Lapachol and its congeners as anticancer agents: a review

Ali S, Singh P, Thomson RH (1980) Naturally occurring quinones. Part 28. Sesquiterpenoid quinones and related compounds from Hibiscus tiliaceus. J Chem Soc Perkin Trans 1:257–259

Awang DVC, Kindack D, Dawson BA (1986) Tandem high-performance liquid chromatography methods for resolution of lapachol and related naphthaquinones. J Chromat 368:439–443

Bakhat A, Itrat F, Abdul M et al (2010) New glycosidic constituents of Abutilon pakistanicum. Helv Chim Acta 93:2245–2250

Balassiano IT, De Paulo SA, Henriques Silva N et al (2005) Demonstration of the lapachol as a potential drug for reducing cancer metastasis. Oncol Rep 13:329–333

Bhatia BML, Vohra N (1982) Kinetic studies of the nonisothermal decomposition of metal chelates of lapachol with calcium (II), barium (II), and lead (II). Thermochim Acta 53:361–364

Block JB, Serpick AA, Miller VV et al (1974) Early clinical studies with lapachol (NSC-11905). Cancer Chemother Rep 4:27–28

Bodini ME, Arancibia V (1989) Manganese complexes with 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol). Redox chemistry and spectroscopy in dimethyl sulfoxide. Polyhedron 8:1407–1412

Bournot K (1914) Separation of lapachol from the heartwood of Avicennia tomentosa. Archiv Pharm 251:351–354

Burnett AR, Thomson RH (1967) Naturally occurring quinones. XII. Extractives from Tabebuia avellanedae. J Chem Soc C 2100–2104

Burnett AR, Thomson RH (1968) Naturally occurring quinones. XII. Extractives from Tabebuia chrysantha and other Bignoniaceae. J Chem Soc C 850–853

Cannon JR, Joshi KR, McDonald IA et al (1975) Structures of nine quinones isolated from two Conospermum species. Tetrahedron Lett 32:2795–2798

Chauhan AK, Dobhal MP, Uniyal PN (1988) Phytochemical investigation of Catalpa longissima. Herba Pol 34:3–5

Chen CC, Lee MH (1986) Constituents of Markhamia hildebrandtii (Baker) Sprague and their antitumor activity. Huaxue 44:61–64

Cooke RG, Macbeth AK, Winzer FL (1939) Absorption spectra of some naturally occurring naphthoquinones and their derivatives. J Chem Soc 878–884

Costa WF, Oliveira AB, Nepomuceno JC (2011) Lapachol as an epithelial tumor inhibitor agent in Drosophila melanogaster heterozygote for tumor suppressor gene wts. Genet Mol Res 10:3236–3245

da Consolaçao M, Linardi F, de Oliveira MM et al (1975) A lapachol derivative active against mouse lymphocytic leukemia P-388. J Med Chem 18:1159–1161

da Silva AJ, Buarque CD, Brito FV et al (2002) Synthesis and preliminary pharmacological evaluation of new (±)1,4-naphthoquinones structurally related to lapachol. Bioorg Med Chem 10:2731–2738

da Silva MN, da Souza MCBV, Ferreira VF et al (2003) Synthesis of new aldehyde derivatives from β-lapachone and nor-β-lapachone. Arkivoc 156

da Silveira JC, Gottlieb OR, de Oliveira GG (1975) Chemistry of Brazilian Bignoniaceae. 1. Zeyherol, a dilignol from Zeyheria digitalis. Phytochemistry 14:1829–1830

Dawson BA, Girard M, Kindack D et al (1989) Carbon-13 NMR of lapachol and some related naphthoquinone. Magn Res Chem 27:1176–1177

de Lima OG, D’Albuquerque IL, de Lima CG et al (1962) Antibiotic substances in higher plants. XX. Antimicrobial activity of some derivatives of lapachol as compared with xyloidone, a new natural o-naphthoquinone isolated from extracts of heartwood of Tabebuia avellanedae. Rev Inst Antibiot Univ Recife 4:3–17

de Oliveira LG, Silva MM, de Paula FCS et al (2011) Antimony(V) and bismuth(V) complexes of lapachol: synthesis, crystal structure and cytotoxic activity. Molecules 16:10314–10323

de Sousa JR, Silva GDF, Miyakoshi T et al (2006) Constituents of the root wood of Austroplenckia populnea var. ovata. J Nat Prod 69:1225–1227

