Antimycobacterial evaluation of Peruvian plants.
We present the results of an antimycobacterial screening of 270 Peruvian plant samples representing 216 species from 171 genera in 63 families. Dichloromethane extracts were tested at a concentration of 50 [micro]g/ml for inhibition of Mycobacterium tuberculosis in radiometric culture. Slightly more than half of the samples tested showed inhibition of M. tuberculosis at this concentration.
Key words: Antimycobacterial agents, plant extracts, Mycobacterium tuberculosis, Pharmacognosy, Angiosperms
Among adults, tuberculosis (TB) is now the worldwide leading cause of death. The etiologic agent responsible for this infectious disease, Mycobacterium tuberculosis, causes more than 25% of avoidable adult deaths in developing countries (Pio and Chaulet, 1998). Acquired drug resistance (Kuaban et al. 2000) and AIDS-related opportunistic TB infection (Ashley et al. 2000) exacerbate both the scope and scale of the current global TB epidemic (Newton et al. 2000). If current levels of TB control are not strengthened, estimates are that nearly one billion people will be infected with TB in the next 30 years (WHO, 2000).
The research presented here is a response to the clear and urgent need to find new anti-tubercular agents. Although a number of plant extracts have been shown to inhibit the growth of Mycobacteria in a variety of in vitro assay systems (Azarowicz et al. 1952; Cantrell et al. 1998; Fitzpatrick, 1954; Frisbey et al. 1954; Gottshall et al. 1949; Grange and Davey, 1990; Lucas et al. 1951; McChesney et al. 1985; Newton et al. 2000; Wang, 1950), none has so far resulted in the development of any new, clinically useful, antitubercular agents.
Our objective was to provide candidates for further antimycobacterial evaluation, with the ultimate goal of identifying preparations with potential efficacy in the treatment of TB infection. Toward this end, dichloromethane extracts of 216 Peruvian plant species were screened for antimycobacterial activity using the BACTEC 460 (Becton Dickinson Diagnostic Instrument Systems, Sparks MD) radiometric assay. Using these bioactivity data, extracts with strong inhibitory activity against M. tuberculosis will be prioritized for further analysis.
* Materials and Methods
Specimens of each plant were pressed and dried in the field following standard botanical procedures (Alexiades, 1996). For every plant reported here, there has been a voucher specimen deposited at the John G. Searle herbarium of the Field Museum of Natural History in Chicago, Illinois, U.S.A. Specimens were identified by one of the authors (JGG) and a number of specialists listed in the acknowledgements.
All plant materials that were used in this experiment were collected fresh, then air-dried in situ. Any sample that showed signs of mold or spoilage was discarded. A small amount of the dried plant material was milled to a coarse powder, and ten gram portions of the dried, milled plant material were weighed out and placed into individual 400 ml glass extraction flasks. 150 ml of dichloromethane was added to each flask, and the flasks were stoppered and placed in an unlighted fume hood for 48 hours. After 48 hours, the flasks were decanted and filtered through medium filter paper, then evaporated in vacuo, yielding crude dichloromethane extracts that were used to prepare DMSO stock solutions for the antimycobacterial analyses.
In vitro radiometric assays were performed using a BACTEC 460 (Becton Dickinson Diagnostic Instrument Systems, Sparks MD) detector. This semi-automated system monitors the growth of Mycobacterium tuberculosis in BACTEC 12B vials containing Middlebrook 7H 12 broth medium. The broth medium contains a [sup.14]C-labelled substrate that is utilized by the mycobacteria as it grows, with [sup.14]C[O.sub.2] being produced as a metabolic by-product. The amount of [sup.14]C[O.sub.2] detected reflects the rate and amount of growth occurring in the vial, and is expressed as a Growth Index (GI).
For this experiment, a susceptible strain (ATCC 27294) of M. tuberculosis was utilized. Crude dichloromethane extracts of plant material were reconstituted to a concentration of 1 mg per ml of 100% dimethylsulfoxide (DMSO), filtered, and injected into the Bactec 12B vials to give a final concentration of 50 ug of plant extract per one ml of broth culture. The final volume of DMSO per vial is 5%, which is sufficiently dilute so as not to affect the growth of the organism. To verify this, blank controls, containing the same volume of DMSO as the sample vials, were run with each experiment. Positive controls, containing the antimycobacterial drugs rifampin at a concentration of 2 [micro]g/ml, and ethambutol at a concentration of 7.5 [micro]g/ml, were included as well. All samples, blanks, and positive controls were run in duplicate. Following the introduction of the samples, a uniform suspension of M. tuberculosis was then introduced into each BACTEC 12B vial. The GI of the sample vials were compared with those of the control vials, and growth inhibitions calculated.
