Plants: A Source for New Antimycobacterial Drugs

Abstract

Tuberculosis, also called TB, is currently a major health hazard due to multidrug-resistant forms of bacilli. Global efforts are underway to eradicate TB using new drugs with new modes of action, higher activity, and fewer side effects in combination with vaccines. For this reason, unexplored new sources and previously explored sources were examined and around 353 antimycobacterial compounds (Nat Prod Rep 2007; 24: 278–297) [7] have been previously reported. To develop drugs from these new sources, additional work is required for preclinical and clinical results. Since ancient times, different plant part extracts have been used as traditional medicines against diseases including tuberculosis. This knowledge may be useful in developing future powerful drugs. Plant natural products are again becoming important in this regard. In this review, we report 127 antimycobacterial compounds and their antimycobacterial activities. Of these, 27 compounds had a minimum inhibitory concentration of < 10 µg/mL. In some cases, the mechanism of activity has been determined. We hope that some of these compounds may eventually develop into effective new drugs against tuberculosis.

Key words

alkaloids - flavonoids - chalcones - coumarins - lignans - phenols - terpenes - chromones - alkane - alkene - plants - Mycobacterium tuberculosis

• References

• 1 Jain A, Dixit P. Multidrug resistant to extensively drug resistant tuberculosis: what is next?. J Biosci 2008; 33: 605-616
• 2 McChesney JD, Venkataraman SK, Henri JT. Plant natural products: back to the future or into extinction?. Phytochemistry 2007; 68: 2015-2022
• 3 Jayaseelan KV, Moreno P, Truszkowski A, Ertl P, Steinbeck C. Natural product-likeness score revisited: an open-source, open-data implementation. BMC Bioinformatics 2012; 13: 106
• 4 Ortholand JY, Ganesan A. Natural products and combinatorial chemistry: back to the future. Curr Opin Chem Biol 2004; 8: 271-280
• 5 Amarendra V, Santhosh RS, Dhevendaran K. Sponges: a reservoir for microorganism derived bioactive metabolites. In: Kim S-K, editor Marine microbiology: bioactive compounds and biotechnological applications. Weinheim: Wiley-VCH; 2013: 417-452
• 6 García A, Bocanegra-García V, Palma-Nicolás JP, Rivera G. Recent advances in antitubercular natural products. Eur J Med Chem 2012; 49: 1-23
• 7 Copp BR, Pearce AN. Natural product growth inhibitors of Mycobacterium tuberculosis . Nat Prod Rep 2007; 24: 278-297
• 8 Ignacimuthu S, Shanmugam N. Antimycobacterial activity of two natural alkaloids, vasicine acetate and 2-acetyl benzylamine, isolated from Indian shrub Adhatoda vasica Ness. leaves. J Biosci 2010; 35: 565-570
• 9 Jha DK, Panda L, Lavanya P, Ramaiah S, Anbarasu A. Detection and confirmation of alkaloids in leaves of Justicia adhatoda and bioinformatics approach to elicit its anti-tuberculosis activity. Appl Biochem Biotechnol 2012; 168: 980-990
• 10 Jin J, Zhang J, Guo N, Feng H, Li L, Liang J, Sun K, Wu X, Wang X, Liu M, Deng X, Yu L. The plant alkaloid piperine as a potential inhibitor of ethidium bromide efflux in Mycobacterium smegmatis . J Med Microbiol 2011; 60: 223-229
