete species. Besides its immunosuppressive activity, rapamycin and its analogs have additional therapeutic potentials, including antifungal, antitumor, neuroprotective/neuroregenerative, and lifespan extension activities. The core structure of rapamycin is derived from (4R,5R)-4,5-dihydrocyclohex-1-ene-carboxylic acid that is extended by polyketide synthase. The resulting linear polyketide chain is cyclized by incorporating pipecolate and further decorated by post-PKS modification enzymes. Herein, we review the discovery and biological activities of rapamycin as well as its mechanism of action, mechanistic target, biosynthesis, and regulation. In addition, we introduce the many efforts directed at enhancing the production of rapamycin and generating diverse analogs and also explore future perspectives in rapamycin research. This review will also emphasize the remarkable pilot studies on the biosynthesis and production improvement of rapamycin by Dr. Demain, one of the world’s distinguished scientists in industrial microbiology and biotechnology. © 2016 Society for Industrial Microbiology and Biotechnology


Clement J.A.,Natural Products Discovery Institute | Clement J.A.,Western Carolina University | Willis T.J.,Western Carolina University
Natural Products Journal | Year: 2016

Eupatorium serotinum Michx. (late thoroughwort, Asteraceae) is a perennial herbaceous plant that is common to the eastern United States. The plant has diaphoretic effects, and has a folk remedy usage as a fever reducer. Relatively little is known about the chemistry of this plant. To better understand the chemistry of this plant and for the identification of taxonomic markers for the plant, we have isolated three sesquiterpenoids from Eupatorium serotinum. The compounds were identified by NMR and MS spectroscopic methods. © 2016 Bentham Science Publishers.


Dai Y.,Virginia Polytechnic Institute and State University | Harinantenaina L.,Virginia Polytechnic Institute and State University | Bowman J.D.,Virginia Polytechnic Institute and State University | Da Fonseca I.O.,Virginia Polytechnic Institute and State University | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2014

Bioassay-guided separation of the South African plant Kniphofia ensifolia for antiplasmodial activity led to the isolation of two new anthraquinones, named kniphofiones A and B (3 and 4), together with three known bioactive anthraquinone monomers (1, 2 and 5), and four known bisanthraquinones (6-9). The structures of the two new compounds were elucidated based on analyses of their 1D and 2D NMR spectra and mass spectrometric data. The dimeric compounds 6 and 7 displayed the strongest antiplasmodial activity among all the isolated compounds, with IC50 values of 0.4 ± 0.1 and 0.2 ± 0.1 μM, respectively. The two new compounds displayed modest activities, with IC50 values of 26 ± 4 and 9 ± 1 μM, respectively. Due to the synthetic accessibility of the new compounds and the increased activity shown by the dimeric compounds, a structure-activity relationship study was conducted. As a result, one analogue of kniphofione B (4), the caffeic acid derivative of aloe-emodin, was found to have the highest activity among all the aloe-emodin derivatives, with an IC50 value of 1.3 ± 0.2 μM. © 2013 Published by Elsevier Ltd. All rights reserved.


Clement J.A.,Natural Products Discovery Institute | Clement J.A.,Western Carolina University | Clement E.S.H.,Western Carolina University
Current Topics in Medicinal Chemistry | Year: 2014

The genus Aralia contains many plants used medicinally in Asia and the Americas. Although many members of this genus are used medicinally, the vast majority of this genus has not been explored chemically. The species of Aralia that have been explored chemically have yielded compounds of several classes, including triterpenoid saponins, sterols, diterpenoids, and acetylenic lipids. Many of the biologically active components found in genus Aralia have been evaluated for their potential as lead compounds for drug discovery. This review will explore the medicinal chemistry of compounds reported from genus Aralia, and future prospects for this genus will be considered. © 2014 Bentham Science Publishers.