Dohnal B (1976) Investigations of some metabolites of Tecoma stans Juss. Callus tissue II. Chromatograqphic analysis of alkaloid and quinone compounds. Acta Soc Bot Pol 45:369–381

Duarte DS, Dolabela MF, Salas CE et al (2000) Chemical characterization and biological activity of Macfadyena unguis-cati (Bignoniaceae). J Pharm Pharmacol 52:347–352

Eyong KO, Krohn K, Hussain H et al (2005) Newbouldiaquinone and newbouldiamide: a new naphthoquinone-anthraquinone coupled pigment and a new ceramide from Newboldia laevis. Chem Pharm Bull 53:616–619

Eyong KO, Folefoc GN, Kuete V et al (2006) Newbouldiaquinone A: a naphthoquinone-anthraquinone ethere coupled pigment, as a potential antimicrobial and antimalarial agent from Newboldia laevis. Phytochemistry 67:605–609

Eyong KO, Kumar PS, Kuete V et al (2008) Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other naphthoquinone derivatives from lapachol. Bioorg Med Chem Lett 18:5387–5390

Farfan RA, Molina JR, Ottavianelli E et al (2006) Infrared band assignment of lapachol by means of comparative theoretical and experimental studies. Inf Technol 17:63–66

Farfan RA, Espindola JA, Martinez MA et al (2009) Synthesis and crystal structure of a new lapacholate complex with nickel(II), [Ni(Lap)2(DMF)(H2O)]. J Coord Chem 62:3738–3744

Ferreira SB, Rodrigues da Rocha D, Carneiro JWM et al (2011) A new method to prepare 3-alkyl-2-hydroxy-1,4-naphthoquinones: synthesis of lapachol and phthiocol. Synlett 1551–1554

Fieser LF (1927) the alkylation of hydroxynaphthoquinone. A synthesis of lapachol. J Am Chem Soc 49:857–864

Finkel JM, Harrison SD Jr (1969) Fluorimetric method for the determination of lapachol in serum. Anal Chem 41:1854–1855

Fonseca SGC, da Silva LBL, Castro RF et al (2004) Validation of the analytical methodology for the determination of lapachol in solutions by HPLC. Quim Nova 27:157–159

Galotta ALQA, Bonaventura MAD, Lima LARS (2008) Antioxidant and cytotoxic activities of “acai” (Euterpe precatoria Mart.). Quim Nova 31:1427–1430

Ghogomu-Tih R, Nyasse B, Tsamo E et al (1986) Chemical constituents of the stem heart wood of Stereospermum kunthianum. Planta Med 1986:342

Girard M, Kindack D, Dawson BA et al (1988) Naphthoquinones constituents from Tabebuia spp. J Nat Prod 51:1023–1024

Gomez Castellanos JR, Prieto JM, Heinrich M (2009) Red lapacho (Tabebula impetiginosa). A global ethnopharmacologically commodity? J Ethnopharmacol 121:1–13

Govindachari TR, Patankar SJ, Viswanathan N (1971) Isolation and structure of two new dihydroisocoumarins from Kigelia pinnata. Phytochemistry 10:1603–1606

Grazziotin JD, Schapoval EES, Chaves CG et al (1992) Phytochemical and analgesic investigation of Tabebuia chrysotricha. J Ethnopharmacol 36:249–251

Grolig J, Wagner R (2005) Naphthoquinones. In: Ullmann’s encyclopedia of industrial chemistry. Wiley-VCH, Weinheim

Gupta SR, Malik KK, Seshadri TR (1969) Lapachol from the heartwood of Tecoma undulata and a not on its reaction. Ind J Chem 7:457–459