All extracts that inhibited the growth of M. tuberculosis by 50% or more are included in Table 1. Those extracts that had less than 50% inhibition of M. tuberculosis at 50 ug/ml are listed in Table 2. Several extracts with strong growth inhibition of M. tuberculosis were further analyzed to determine the minimum inhibitory concentration (MIC). Results of this experiment are listed in Table 3.
We have identified a number of plant extracts with substantial inhibitory effect, in vitro, on the growth of M. tuberculosis. This study represents the first phase of ongoing research to identify new agents that are safe and effective for the treatment of TB. Experiments are currently underway to further evaluate the antimyco-bacterial potential of several of the most active of these extracts.
Interestingly, only two of the six plant species for which MIC were determined (Table 3) had any previous phytochemical analysis. Neither the acetylenes isolated from the bark of Heisteria acuminata (Kraus et al. 1998) nor the isoquinoline alkaloid, steroid and lignans isolated from the stem bark of Zanthoxylum sprucei (Binutu et al. 2000) are reported to have any significant antimycobacterial activity. The triterpene lupeol, as well as the flavanone sesamin, both found in Z. sprucei, are reported to have strong in vitro activity against Mycobacterium tuberculosis (Gangadharam et al. 1953; Wachter et al. 1999), and the presence of these compounds may account for the antimycobacterial activity encountered in this species.
Two Senna species, Senna silvestris (Veil.) Irwin & Barneby var. silvestris and Senna obliqua (G. Don) Irwin & Barneby, proved to be some of the most active of the plant extracts screened in this investigation. In vitro antimycobacterial activity has not been reported previously in the genus Senna. Prior to this study, neither S. silvestris nor S. obliqua were investigated, either in terms of their biological activity or their phytochemical makeup, although one may assume that since quinoid compounds are such a notable constituent for other species in the genus (Hegnauer, 2001), they probably occur in S. obliqua and S. silvestris as well. Significant antimicrobial activities have been reported for this compound class, (Jaki et al. 2000; Kazmi et al. 1994; Rath et al. 1995; Schinazi et al. 1990; Tagahara et al. 1992), including antimycobacterial activity (Gangadharam, 1990; Kanokmedhakul, 2002).
Prioritization of leads for further investigation will be based on several general criteria, including: antimycobacterial activity, lack of phytochemical investigation, and access to sufficient material for further analysis. Based on the first criterion, all those extracts with greater than 90% inhibition of M. tuberculosis at 50 [micro]g/ml provide a pool of possible candidates for further investigation. Based on the second criterion, Zanthoxylum sprucei, because it contains previously-identified antimycobacterial compounds, will probably not be considered strongly for further investigation. Mechanisms for acquisition of sufficient plant materials for further analysis are being explored.
Various collection approaches and selection criteria have been used to prioritize plants for pharmaceutical investigation. The biodiversity-based approach (Soejarto, 1996) used in the collection of the plant samples in this experiment provided a number of strongly active leads, in this case about three percent of the total sampie, screening at crude extract concentrations of 50 [micro]g/ml. This hit-rate could undoubtedly have been increased if we had used higher concentrations of extract for the initial antimycobacterial evaluations. Several other large-scale antimycobacterial screening efforts have tested at concentrations of 100 [micro]g/ml, 1 mg/ml, or even 20 mg/ml (McChesney and Adams, 1985). We felt that the use of 50 [micro]g/ml for initial screening was appropriate, as it should identify the most potent agents and eliminate further testing for extracts with only minimal antimycobacterial activity.
In this experiment dichloromethane was chosen as an extraction solvent. This choice was made in the interest of saving time, both because the solvent has a relatively low boiling point and evaporation time is greatly reduced compared to a more polar solvent such as methanol or water, but also because it reduces the number of manipulations needed in the extraction process. The relative selectivity of this non-polar solvent allows the preclusion of a time-consuming step of partitioning between chloroform and water to remove polar components and other unwanted trivial compounds.