• 11 Pallant CA, Cromarty AD, Steenkamp V. Effect of an alkaloidal fraction of Tabernaemontana elegans (Stapf.) on selected micro-organisms. J Ethnopharmacol 2012; 140: 398-404
• 12 Sureram S, Senadeera SPD, Hongmanee P, Mahidol C, Ruchirawat S, Kittakoop P. Antimycobacterial activity of bisbenzylisoquinoline alkaloids from Tiliacora triandra against multidrug-resistant isolates of Mycobacterium tuberculosis . Bioorg Med Chem Lett 2012; 22: 2902-2905
• 13 Panseeta P, Lomchoey K, Prabpai S, Kongsaeree P, Suksamrarn A, Ruchirawat S, Suksamrarn S. Antiplasmodial and antimycobacterial cyclopeptide alkaloids from the root of Ziziphus mauritiana . Phytochemistry 2011; 72: 905-915
• 14 Lin YM, Zhou Y, Flavin MT, Zhou LM, Nie W, Chen FC. Chalcones and flavonoids as anti-tuberculosis agents. Bioorg Med Chem 2002; 10: 2795-2802
• 15 Habbu PV, Mahadevan KM, Shastry RA, Manjunatha H. Antimicrobial activity of flavanoid sulphates and other fractions of Argyreia speciosa (Burm.f) Boj. Indian J Exp Biol 2009; 47: 121-128
• 16 Coelho RG, Honda NK, Vieira MC, Brum RL, Pavan FR, Leite CQF, Cardoso CAL. Chemical composition and antioxidant and antimycobacterial activities of Bromelia balansae (Bromeliaceae). J Med Food 2010; 13: 1277-1280
• 17 Fushiya S, Kishi Y, Hattori K, Batkhuu J, Takano F, Singab AN, Okuyama T. Flavonoids from Cleome droserifolia suppress NO production in activated macrophages in vitro . Planta Med 1999; 65: 404-407
• 18 Chou TH, Chen JJ, Peng CF, Cheng MJ, Chen IS. New flavanones from the leaves of Cryptocarya chinensis and their antituberculosis activity. Chem Biodivers 2011; 8: 2015-2024
• 19 Kuete V, Ngameni B, Mbaveng AT, Ngadjui B, Meyer JJ, Lall N. Evaluation of flavonoids from Dorstenia barteri for their antimycobacterial, antigonorrheal and anti-reverse transcriptase activities. Acta Trop 2010; 116: 100-104
• 20 Chen LW, Cheng MJ, Peng CF, Chen IS. Secondary metabolites and antimycobacterial activities from the roots of Ficus nervosa . Chem Biodivers 2010; 7: 1814-1821
• 21 Mativandlela SPN, Muthivhi T, Kikuchi H, Oshima Y, Hamilton C, Hussein AA, van der Walt ML, Houghton PJ, Lall N. Antimycobacterial flavonoids from the leaf extract of Galenia africana . J Nat Prod 2009; 72: 2169-2171
• 22 Kaikabo AA, Eloff JN. Antibacterial activity of two biflavonoids from Garcinia livingstonei leaves against Mycobacterium smegmatis . J Ethnopharmacol 2011; 138: 253-255
• 23 Khlifi D, Hamdi M, El Hayouni A, Cazaux S, Souchard JP, Couderc F, Bouajila J. Global chemical composition and antioxidant and anti-tuberculosis activities of various extracts of Globularia alypum L. (Globulariaceae) leaves. Molecules 2011; 16: 10592-10603
• 24 Begum S, Wahab A, Siddiqui BS. Antimycobacterial activity of flavonoids from Lantana camara Linn. Nat Prod Res 2008; 22: 467-470
• 25 Sharma SK, Kumar G, Kapoor M, Surolia A. Combined effect of epigallocatechin gallate and triclosan on enoyl-ACP reductase of Mycobacterium tuberculosis . Biochem Biophys Res Commun 2008; 368: 12-17