Hooker SC (1892) The constitution of lapachic acid (lapachol) and its derivatives. J Chem Soc 61:611–650

Houghton P, Pandev R, Hawkes JE (1994) Naphthoquinones and an alkaloid from the roots of Newboldia laevis. Phytochemistry 35:1602–1603

Huang P, Karagianis G, Wei S et al (2004) α-Lapachone and other naphthoquinones from the heartwood of Paulownia kawakamii. Biochem Syst Ecol 32:1047–1049

Inoue K, Chen CC, Inouye H et al (1981) Quinones and related compounds in higher plants. Part 16. Naphthoquinones from Radermachera sinica Hemsl. (Bignoniaceae). J Chem Soc Perkin Trans 1:2764–2770

Ito C, Katsuno S, Kondo Y et al (2000) Chemical constituents of Avicenna alba. Isolation and structural elucidation of new naphthoquinones and their analogues. Chem Pharm Bull 48:339–343

Jacobsen N, Torssell K (1973) Synthesis of naturally occurring quinones. Alkylation with the silver ion-peroxydisulfate-carboxylic acid system. Acta Chem Scand 27:3211–3216

Jacome RLRP, de Oliveira AB, Raslan DS et al (1999) Analysis of naphthoquinones in Zeyheria montana crude extracts. Quim Nova 22:175–177

Jassabi AR, Mehrdad M, Eghtesadi F et al (2006) Novel rearranged abietane diterpenoids from the roots of Salvia sahendica. Chem Biodiv 3:916–922

Joshi KC, Singh LB (1974) Quinonoid and other constituents from the heartwood of Tecomella undulate. Phytochemistry 13:663–664

Joshi KC, Prakash L, Singh P (1973a) Quinones and other constituents from Phyllarthron comorense. Phytochemistry 12:469–470

Joshi KC, Prakash L, Singh P (1973b) Quinones and other constituents from Tabebuia rosea. Phytochemistry 12:942–943

Joshi KC, Bansal RK, Singh P et al (1975) Components of the stem barks of Phyllarthron comorense and Jacaranda mimosaefolia and the roots of Desmodium pulchellum. Ind J Chem 13:869–870

Joshi KC, Singh P, Singh G (1976) Crystalline components of roots of Phyllarthron comorense DC and of stem bark of Tabebuia rosea DC. Ind J Chem B 14:637–638

Joshi KC, Bansal RK, Patni R (1977a) Chemical examination of the roots of Stereospermum suaveolens DC. J Ind Chem Soc 54:648–649

Joshi KC, Prakash L, Shah RK (1977b) Chemical examination of the roots of Tabebuia rosea and Oroxylum indicum. Planta Med 257–258

Joshi KC, Singh P, Pardasani RT (1977c) Quinones and other constituents from the roots of Tecomella undulate. Planta Med 14–16

Joshi KC, Singh P, Singh G (1977d) Chemical examination of Tecomella undulata Seem. Curr Sci 46:145–146

Joshi KC, Singh P, Pardasani RT (1978) Chemical constituents from the stem heartwood of Markhamia stipulata. Planta Med 219–221

Joshi KC, Singh P, Pardasani RT et al (1979) Quinones and other constituents from Heterophragma adenophyllum. Planta Med 1979:60–63

Joshi KC, Singh P, Taneja S (1981) Crystalline components of the stem heartwood of Randia dumatorium and Kigelia pinnata. J Ind Chem Soc 58:825–826

Joshi KC, Singh P, Sharma MC (1985) Quinones and other constituents of Markhamia platycalyx and Bignonia unguiscati. J Nat Prod 48:145

Joshi KC, Sharma AK, Singh P (1986) A new ferulic ester from Tecomella undulata. Planta Med 71–72

Kawasaki Y, Goda Y, Yoshihira K (1992) The mutagenic constituents of Rubia tinctorum. Chem Pharm Bull 40:1504–1509

Kazantzi G, Malamidou-Xenikaki E, Spyroudis S (2007) Palladium-catalyzed allylation of 2-hydroxy-1,4-naphthoquinone. Application to the preparation of lapachol. Synlett 427–430

