Cytotoxic, Anti-inflammatory, and Leishmanicidal Activities of Diterpenes Isolated from the Roots of Caesalpinia pulcherrima

Abstract

A phytochemical investigation on the chloroform extract of Caesalpinia pulcherrima roots led to the isolation of ten known furanocassane diterpenoids, vouacapen-5α-ol (1), 8,9,11,14-didehydrovouacapen-5α-ol (2), 6β-cinnamoyl-7β-hydroxyvouacapen-5α-ol (3), pulcherrin A (4), pulcherrin B (5), pulcherrin J (6), pulcherrimin A (7), pulcherrimin B (8), pulcherrimin C (9), and pulcherrimin E (10). Chemical transformation of 3 and 7 gave compounds 6β-hydroxyisovouacapenol C (11), 6β-cinnamoyl-7β-acetoxyvouacapen-5α-ol (12), and pulcherrimin D (13). Cytotoxicity of compounds 1-13 was evaluated against three cancer cell lines (MCF-7, HeLa, and PC-3). Anti-inflammatory potential of the compounds was evaluated via the oxidative burst assay using a luminol-amplified chemiluminescence technique. Leishmanicidal activity was tested against promastigotes of Leishmania major in vitro. Compounds 3, 4, 8, 9, and 10 were found active against all three cancer cell lines with IC₅₀s ranging from 7.02 ± 0.31 to 36.49 ± 1.39 µM. Compounds 8 and 13 exhibited a potent inhibitory effect on reactive oxygen species generated from human whole blood phagocytes (IC₅₀ = 15.30 ± 1.10 µM and 8.00 ± 0.80 µM, respectively). Compounds 3, 9, and 13 showed significant activity against promastigotes of L. major (IC₅₀ = 65.30 ± 3.20, 58.70 ± 2.80, and 55.90 ± 2.40 µM, respectively).

Key words

Caesalpinia pulcherrima - Caesalpiniaceae - cassane diterpenoids - cytotoxicity - cancer cells - leishmanicidal activity - anti-inflammatory activity

