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Discovery of Novel Drug Candidates from Plants
Kinghorn, A . Douglas,Seo, Eun Kyoung,Lee, Ik Soo 전남대학교 약품개발연구소 1996 약품개발연구지 Vol.4 No.1
This review provides a summary of some recent additions to the drugs that are derived from higher plants used clinically in North America and Europe, either in the form of pure entities or as extractives. Although the majority of the promising new drugs based on plant secondary metabolites mentioned are anticancer agents, as exemplified by vinorelbine and paclitaxel, derivatives of the antimalarial agent, artemisinin, and of the adenylate cyclase activator, forskolin, also offer considerable clinical promise. A major phytomedicine presently used in Europe is a standardized extract of Gingko biloba leaves, employed to treat cerebral insufficiency and other circulatory conditions. The senior author and his colleagues at the University of Illinois at Chicago have had a long-standing interest in the discovery of novel bioactive compounds from higher plants, of possible use as lead compounds for new drugs and food additives. Recent progress made in elucidating bioactive compounds from three research projects, directed towards the discovery of natural product anticancer substances, cancer chemopreventive agents, and noncariogenic sweeteners, respectively, will be briefly described.
Highly Sweet Compounds from North and South American Medicinal Plants
A. Douglas Kinghorn 한국생약학회 1991 생약학회지 Vol.22 No.1
Nearly 50 highly sweet substances have been isolated and structurally characterized from green plants, and such compounds comprise mainly various types of terpenoids, flavonoids, and proteins. Among the sweet substances that have been studied as constituents of North and South American medicinal plants are the sesquiterpene, hernandulcin, the triterpene glycosides, abrusosides A-D, the steroidal saponins, polypodosides A and B, and the dihydroflavonol, dihydroquercetin-3-acetate. In addition, safety studies have been performed on the potently sweet substance, stevioside, from the sweet herb of Paraguay (Stevia rebaudiana), a compound now produced on a commercial scale.
Ferdosi, Mohammad H,Kinghorn, Brian P,van der Werf, Julius HJ,Lee, Seung Hwan,Gondro, Cedric BioMed Central 2014 BMC bioinformatics Vol.15 No.-
<P><B>Background</B></P><P>Identification of recombination events and which chromosomal segments contributed to an individual is useful for a number of applications in genomic analyses including haplotyping, imputation, signatures of selection, and improved estimates of relationship and probability of identity by descent. Genotypic data on half-sib family groups are widely available in livestock genomics. This structure makes it possible to identify recombination events accurately even with only a few individuals and it lends itself well to a range of applications such as parentage assignment and pedigree verification.</P><P><B>Results</B></P><P>Here we present <I>hsphase</I>, an R package that exploits the genetic structure found in half-sib livestock data to identify and count recombination events, impute and phase un-genotyped sires and phase its offspring. The package also allows reconstruction of family groups (pedigree inference), identification of pedigree errors and parentage assignment. Additional functions in the package allow identification of genomic mapping errors, imputation of paternal high density genotypes from low density genotypes, evaluation of phasing results either from <I>hsphase</I> or from other phasing programs. Various diagnostic plotting functions permit rapid visual inspection of results and evaluation of datasets.</P><P><B>Conclusion</B></P><P>The <I>hsphase</I> package provides a suite of functions for analysis and visualization of genomic structures in half-sib family groups implemented in the widely used R programming environment. Low level functions were implemented in C++ and parallelized to improve performance. <I>hsphase</I> was primarily designed for use with high density SNP array data but it is fast enough to run directly on sequence data once they become more widely available. The package is available (GPL 3) from the Comprehensive R Archive Network (CRAN) or from http://www-personal.une.edu.au/~cgondro2/hsphase.htm.</P>
Highly Sweet Compounds of Plant Origin
Kim, Nam-Cheol,Kinghorn, A.-Douglas The Pharmaceutical Society of Korea 2002 Archives of Pharmacal Research Vol.25 No.6
The demand for new alternative "low calorie" sweeteners for dietetic and diabetic purposes has increased worldwide. Although the currently developed and commercially used highly sweet sucrose substitutes are mostly synthetic compounds, the search for such compounds from natural sources is continuing. As of mid-2002, over 100 plant-derived sweet compounds of 20 major structural types had been reported, and were isolated from more than 25 different families of green plants. Several of these highly sweet natural products are marketed as sweeteners or flavoring agents in some countries as pure compounds, compound mixtures, or refined extracts. These highly sweet natural substances are reviewed herein.