Khan RM, Mlungwana SM (1998) 5-Hydroxylapachol: a cytotoxic agent from Tectona grandis. Phytochemistry 50:439–442

Khan MR, Mlungwana SM (1999) γ-Sitosterol, a cytotoxic sterol from Markhamia zanzibarica and Kigelia Africana. Fitoterapia 70:111–112

Kishore N, Mishra BB, Tiwari VK et al (2010) Difuranonaphtoquinones from Plumbago zeylanica roots. Phytochem Lett 3:62–65

Krustrak D (2001) Taheebo-Lapacho-Tabebuia impetiginosa. Farm Glasn 57:215–222

Kumar US, Tiwari AK, Reddy SV et al (2005) Free-radical scavenging and xanthine oxidase inhibitory constituents from Stereospermum personatum. J Nat Prod 68:1615–1621

Lemos TLG, Monte FJQ, Kellen A et al (2007) Quinones from plants of northeastern Brazil: structural diversity, chimica transformations, NMR data and biological activities. Nat Prod Res 21:529–550

Lima CSA, de Amorim ELC, Nascimento SC et al (2005) Cytotoxic pyranonaphthoquinones from Melloa quadrivalvis (Bignoniaceae). Nat Prod Res 19:217–222

Lukmandaru G, Ashitani T, Takahashi K (2009) Color and chemical characterization of partially black-streaked heartwood in teak (Tectona grandis). J Forestry Res 20:377–380

Maeda M, Murakami M, Takegami T et al (2008) Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol. Toxicol Appl Pharmacol 229:232–238

Maia RC, Vasconcelos FC, de Sá Bacelar T et al (2011) LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]: a novel class of agent with high apoptotic effect in chronic myeloid leukemia cells. Invest New Drugs 29:1143–1155

Manners GD, Jurd L (1976) A new naphthoquinone from Tabebuia guayacan. Phytochemistry 15:225–226

Martinez MA, de Jimenez MCL, Castellano EE et al (2005) Two isostructural complexes of Co (II) and Zn (II) with lapacholate, dimethylformamide and water. J Arg Chem Soc 93:185–193

Miranda FGG, Vilar JC, Alves IAN et al (2001) Antinociceptive and antiedematogenic properties and acute toxicity of Tabebuia avellanedae Lor. Ex Griseb. Inner bark aqueous extract. BMC Pharmacol 1:6

Mol HGJ, van Dam RCJ, Zomer P et al (2011) Screening of plant toxins in food, feed, and botanicals using full-scan high-resolution (Orbitrap) mass spectrometry. Food Addit Contam A 28:1405–1423

Moreira RYO, Arruda MSP, Arruda AC et al (2006) Anthraquinones and naphthoquinones from the bark of Tectona grandis reforestation specimen. Rev Bras Farmac 16:392–396

Ngameni E, Tonle IK, Nanseu et al (2000) Voltammetry study of 2-hydroxy-3-isoprenyl-1,4-naphthoquinone using a carbon paste electrode. Electroanalysis 12:847–852

Niehues M, Barros VP, Emery FS et al (2012a) Biomimetic in vitro oxidation of lapachol: a model to predict and analyse the in vivo phase I metabolism of bioactive compounds. Eur J Med Chem 54:804–812

Niehues M, Barros VP, Emery FS et al (2012b) From in vitro to in vivo: preclinical data on the oxidative metabolism and pharmacokinetics of lapachol. Planta Med 78:PH9

Novotna P, Pacakova V, Bosakova Z et al (1999) High-performance liquid chromatographic determination of some anthraquinone and naphthoquinone dyes occurring in historical textiles. J Chromat A 863:234–241

Oesterde OA (1916) Substance accompanying lapachol in greenheart wood. Archiv Pharm 254:346–348

Oesterde OA (1917) Substance accompanying lapachol in greenheart wood. J Chem Soc 112:505