Plants from the Peruvian Amazon appear to be a particularly rich source of potentially novel antitubercular compounds. The combination of significant antimycobacterial activity encountered in extracts obtained from this region (Franzblau, 2001), along with the general lack of phytochemical investigation for many of these species, represents a unique collaborative research opportunity for Peruvian institutions and investigators, and provides further incentive for biodiversity conservation at local and regional levels.
Table 1. Plant extracts with greater than 50% inhibition of Mycobacterium tuberculosis at 50 [micro] g/ml. Family species plant part % inhibition Annonaceae Annona hypoglauca Mart. bark 51 Apocynaceae Aspidosperma parvifolium A. DC. root 52 Lacmellea peruviana (van Heurck & Muell. Arg.) Markgr. stem 50 Aristolochiaceae Aristolochia cauliflora Ule stem 81 Boraginaceae Cordia nodosa Lam. bark 80 Chrysobalanaceae Couepia ulei Pilger bark 80 Compositae Ambrosia peruviana Willd. leaf and flower 58 Ambrosia peruviana Willd stem 81 Egletes viscosa (L.) Lessing whole plant 54 Trichospira verticillata (L) Blake whole plant 56 Vernonia patens H.B.K. root 61 Zexmenia wedeloides Klatt whole plant 53 Connaraceae Connarus elsae Forero bark 71 Convolvulaceae Iseia luxurians (Moricand) O'Donell whole plant 70 Cyperaceae Scleria melaleuca Rchb. whole plant 67 ex Schtdl. & Cham. Dilleniaceae Tetracera parviflora (Rusby) Sleumer stem 75 Euphorbiaceae Chamaesyce hirta (L.) Millspaugh whole plant 55 Flacourtiaceae Banara nitida Spruce ex Benth. stem 56 Laetia corymbosa Spruce ex Benth. stem 51 Guttiferae Clusia rosea L. stem 63 Lauraceae Nectandra hihua (R. & P.) Rowher bark 98 Leguminosae Andira sp. leaf 67 cf. Cynometra bauhiniifolia Benth. bark 88 Dalbergia sp. root 63 Erythrina fusca Loureiro bark 63 Erythrina fusca Loureiro root 54 Indigofera truxillensis H.B.K. whole plant 53 Senna silvestris (Vell.) I.& B. var. silvestris bark 94 Senna obliqua (G.Don) I.& B. stem and fruit 90 Loranthaceae Phoradendron obtusissimum (Miq.) Eichl. stem 69 Phthrusa aff. stelis (L.) Kuijt leaf 86 Malphigiaceae Tetrapterys discolor (G Meyer) DC. stem 89 Meliaceae Guaria guidonia (L.) Sleumer leaf 74 Menispermaceae Abuta grandifolia (Mart.) Sandwith leaf 57 Myrsinaceae Stylogine cauliflora (Miq. & C. Mart.) Mez stem 68 Myrtaceae Myrcia dichasialis McVaugh bark 50 Olacaceae Heisteria acuminata (Humb.& Bonpl.) Engler stem 92 Piperaceae Peperomia alata R.& P. whole plant 60 Piper enlongatum M. Vahl stem 84 Piper sp. stem 67 Piper sp. stem and leaf 93 Rubiaceae Chomelia malaneoides Muell. Arg. stem 55 Rudgea cf. loretensis Standl. stem 59 Sommera sabiceoides Schum. stem 96 Rutaceae Dictyoloma peruvianum Planch. leaf 56 Dictyoloma peruvianum Planch. stem 72 Monnieria trifolia L. whole plant 62 Zanthoxylum sprucei Engler bark 95 Sapindaceae Cupania sp. bark 67 Paullinia hystrix Radlk. stem 67 Solanaceae Cyphomandra oblongifolia Bohs stem 54 Zingiberaceae Dimerocostus sp. leaf 56 Table 2. Plant extracts with less than 50% inhibition of Mycobacterium tuberculosis at 50 [micro]g/ml. Acanthaceae: Sanchezia sprucei Lindau (stem) Amaranthaceae: Chamissoa altissima (Jacq.) H.B.K. var. altissima (stem), Iresine diffusa H.B.K. (stem) Anacardiaceae: Spondias mombin L. (bark) Annonaceae: Duguetia odorata (Diels) J.F Macbr. (bark), Rollinia cuspidata C. Mart. (bark) Apocynaceae: Aspidosperma parvifolium A. DC. (bark; leaf), Forsteronia