• 26 Brown AK, Papaemmanouil A, Bhowruth V, Bhatt A, Dover LG, Besra GS. Flavonoid inhibitors as novel antimycobacterial agents targeting Rv0636, a putative dehydratase enzyme involved in Mycobacterium tuberculosis fatty acid synthase II. Microbiology 2007; 153: 3314-3322
• 27 Anand PK, Kaul D, Sharma M. Green tea polyphenol inhibits Mycobacterium tuberculosis survival within human macrophages. Int J Biochem Cell Biol 2006; 38: 600-609
• 28 Favela-Hernández JMJ, García A, Garza-González E, Rivas-Galindo VM, Camacho-Corona MR. Antibacterial and antimycobacterial lignans and flavonoids from Larrea tridentata . Phytother Res 2012; 26: 1957-1960
• 29 Suksamrarn A, Poomsing P, Aroonrerk N, Punjanon T, Suksamrarn S, Kongkun S. Antimycobacterial and antioxidant flavones from Limnophila geoffrayi . Arch Pharm Res 2003; 26: 816-820
• 30 Kim CE, Griffiths WJ, Taylor PW. Components derived from Pelargonium stimulate macrophage killing of Mycobacterium species. J Appl Microbiol 2009; 106: 1184-1193
• 31 Lechner D, Gibbons S, Bucar F. Plant phenolic compounds as ethidium bromide efflux inhibitors in Mycobacterium smegmatis . J Antimicrob Chemother 2008; 62: 345-348
• 32 Wu MC, Peng CF, Chen IS, Tsai IL. Antitubercular chromones and flavonoids from Pisonia aculeata . J Nat Prod 2011; 74: 976-982
• 33 Lall N, Hussein AA, Meyer JJ. Antiviral and antituberculous activity of Helichrysum melanacme constituents. Fitoterapia 2006; 77: 230-232
• 34 Lall N, Das Sarma M, Hazra B, Meyer JJM. Antimycobacterial activity of diospyrin derivatives and a structural analogue of diospyrin against Mycobacterium tuberculosis in vitro . J Antimicrob Chemother 2003; 51: 435-438
• 35 Hazra B, Sur P, Roy DK, Sur B, Banerjee A. Biological activity of diospyrin towards Ehrlich ascites carcinoma in Swiss A mice. Planta Med 1984; 51: 295-297
• 36 Weigenand O, Hussein AA, Lall N, Meyer JJM. Antibacterial activity of naphthoquinones and triterpenoids from Euclea natalensis root bark. J Nat Prod 2004; 67: 1936-1938
• 37 Mahapatra A, Mativandlela SPN, Binneman B, Fourie PB, Hamilton CJ, Meyer JJM, van der Kooy F, Houghton P, Lall N. Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase. Bioorg Med Chem 2007; 15: 7638-7646
• 38 Bapela NB, Lall N, Fourie PB, Franzblau SG, Van Rensburg CEJ. Activity of 7-methyljuglone in combination with antituberculous drugs against Mycobacterium tuberculosis . Phytomedicine 2006; 13: 630-635
• 39 Prajoubklang A, Sirithunyalug B, Charoenchai P, Suvannakad R, Sriubolmas N, Piyamongkol S, Kongsaeree P, Kittakoop P. Bioactive deoxypreussomerins and dimeric naphthoquinones from Diospyros ehretioides fruits: deoxypreussomerins may not be plant metabolites but may be from fungal epiphytes or endophytes. Chem Biodivers 2005; 2: 1358-1367
• 40 Chen JJ, Lin WJ, Shieh PC, Chen IS, Peng CF, Sung PJ. A new long-chain alkene and antituberculosis constituents from the leaves of Pourthiaea lucida . Chem Biodivers 2010; 7: 717-721