Dai Y.,Virginia Polytechnic Institute and State University | Harinantenaina L.,Virginia Polytechnic Institute and State University | Brodie P.J.,Virginia Polytechnic Institute and State University | Goetz M.,Natural Products Discovery Institute | And 3 more authors.
Journal of Natural Products | Year: 2013

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 elucidated based on analysis of their 1D and 2D NMR spectra, electronic circular dichroism, and mass spectrometric data. Five of the six new homoisoflavonoids had good antiproliferative activity against the A2780 ovarian cancer, A2058 melanoma, and H522-T1 human non-small-cell lung cancer cells, and urgineanin A (1) had submicromolar activity against all three cell lines. The four bufatrienolides 7-10 had strong antiproliferative activity against the same cell line, with IC50 values of 24.1, 11.2, 111, and 40.6 nM, respectively. © 2013 The American Chemical Society and American Society of Pharmacognosy.


PubMed | Natural Products Discovery Institute and Virginia Polytechnic Institute and State University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2016

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-hexanone (6). Compound 1 exhibited strong antiplasmodial activity, while compounds 2-4 were moderately active and 5 and 6 were inactive in this assay. The structures of 1 and 2 were elucidated based on analyses of their mass spectrometric data, 1D and 2D NMR spectra, and comparison with related compounds.


PubMed | Natural Products Discovery Institute and Virginia Polytechnic Institute and State University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2016

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-NMR techniques were used to determine the identities of 3 and 4 as the new compounds cripowellin C and D. A fifth compound was identified as the known alkaloid hippadine, which was inactive against Plasmodium falciparum. The antiplasmodial IC


PubMed | Natural Products Discovery Institute and Virginia Polytechnic Institute and State University
Type: Journal Article | Journal: Planta medica | Year: 2015

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 5.71.5 and 7.00.8M, respectively. Compound 3 exhibited weak antiplasmodial activity (41.85.2M), while compounds 4 and 5 were inactive. Compound 6 was synthesized to confirm the structure of 5, and it showed enhanced antiplasmodial activity (15.81.4M) compared to its analogues 3-5.


PubMed | Natural Products Discovery Institute
Type: Journal Article | Journal: Journal of natural products | Year: 2015

Two new [(+)-cyrillins A (1) and B (2)] and four known barrigenol-like triterpenoids (3-6), along with betulinic acid and (+)-3-O-trans-feruloylbetulinic acid, were isolated from a sample-restricted CH2Cl2-soluble extract of the bark of Cyrilla racemiflora, collected in Dominica. The structures of the new compounds were elucidated by interpretation of their spectroscopic data, and the absolute configuration of the cyclic 1,2-diol unit of (+)-cyrillin A (1) was ascertained by analysis of the electronic circular dichroism (ECD) spectrum induced with [Mo2(OAc)4]. In the case of (+)-cyrillin B (2), which was found to contain a diangeloylated glucose residue, the structure proposed was supported by analysis of its MS(2) and MS(3) spectra. All compounds isolated were evaluated for their cytotoxicity against HT-29 human colon cancer cells, and the known compound, (+)-barringtogenol B (3), was found to be the most potent, exhibiting an IC50 value of 1.7 M. This compound also showed inhibitory activity toward the CCD-112CoN human normal colon cell line, with an IC50 value of 5.9 M, indicating a lack of cytotoxic selectivity.


PubMed | Natural Products Discovery Institute
Type: Journal Article | Journal: Current topics in medicinal chemistry | Year: 2015

The genus Aralia contains many plants used medicinally in Asia and the Americas. Although many members of this genus are used medicinally, the vast majority of this genus has not been explored chemically. The species of Aralia that have been explored chemically have yielded compounds of several classes, including triterpenoid saponins, sterols, diterpenoids, and acetylenic lipids. Many of the biologically active components found in genus Aralia have been evaluated for their potential as lead compounds for drug discovery. This review will explore the medicinal chemistry of compounds reported from genus Aralia, and future prospects for this genus will be considered.

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