amblybasis Blake (stem), Rauvolfia pentaphylla Huber ex Ducke (stem), Rhabdadenia macrostoma (Benth.) Muell. Arg. (whole plant) Tabernaemontana heterophylla Vahl. (bark), Tabernaemontana siphilitica (L. f.) Leeuw. (root), Tabernaemontana sananho R&P (stem) Araceae: Dracontium loretense Krause (corm) Bignoniaceae: Anaemopegma chrysoleucum (H.B.K.) Sandwith (stem), Anaemopegma paraense Bureau & Schumann (stem), Arrabidaea cinnamomea (A. DC.) Sandw. (stem), Callichlamys latifolia (Richard) Schumann (stem), Crescentia amazonica Ducke (stem), Cydista lilacina A. Gentry (stem), Lundia corymbifera (Vahl) Sandw. (stem), Martinella obovata (H.B.K.) Bureau & Schum. (stem), Tanacium nocternum (Barb. Rodr.) Bureau & Schum. (stem) Bombacaceae: Pachira insignis (Swartz) Swartz ex Savigny (stem) Boraginaceae: Cordia collococca L. (bark), Heliotropium indicum L. (whole plant), Tournefortia setacea Killip (stem) Capparidaceae: Capparis sp. (stem), Crateva tapia L. (bark) Cecropiaceae: Coussapoa sp. (stem) Chrysobalanaceae: Couepia ulei Pilger (stem) Combretaceae: Buchenavia grandis Ducke (stem), Combretum assimile Eichl. (stem), Combretum laxum Jacquin (stem), Thiloa paraguarensis Eichler (stem) Compositae: Vernonia canescens H. B. K. (stem & leaf), Vernonia patens H.B.K. (stem) Connaraceae: Rourea amazonica (Baker) Radlk. (stem) Cucurbitaceae: Cayaponia sp. (stem & root), Gurania spinulosa (Poepp. & Endl.) Cogn. (stem), Luffa operculata (L.) Cogniaux (whole plant) Cyperaceae: Diplasia karatifolia L. C. Rich. (leaf; root) Elaeocarpaceae: Sloanea sp. (stem) Euphorbiaceae: Alchornea brevistyla Pax & Hoffmann (bark), Croton cuneatus Klotzsch (bark), Croton sp. (root), Euphorbia sp. (whole plant), Euphorbia heterophylla L. (whole plant), Mabea nitida Spruce ex Benth. (bark), Margaritaria nobilis L.f. (bark), Phyllanthus sp. (stem), Sapium marmierii Huber (stem), Flacourtiaceae: Banara arguta Briquet (bark), Casearia sp. (bark; stem), Laetia sp. (stem), Lindackeria maynensis Poepp. (stem) Gnetaceae: Gnetum nodiflorum Brongniart (stem) Guttiferae: Garcinia madruno (Kunth) Hammel (bark), Vismia amazonica Ewan (stem), Vismia macrophylla Kunth (stem) Hippocrataceae: Hippocratea volubilis L. (stem) Lamiaceae: Leonurus sibiricus L. (root; stem & leaf) Lauraceae: Cinnamomum triplinerve (R. & P.) Kostermans (stem), Nectandra sp. (bark; root), Nectandra cuneato-cordata Mez (stem), Ocotea cernua s.l. (Nees) Mez (bark; root), Pleurotherium parviflorum Ducke (bark) Leguminosae: Acacia polyphylla DC. (bark), Acacia sp. (stem), Acacia farnesiana L. (stem), Albizia subimidiata (Splitb.) Barneby & Grimes (bark), Andira inermis (W.Wright) H.B.K. ex DC. (bark), Andira sp. (fruit), Bauhinia sp. (bark; root; stem), Browneopsis ucayalina Huber (root), Calliandra angustifolia Spruce ex Benth. (stem), Cassia sp. (stem), Crotalaria retusa L. (leaf & stem; root), Dalbergia sp. (stem); Dioclea sp. (stem), Entada polyphylla DC. (stem), Inga sp. (bark, fruit), Lonchocarpus densiflorus Benth. (stem), Lonchocarpus sp. (bark; stem), Machaerium aristulatum (Spruce ex Benth.) Ducke (stem), Machaerium sp. (stem), Mimosa myriadenia (Benth.) var. punctulata (Benth.) Barneby (stem), Samanea tubulosa (Benth.) Barneby & Grimes (fruit, stem), Senna silvestris (Vell.) I.