• 41 Badoni R, Semwal DK, Kothiyal SK, Rawat U. Chemical constituents and biological applications of the genus Symplocos . J Asian Nat Prod Res 2010; 12: 1069-1080
• 42 León-Díaz R, Meckes M, Said-Fernández S, Molina-Salinas GM, Vargas-Villarreal J, Torres J, Luna-Herrera J, Jiménez-Arellanes A. Antimycobacterial neolignans isolated from Aristolochia taliscana . Mem Inst Oswaldo Cruz 2010; 105: 45-51
• 43 Chen JJ, Chou ET, Peng CF, Chen IS, Yang SZ, Huang HY. Novel epoxyfuranoid lignans and antitubercular constituents from the leaves of Beilschmiedia tsangii . Planta Med 2007; 73: 567-571
• 44 Stavri M, Mathew KT, Bucar F, Gibbons S. Pangelin, an antimycobacterial coumarin from Ducrosia anethifolia . Planta Med 2003; 69: 956-959
• 45 Chiang CC, Cheng MJ, Peng CF, Huang HY, Chen IS. A novel dimeric coumarin analog and antimycobacterial constituents from Fatoua pilosa . Chem Biodivers 2010; 7: 1728-1736
• 46 Esquivel-Ferriño PC, Favela-Hernández JMJ, Garza-González E, Waksman N, Rios MY, Camacho-Corona MR. Antimycobacterial activity of constituents from Foeniculum vulgare Var. Dulce grown in Mexico. Molecules 2012; 17: 8471-8482
• 47 Alanís-Garza B, Salazar-Aranda R, Ramírez-Durón R, Garza-González E, Waksman TN. A new antimycobacterial furanolignan from Leucophyllum frutescens . Nat Prod Commun 2012; 7: 597-598
• 48 Coy ED, Cuca LE, Sefkow M. Macrophyllin-type bicyclo[3.2.1]octanoid neolignans from the leaves of Pleurothyrium cinereum . J Nat Prod 2009; 72: 1245-1248
• 49 Baquero E, Quiñones W, Ribon W, Caldas ML, Sarmiento L, Echeverri F. Effect of an Oxadiazoline and a Lignan on Mycolic Acid Biosynthesis and Ultrastructural Changes of Mycobacterium tuberculosis . Tuberc Res Treat 2011; 2011: 986409
• 50 Torres-Romero D, Jiménez IA, Rojas R, Gilman RH, López M, Bazzocchi IL. Dihydro-β-agarofuran sesquiterpenes isolated from Celastrus vulcanicola as potential anti-Mycobacterium tuberculosis multidrug-resistant agents. Bioorg Med Chem 2011; 19: 2182-2189
• 51 Jin J, Zhang JY, Guo N, Sheng H, Li L, Liang JC, Wang XL, Li Y, Liu MY, Wu XP, Yu L. Farnesol, a potential efflux pump inhibitor in Mycobacterium smegmatis . Molecules 2010; 15: 7750-7762
• 52 Dettrakul S, Surerum S, Rajviroongit S, Kittakoop P. Biomimetic transformation and biological activities of globiferin, a terpenoid benzoquinone from Cordia globifera . J Nat Prod 2009; 72: 861-865
• 53 Singh S, Kumar JK, Saikia D, Shanker K, Thakur JP, Negi AS, Banerjee S. A bioactive labdane diterpenoid from Curcuma amada and its semisynthetic analogues as antitubercular agents. Eur J Med Chem 2010; 45: 4379-4382
• 54 Sutthivaiyakit S, Mongkolvisut W, Prabpai S, Kongsaeree P. Diterpenes, sesquiterpenes, and a sesquiterpene-coumarin conjugate from Jatropha integerrima . J Nat Prod 2009; 72: 2024-2027
• 55 Scher JM, Schinkovitz A, Zapp J, Wang Y, Franzblau SG, Becker H, Lankin DC, Pauli GF. Structure and anti-TB activity of trachylobanes from the liverwort Jungermannia exsertifolia ssp. cordifolia . J Nat Prod 2010; 73: 656-663
• 56 Molina-Salinas GM, Rivas-Galindo VM, Said-Fernández S, Lankin DC, Muñoz MA, Joseph-Nathan P, Pauli GF, Waksman N. Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens . J Nat Prod 2011; 74: 1842-1850