Ferdosi, Mohammad H,Kinghorn, Brian P,van der Werf, Julius H J,Gondro, Cedric BioMed Central 2014 Genetics, selection, evolution Vol.46 No.1
<P><B>Background</B></P><P>Identifying recombination events and the chromosomal segments that constitute a gamete is useful for a number of applications in genomic analyses. In livestock, genotypic data are commonly available for half-sib families. We propose a straightforward but computationally efficient method to use single nucleotide polymorphism marker genotypes on half-sibs to reconstruct the recombination and segregation events that occurred during meiosis in a sire to form the haplotypes observed in its offspring. These meiosis events determine a block structure in paternal haplotypes of the progeny and this can be used to phase the genotypes of individuals in single half-sib families, to impute haplotypes of the sire if they are not genotyped or to impute the paternal strand of the offspring’s sequence based on sequence data of the sire.</P><P><B>Methods</B></P><P>The hsphase algorithm exploits information from opposing homozygotes among half-sibs to identify recombination events, and the chromosomal regions from the paternal and maternal strands of the sire (blocks) that were inherited by its progeny. This information is then used to impute the sire’s genotype, which, in turn, is used to phase the half-sib family. Accuracy (defined as R<SUP>2</SUP>) and performance of this approach were evaluated by using simulated and real datasets. Phasing results for the half-sibs were benchmarked to other commonly used phasing programs – AlphaPhase, BEAGLE and PedPhase 3.</P><P><B>Results</B></P><P>Using a simulated dataset with 20 markers per cM, and for a half-sib family size of 4 and 40, the accuracy of block detection, was 0.58 and 0.96, respectively. The accuracy of inferring sire genotypes was 0.75 and 1.00 and the accuracy of phasing was around 0.97, respectively. hsphase was more robust to genotyping errors than PedPhase 3, AlphaPhase and BEAGLE. Computationally, hsphase was much faster than AlphaPhase and BEAGLE.</P><P><B>Conclusions</B></P><P>In half-sib families of size 8 and above, hsphase can accurately detect block structure of paternal haplotypes, impute genotypes of ungenotyped sires and reconstruct haplotypes in progeny. The method is much faster and more accurate than other widely used population-based phasing programs. A program implementing the method is freely available as an R package (hsphase).</P>
Plant-derived triterpenoid sweetness inhibitors
SuttisriIk, Rutt,Lee, Ik-Soo,Kinghorn, A . Douglas 전남대학교 약품개발연구소 1996 약품개발연구지 Vol.4 No.1
Considerable recent attention has been focused on naturally occurring compounds with taste-modifying activity, which are of potential use in both dietary sweetness management and in gaining a better understanding of the sweet taste sensation. This review summarizes information on the phytochemistry and biological activity of more than 40 triterpenoid sweetness inhibitors that have been isolated from the leaves of three medicinal plants, namely, Gymnema sylvestre R.Br. (Asclepiadacese), Ziziphus jujuba P. Miller (Rhamnaceae), and Hovenia dulcis Thunb. (Rhamnaceae).
Phenolic compounds from the leaves of Cornus controversa
Lee, Dongho,Kang, Shin-Jung,Lee, Seung-Ho,Ro, Jaiseup,Lee, Kyongsoon,Kinghorn, A.Douglas 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-
Two novel phenolie compounds from the leaves of Cornus controversa(Cornaceae) were characterized as (-)-2.3-digalloyl-4-(E)-caffeoyl-L-threonic acid and (-)-2-galloyl-4-(E)-caffeoyl-L-threonic acid, using spectroscopic methods. ⓒ 2000 Elsevier Science Ltd. All rights reserved.
5-(4-Hydroxyphenethenyl)-4,7-dime-thoxycoumarin, a New Constituent of Monotes engleri
Seo, Eun-Kyoung,Chai, Hee-Byung,Chagwedera, Tangai E.,Farnsworth, Norman R.,Cordell, Geoffrey A.,Pezzuto, John M.,Kinghorn, A. Douglas 梨花女子大學校 藥學硏究所 2000 藥學硏究論文集 Vol.- No.9
A new coumarin, 5-(4-hydroxyphenethenyl)-4,7-dimethoxycoumarin (1) was isolated from the combined ethyl acetate extracts of the root bark, root wood and stem bark of Monotes engleri, and found to be cytotoxic against two cell lines in a human tumor panel. Its structure was determined on the basis of spectroscopic methods.