Orth H (1960) Isolation of extraneous materials from Tabebuia flavescens by extraction. Holzforsch 14:89–91

Ossowski T, Goulart MOF, de Abreu FC et al (2008) Determination of the pKa values of some biologically active and inactive hydroxyquinones. J Braz Chem Soc 19:175–183

Parrilha GL, Vieira RP, Campos PP et al (2012) Coordination of lapachol to bismuth(III) improves its anti-inflammatory and anti-angiogenic activities. Biometals 25:55–62

Paternò E (1882) Ricerche sull’acido lapachico. Gazz Chim It 12:337–392

Pettit GR, Houghton LE (1971) Synthesis of hydroxyhydrolapachol and lapachol. J Chem Soc C 3:509–511

Pires SMG, de Paula R, Simoes MMQ et al (2011) Novel biomimetic oxidation of lapachol with H2O2 catalysed by a manganese(III) porphyrin complex. RSC Advances 1:1195–1199

Prakash L, Garg MG (1981) Chemical constituents of the roots of Millingtonia hortensis Linn. and Acacia nilotica (Linn.) Del. J Ind Chem Soc 58:96–97

Prakash L, Singh R (1980a) Phytochemical screening of Bignonia gracilis Lodd. (Bignoniaceae). Pharmazie 35:649–650

Prakash L, Singh R (1980b) Chemical constituents of the stem bark and stem heartwood of Dolichandrone crispa Seem. Pharmazie 35:122–123

Prakash L, Singh R (1980c) Chemical constituents of stem bark and root heartwood of of Tabebuia pentaphylla Hemsl. (Bignoniaceae). Pharmazie 35:813

Prakash L, Singh R (1981) Chemical examination of the leaves and stem heartwood of Tabebuia pentaphylla Hemsl. (Bignoniaceae). J Ind Chem Soc 58:1122–1123

Purushothaman KK, Natarajan RK (1974) Chemical examination of Patala (Stereospermum tetragonum DC). J Res Ind Med 9:107–108

Rennie EH (1895) A colouring matter from Lomatia illicifolia and Lomatia longifolia. J Chem Soc 67:784–793

Rodrigues SV, Viana LM, Baumann W (2006) UV/Vis spectra and solubility of some naphthoquinones, and the extraction behaviour of plumbagin from Plumbago scandens roots in supercritical CO2. Anal Bioanal Chem 385:895–900

Rodriguez C, Erika DC, Torrenegra R (1999) Antifungal and antibacterial furanonaphthoquinones from Tabebuia coralibe. Rev Lat Quim 27:89–93

Rohatgi BK, Gupta RB, Roy D et al (1983) Quinones from Tecoma pentaphylla: constitution of tecomaquinones I and II. Ind J Chem B 22:886–889

Sagrero-Nievese L (1986) Isolation of lapachol from Diphysa robinoides. J Nat Prod 49:547

Salustiano EJS, Netto CD, Fernandes RF et al (2010) Comparison of the cytotoxic effect of lapachol, alpha-lapachone and pentacyclic 1,4-naphthoquinones on human leukemic cells. Invest New Drugs 28:139–144

Sanderman W, Simatupang MH, Wenderborn W (1968) New quinones from the heartwood of Paratecoma peroba. Naturwiss 55:38

Sandermann W, Simatupang MH (1964) Constituents from teak (Tectona grandis) II. Constitution and synthesis of tectol and dehydrotectol. Chem Ber 97:588–597

Sandermann W, Simatupang MH (1965) New quinones from Tectona grandis. Naturwiss 52:262–263

Santan DP, Fonseca SGC, Bedor DCG et al (2008) Application of thermal analysis in the development and characterization of PLGA microparticles containing lapachol. Rev Ciencias Farm Bas Aplic 29:261–266

Sawhney SS, Matta SD, Jain R et al (1983) Investigation on the interaction of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol) with copper(II) and iron(II). Thermochim Acta 70:367–371

Schmeda-Hirschmann G, Papastergiou F (2003) Naphthoquinone derivatives and lignans from the Paraguayan crude drug Tayi pyta (Bignoniaceae). Zeitsch Naturforsch C 58:495–501