• 57 Tan MA, Takayama H, Aimi N, Kitajima M, Franzblau SG, Nonato MG. Antitubercular triterpenes and phytosterols from Pandanus tectorius Soland. var. laevis . J Nat Med 2008; 62: 232-235
• 58 Rijo P, Simões MF, Francisco AP, Rojas R, Gilman RH, Vaisberg AJ, Rodríguez B, Moiteiro C. Antimycobacterial metabolites from Plectranthus: royleanone derivatives against Mycobacterium tuberculosis strains. Chem Biodivers 2010; 7: 922-932
• 59 Truong NB, Pham CV, Doan HTM, Nguyen HV, Nguyen CM, Nguyen HT, Zhang HJ, Fong HHS, Franzblau SG, Soejarto DD, Chau MV. Antituberculosis cycloartane triterpenoids from Radermachera boniana . J Nat Prod 2011; 74: 1318-1322
• 60 Gua JQ, Wang Y, Franzblau SG, Montenegro G, Timmermann BN. Constituents of Quinchamalium majus with potential antitubercular activity. Z Naturforsch C 2004; 59: 797-802
• 61 Bamuamba K, Gammon DW, Meyers P, Dijoux-Franca MG, Scott G. Anti-mycobacterial activity of five plant species used as traditional medicines in the Western Cape Province (South Africa). J Ethnopharmacol 2008; 117: 385-390
• 62 Ge F, Zeng F, Liu S, Guo N, Ye H, Song Y, Fan J, Wu X, Wang X, Deng X, Jin Q, Yu L. In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis . J Med Microbiol 2010; 59: 567-572
• 63 Deng JZ, Starck SR, Hecht SM. Pentacyclic triterpenoids from Freziera sp. that inhibit DNA polymerase β . Bioorg Med Chem 2000; 8: 247-250
• 64 Saikia D, Parihar S, Chanda D, Ojha S, Kumar JK, Chanotiya CS, Shanker K, Negi AS. Antitubercular potential of some semisynthetic analogues of phytol. Bioorg Med Chem Lett 2010; 20: 508-512
• 65 Deng S, Wang Y, Inui T, Chen SN, Farnsworth NR, Cho S, Franzblau SG, Pauli GF. Anti-TB polyynes from the roots of Angelica sinensis . Phytother Res 2008; 22: 878-882
• 66 Chang CP, Chang HS, Peng CF, Lee SJ, Chen IS. Antitubercular resorcinol analogs and benzenoid C-glucoside from the roots of Ardisia cornudentata . Planta Med 2011; 77: 60-65
• 67 Changtam C, Hongmanee P, Suksamrarn A. Isoxazole analogs of curcuminoids with highly potent multidrug-resistant antimycobacterial activity. Eur J Med Chem 2010; 45: 4446-4457
• 68 Mata R, Morales I, Pérez O, Rivero-Cruz I, Acevedo L, Enriquez-Mendoza I, Bye R, Franzblau S, Timmermann B. Antimycobacterial compounds from Piper sanctum . J Nat Prod 2004; 67: 1961-1968
• 69 Tuntiwachwuttikul P, Phansa P, Pootaeng-On Y, Taylor WC. Chemical constituents of the roots of Piper sarmentosum . Chem Pharm Bull (Tokyo) 2006; 54: 149-151
• 70 Noro JC, Barrows LR, Gideon OG, Ireland CM, Koch M, Matainaho T, Piskaut P, Pond CD, Bugni TS. Tetrahdroxysqualene from Rhus taitensis shows antimycobacterial activity against Mycobacterium tuberculosis . J Nat Prod 2008; 71: 1623-1624
• 71 Gröblacher B, Kunert O, Bucar F. Compounds of Alpinia katsumadai as potential efflux inhibitors in Mycobacterium smegmatis . Bioorg Med Chem 2012; 20: 2701-2706
• 72 Sethiya NK, Patel MB, Mishra SH. Phytopharmacologic aspects of Canscora decussata Roem and Schult. Pharmacogn Rev 2010; 4: 49-57