& B. var. silvestris (stem), Swartzia simplex (Sw.) Spreng var. ochnacea (DC.) Cowan (bark), Zygia c.f. coccinea (G. Don) Rico, s. 1. (bark), Zygia vasquezii Rico (stem) Loganiaceae: Strychnos jobertiana Baillon (fruit, stem), Strychnos tarapotensis Sprague & Sandw. (stem) Loranthaceae: Phoradendron obtusissimum (Miq.) Eichl. (whole plant), Phoradendron piperoides (HBK) Trel. (whole plant), Phoradendron sp. (leaf; stem), Phthrusa aft. Stelis (L.) Kuijt (stem) Malphigiaceae: Bunchosia argentea (Jacq.) DC. (stem), Byrsonima japurensis Adr. Juss. (bark) Stigmaphyllon florosum C. Anderson (stem) Malvaceae: Hibiscus furcellatus Desrousseaux (stem), Sida acuta Burman f. (whole plant), Sida glomerata Cavanilles (whole plant), Wissadula excelsior (Cavanilles) C. Presl. (stem) Melastomataceae: Miconia c.f. splendens (Swartz) Griseb. (stem), Tococa sp. (stem) Meliaceae: Guaria guidonia (L.) Sleumer (bark), Trichilia rubra C. DC. (bark), Trichilia singularis C.DC. (stem) Menispermaceae: Abuta grandifolia (Mart.) Sandwith (root; stem), Chondrodendron tomentosum R. & P. (stem), Curarea sp. (stem), Orthomene schomburgkii (Miers) Krukoff & Barneby (root; stem), Monimiaceae: Siparuna poepigii (Tulasne) A. DC. (stem) Moraceae: Batocarpus amazonicus (Ducke) Fosberg (bark), Ficus maxima Miller (bark), Trophis racemosa (L) Urban subsp, meridionalis (Bureau) W.Burger (stem) Myrtaceae: Campomanesia lineatifolia R. & P. (stem), Eugenia egensis DC. (stem), Eugenia patens Poiret (stem), Psidium acutangulum DC. (bark; stem) Nyctaginaceae: Neea divaricata Poepp. & Endl. (stem) Ochnaceae: Ouratea pendula Engler (stem) Palmae: Bactris brongniartii Mart. (bark), Oenocarpus batahua C. Mart. (pedicel) Passifloraceae: Passiflora auriculata H.B.K. (leaf; stem), Passiflora coccinea Aubl. (root; stem), Passiflora sp. (stem) Piperaceae: Piper sp. (root) Polygonaceae: Coccoloba acuminata H. B. K. (root; stem), Coccoloba densifrons C. Mart. ex Meissner (stem), Triplaris americana L. (bark) Rhamnaceae: Gouania lupuloides (L.) Urb. (stem) Rubiaceae: Calycophyllum spruceanum (Benth.) Hook.f. ex Schumann (bark), Guettarda sp. (stem), Palicourea croceoides Ham. (stem), Psychotria marginata Sw. (stem), Psychotria mathewsii Standl. (stem) Rutaceae: Zanthoxylum sprucei Engler (leaf) Sapindaceae: Cupania cinera Poepp. (bark; root), Cupania sp. (fruit; leaf; root), Talisia sp. (bark; stem) Sapotaceae: Pouteria reticulata (Engler) Eyma (bark), Sarcaulus brasiliensis (A. DC.) Eyma (bark) Simaroubaceae: Picramnea latifolia Tulasne (leaf, root) Smilacaceae: Smilaxfebrifuga Kunth, (leaf, root; stem) Solanaceae: Brunfelsia grandiflora D. Don (leaf, root), Cestrum reflexum Sendtner (stem), Solanum grandiflorum R. & P. (root; stem), Solanum sessile R. & P. (stem) Sterculiaceae: Guazuma crinita Mart. (bark), Guazuma ulmifolia Lam. (bark, stem), Tiliaceae: Apeiba tibourbou Aubl. (bark) Trigoniaceae: Trigonia sericea H.B.K. (stem) Ulmaceae: Celtis iguanaea (Jacquin) Sargent (stem) Verbenaceae: Aegiphila chrysantha Hayek (stem), Lippia alba (Mill.) N.E. Br. (whole plant), Lippia betulaefolia H.B.K. (whole plant), Priva lappulaceae (L.) Persoon (aerial parts; root), Vitex cymosa Bert. ex Sprengel (bark) Violaceae: Corynostylis arborea (L.) S.F.Blake (stem), Leonia racemosa Mart. (bark), Leonia glycicarpa R. & P. (stem) Zingiberaceae: Costus sp. (rhizome), Renealmia sp. (rhizome & leaf) Table 3. Minimum Inhibitory Concentrations (MIC) of selected plant extracts. Family species part MIC Leguminosae Senna silvestris (Vell.) bark <6.25 [micro]g/ml I. & B. var. silvestris Rubiaceae Sommera sabiceoides stem <6.25 [micro]g/ml Schum. Lauraceae Nectandra hihua bark 10 [micro]g/ml (R. & P.) Rowher Leguminosae Senna obliqua fruit & 10 [micro]g/ml (G. Don) I. & B. stem Olacaceae Heisteria accuminata stem 10 [micro]g/ml (Numb. & Bonpl.) Engler Rutaceae Zanthoxylum bark 15 [micro]g/ml sprucei Engler