Shetgiri NP, Kokitkar SV, Sawant SN (2001) Radermachera xylocarpa: the highly efficient source of lapachol and synthesis of its derivatives. Acta Pol Pharm 58:133–135

Singh P, Singh A (1980) Quinonoid constituents of the bark of Markhamia tipulate Wall. Pharmazie 35:701–702

Singh P, Prakash L, Joshi KC (1972) Lapachol and other constituents from the Bignoniaceae. Phytochemistry 11:1498

Singh P, Jain S, Bhargava S (1989) A 1,4-anthraquinone derivative from Tectona grandis. Phytochemistry 28:1258–1259

Singh P, Natani K, Jain S et al (2006) Microwave-assisted rapid cyclization of lapachol, a main constituents of Heterophragma adenophyllum. Nat Prod Res 20:207–212

Singh P, Khandelwal P, Hara N et al (2008a) Radermachol and naphtoquinone derivatives from Tecomella tipulat: complete 1H and 13C NMR assignments of radermachol with the aid of computational 13C shift prediction. Ind J Chem B 47:1865–1870

Singh P, Pandey D, Mathur J et al (2008b) Barleriaquinone-l from the heartwood of Tectona grandis Linn. J Ind Chem Soc 85:1060–1063

Singh P, Khandelwai P, Sharma K et al (2010) Cetyl triacontanoate and other constituents from Acacia jacquemontii and Kigelia pinnata. J Ind Chem Soc 87:1403–1407

Steinert J, Khalaf H, Rimpler M (1996) High performance liquid chromatography separation of some naturally occurring naphthtoquinones and anthraquinones. J Chrom A 723:206–209

Sun JS, Geiser AH, Frydman B (1998) A preparative synthesis of lapachol and related naphthoquinones. Tetrahedron Lett 39:8221–8224

Velasquez J, Rojas LB, Usubillaga A (2004) Antifungal activity of naphthoquinone from Tabebuia serratifolia Vahl. Nicholson Ciencia 12:64–69

Vessecchi R, Emery FS, Galembeck SE et al (2010) Fragmentation studies and electrospray ionization mass spectrometry of lapachol: protonated, deprotonated and cationized species. Rapid Commun Mass Spectr 24:2101–2108

Viana EP, Santa Rosa RS, Almeida SSMS et al (1999) Constituents of the stem bark of Bauhinia guianensis. Fitoterapia 70:111–112

Viana LM, Freitas MR, Rodrigues SV et al (2003) Extraction of lapachol from Tabebuia avellanedae wood with supercritical CO2: an alternative to soxhlet extraction? Braz J Chem Eng 20:317–325

Vidal-Tessier AM, Delaveau P, Champion B et al (1988) Lipophilic quinones of the trunk wood of Tabebuia serratifolia. Ann Pharm Franc 46:55–57

Villegas JR, Amato S, Castro I et al (1995) 4-Aryltetraline tipul and furanonaphthoquinone from Tabebuia palmeri wood. Fitoterapia 66:281–282

Wagner H, Kreher B, Lotter H et al (1989) Structure determination of new isomeric naphtha[2,3-b]furan-4,9-diones from Tabebuia avellanedae by the selective INEPT technique. Helv Chim Acta 72:659–667

Windeisen E, Klassen A, Wegener G (2003) On the chemical characterization of plantation teakwood from Panama. Holz Roh Werkst 61:416–418

Zani C, de Oliveira AB, de Oliveira GG (1991) Furanonaphthoquinones from Tabebuia ochracea. Phytochemistry 30:2379–2381

Zhou J, Duan L, Chen H et al (2009) Atovaquone derivatives as potent cytotoxic and apoptosis inducing agents. Bioorg Med Chem Lett 19:5091–5094

Zoghbi MGB, Oliveira J, Guilhon GMSP (2009) The genus Mansoa (Bignoniaceae): a source of organosulfur compounds. Rev Bras Farmac 19:795–804