We would like to thank the Instituto Nacional de Medicina Tradicional (INMETRA), Ministry of Health, Lima, Peru, for their generous assistance, without which this project would not have been possible. Thanks to the staff at the herbarium of the Field Museum, Chicago, especially Robin Foster, Mike Dillon, Jack Regalado, Tyana Wachter and Chris Niezgoda. Thanks as well to the following botanists who assisted in the taxonomic determinations: Rupert Barneby, Charlotte Taylor, Mike Nee, Dieter Wasshausen, Tom Croat, Paul Maas, Lucia Lohmann, Ricardo Callejas, Blanca Leon, Job Kuijt, Terry Pennington, Nancy Hensold, Henk van der Werff, Gerrit Davidse, and Bruce Holst.
Alexiades MN (1996) Standard techniques for collecting and preparing herbarium specimens, in Alexiades, M, ed. Selected guidelines for ethnobotanical research. Bronx, New York: New York Botanical Garden
Ashley EA, Johnson MA, Lipman MC (2000) Human immunodeficiency virus and respiratory infection. Current Opinion in Pulmonary Medicine 6: 240-245
Azarowicz E, Hughes J, Perkins C (1952) Antibiotics in plants of Southern California active against Mycobacterium tuberculosis and Aspergillus niger. Antibiotics and Chemotherapy 2: 532-536
Binutu OA, Cabieses F, Cordell GA (2000) Constituents of Zanthoxylum sprucei. Pharmaceutical Biology 38: 210-213
Cantrell CL, Nunez IS, Castaneda-Acosta J, Foroozesh M, Fronczek FR, Fischer NH, Franzblau SC (1998) Antimycobacterial activities of Dehydrocostus lactone and its oxidation products. J Nat Prod 61: 1181-1186
Frisbey A, Roberts J, Jennings J, Gottshall R, Lucas E (1953) The occurrence of antibacterial substances in seed plants with special reference to Mycobacterium tuberculosis (Third Report). Michigan State College of Agriculture and Applied Science Quarterly Bulletin 35: 392-404
Fitzpatrick F (1954) Plant substances active against Mycobacterium tuberculosis. Antibiotics and Chemotherapy 4: 528-532
Franzblau Scott (2001) Personal communication
Gangadharam PRJ (1990) In vivo treatment of mycobacterial infections with 6-cyclo-octylamino-5,8-quinoline quinone (gangarnicin). U.S. Patent 4963565 A 19901016
Gangadharam PRJ, Natarajan S, Wadhawani TK, Giri KV, Narayvanmurty NL, Iyer BH (1953) Antitubercular activity of Sesamin. Journal of the Indian Institute of Science 35A: 69-76
Gottshall R, Lucas E, Lickfeldt A, Roberts J (1949) The occurrence of antibacterial substances active against Mycobacterium tuberculosis. Journal of Clinical Investigation 28: 920-923
Grange J, Davey R (1990) Detection of antituberculous activity in plant extracts. Journal of Applied Bacteriology 6: 587-591
Hegnauer R (2001) Chemotaxonomie der Pflanzen, Band X1b-2 Leguminosae, Teil 3. Basel: Birkhauser Verlag
Jaki B, Heilmann J, Sticher O (2000) New antibacterial metabolites from the cyanobacterium Nostoc commune (EAWAG 122b). Journal of Natural Products 63: 1283-1285
Kanokmedhakul S, Kanokmedhakul K, Phonkerd N, Soytong K, Kongsaeree P, Suksamrarn A (2002) Antimycobacterial Anthraquinone-Chromanone Compound and Diketopiperazine Alkaloid from the Fungus Chaetomium globosum KMITL-N0802. Planta Medica 68: 824-836
Kazmi MH, Malik A, Hameed S, Akhtar N, Alli SN (1994) An anthraquinone derivative from Cassia italica. Phytochemistry 36: 761-763
Kraus CM, Neszmalyi A, Holly S, Wiedmann B, Nenninger A, Torssell KBG, Bohlin L, Wagner H (1998) New acetylenes from the bark of Heisteria acuminata. Journal of Natural Products 61: 422-427
Kuaban C, Bercion R, Jifon G, Cunin P, Blackett KN (2000) Acquired anti-tuberculosis drug resistance in Yaounde, Cameroon. International Journal of Tuberculosis and Lung Disease 4: 427-432
Lucas E, Lickfeldt R, Gottshall R, Jennings J (1951) The occurrence of antibacterial substances in seed plants with special reference to Mycobacterium tuberculosis. Bulletin of the Torrey Boanical Club 78: 310-321
McChesney JD, Adams RP (1985) Co-evaluaton of plant extracts as petrochemical substitutes and for biologically active compounds. Economic Botany 39: 74-86
Newton SM, Lau C, Wright CW (2000) A review of natural antimycobacterial products. Phytotherapy Research 14: 303-322
Pio A, Chaulet P (1998) Tuberculosis Handbook. Geneva, World Health Organization
Rath G, Ndonzao M, Hostettmann K (1995) Antifungal anthraquinones from Morinda lucida. International Journal of Pharmacognosy 33: 107-114
Schinazi RF, Chu CK, Babu JR, Oswald BJ, Saalmaan V, Cannon DL, Eriksson BFH, Nasr M (1990) Anthraquinones, a new class of antiviral agents against Human Immunodeficiency Virus. Antiviral Research 13: 265-272
Soejarto DD (1996) Biodiversity prospecting and benefit-sharing: perspectives from the field. Journal of Ethnopharmacology 51: 1-16
Tagahara K, Koyama J, Ogura T, Konoshima T, Kozuka M, Tokuda H, Nishino H, Iwashima A (1992) Electronic properties and inhibitory effects of Epstein-Barr virus activation of mono- and di-substituted anthraquinones. Chemistry Express 7: 557-560
Wachter GA, Valcis S, Flagg ML, Franzblau SG, Montenegro G, Suarez E, Timmermann BN (1999) Antitubercular activity of pentacyclic triterpenoids from plants of Argentina and Chile. Phytomedicine 6: 341-345
Wang F (1950) In vitro antibacterial activity of some common Chinese herbs on Mycobacterium tuberculosis. Chin Med J 68: 169-172
WHO (2000) Tuberculosis. Fact Sheet No. 104, Revised April, 2000. Geneva: World Health Organization.
J. G. Graham, Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, The University of Illinois at Chicago, 833 South Wood Street, Chicago Illinois, 60612
Tel.: ++1-312-996-7254; Fax: ++1-312-413-5894; e-mail: firstname.lastname@example.org
J. G. Graham (1), S. L. Pendland (2), J. L. Prause (2), L. H. Danzinger (2), J. Schunke Vigo (3), F. Cabieses (3), and N. R. Farnsworth (1)
(1) Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, The University of Illinois at Chicago, Chicago Illinois
(2) Microbiology Research Laboratory, Department of Pharmacy Practice, College of Pharmacy, The University of Illinois at Chicago, Chicago Illinois
(3) National Institute of Traditional Medicine (INMETRA), Peruvian Ministry of Health, Lima, Peru
|Printer friendly Cite/link Email Feedback|
|Author:||Graham, J.G.; Pendland, S.L.; Prause, J.L.; Danzinger, L.H.; Vigo, J. Schunke; Cabieses, F.; Farnswo|
|Publication:||Phytomedicine: International Journal of Phytotherapy & Phytopharmacology|
|Date:||Jul 1, 2003|
|Previous Article:||In vitro evaluation of Bacopa monniera on anti-Helicobacter pylori activity and accumulation of prostaglandins.|
|Next Article:||Inhibitory activity of xanthine oxidase and superoxide-scavenging activity in some taxa of the lichen family Graphidaceae.|