• References

• 1 Srinivas KVNS, Rao YK, Mahender I, Das B, Krishna KVSR, Kishore KH, Murty USN. Flavonoids from Caesalpinia pulcherrima . Phytochemistry 2003; 63: 789-793
• 2 Chiang LC, Chiang W, Liu MC, Lin CC. In vitro antiviral activity of Caesalpinia pulcherrima and its related flavonoids. J Antimicrob Chemother 2003; 52: 194-198
• 3 Mahesh G, Ramkanth S, Saleem MTS. Anti-inflammatory drugs from medicinal plants: a comprehensive review. Int J Rev Life Sci 2011; 1: 1-10
• 4 Roach JS, McLean S, Reynolds WF, Tinto WF. Cassane diterpenoids of Caesalpinia pulcherrima . J Nat Prod 2003; 66: 1378-1381
• 5 Promsawan N, Kittakoop P, Boonphong S, Nongkunsarn P. Antitubercular cassane furanoditerpenoids from the roots of Caesalpinia pulcherrima . Planta Med 2003; 69: 776-777
• 6 Sudhakar M, Rao CV, Rao PM, Raju DB, Venkateswarlu Y. Antimicrobial activity of Caesalpinia pulcherrima, Euphorbia hirta and Asystasia Gangeticum . Fitoterapia 2006; 77: 378-380
• 7 Pawar CR, Mutha RE, Landge AD, Jadhav RB, Surana SJ. Antioxidant and cytotoxic activities of Caesalpinia pulcherrima wood. Ind J Biochem Biophy 2009; 46: 198-200
• 8 Patel SS, Verma NK, Chatterjee C, Gauthaman K. Screening of Caesalpinia pulcherrima Linn. flowers for analgesic and anti-inflammatory activities. Int J Appl Res Nat Prod 2010; 3: 1-5
• 9 Sharma V, Rajani GP. Evaluation of Caesalpinia pulcherrima Linn. for anti-inflammatory and antiulcer activities. Ind J Pharmacol 2011; 43: 168-171
• 10 Venkatesalu V, Gopalan N, Pillai CR, Singh V, Chandrasekaran M, Senthilkumar A, Chandramouli N. In vitro antiplasmodial activity of some traditionally used medicinal plants against Plasmodium falciparum . Parasitol Res 2012; 111: 497-501
• 11 Kumbhare M, Sivakumar T, Kalantri M, Mahajan V. Investigation of anthelmintic activity of pods of Caesalpinia pulcherrima . J Pharm Res Opin 2012; 2: 63-65
• 12 WHO. Cancer. World Health Organization; 2010. Available at http://www.who.int/cancer/en Accessed April 12, 2016
• 13 Chu E, Sartorelli AC. Cancer chemotherapy. In: Katzung BG, editor Basic and clinical pharmacology, 9th ed. U.S.A. Portland, OR: McGraw-Hill; 2004: 888-930
• 14 Chen Y, Junger WG. Measurement of oxidative burst in neutrophils. Methods Mol Biol 2012; 844: 115-124
• 15 Root RK, Cohen MS. The microbicidal mechanisms of human neutrophils and eosinophils. Rev Infect Dis 1981; 3: 565-598
• 16 Dimitrova G, Bunkall C, Lim D, Kendrick C. Comparison of two methods for the diagnosis of chronic granulomatous disease – neutrophil oxidative burst measured by the nitroblue tetrazolium slide test versus the dihydrorhodamine 123 flow cytometric assay. N Z J Med Lab Sci 2013; 67: 45-51
• 17 Dahlgren C, Karlsson A. Respiratory burst in human neutrophils. J Immun Meth 1999; 232: 3-14
• 18 Afonso V, Chamy R, Mitrovic D, Collin P, Lomri A. Reactive oxygen species and superoxide dismutases: role in joint diseases. Joint Bone Spine 2007; 74: 324-329
• 19 Walrand S, Valeix S, Rodriguez C, Ligot P, Chassagne J, Vasson MP. Flow cytometry study of polymorphonuclear neutrophil oxidative burst: a comparison of three fluorescent probes. Clin Chim Acta 2003; 331: 103-110
• 20 Bokoch GM, Zhao T. Regulation of the phagocyte NADPH oxidase by Rac GTPase. Antiox Redox Signal 2006; 8: 1533-1548
• 21 Helfand LS, Werkmeister J, Roder JC. Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence and cytolysis. J Exp Med 1982; 156: 492-505
• 22 Lundqvist H, Dahlgren C. Isoluminol-enhanced chemiluminescence: a sensitive method to study the release of superoxide anion from human neutrophils. Free Rad Biol Med 1996; 20: 785-792
• 23 Ashford RW. The leishmaniases as emerging and reemerging zoonoses. Int J Parasitol 2000; 30: 1269
• 24 Desjeux P. The increase in risk factors for leishmaniasis. Trans R Soc Trop Med Hyg 2001; 95: 239-243
• 25 Barrett MP, Croft SL. Management of trypanosomiasis and leishmaniasis. Br Med Bull 2012; 104: 175-196
• 26 de Carvalho PB, da Arribas MAG, Ferreira EI. Braz J Pharm Sci 2002; 36: 69-96
• 27 Lozano R. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of diseases study 2010. Lancet 2012; 380: 2095-2128
• 28 Pandy S, Suryawanshi SN, Gupta S, Srivastava VML. Synthesis and antileishmanial profile of some novel terpenyl pyrimidines. Eur J Med Chem 2004; 39: 969-973
• 29 Minodier P, Parola P. Cutaneous leishmaniasis treatment. Travel Med Infect Dis 2007; 5: 150-158
• 30 Chan-Bacab MJ, Peña-Rodríguez LM. Plant natural products with leishmanicidal activity. Nat Prod Rep 2001; 18: 674-688
• 31 Kayser O, Kiderlen AF. In vitro leishmanicidal activity of naturally occurring chalcones. Phytother Res 2001; 15: 148-152
• 32 Rocha LG, Almeida JRGS, Macêdo RO, Barbosa-Filho JM. A review of natural products with antileishmanial activity. Phytomed 2005; 12: 514-535
• 33 Atta-ur-Rahman S, Atia-tul-Wahab. Choudhary MI. Discovery of leishmanicidal agents from medicinal plants. Pure Appl Chem 2008; 80: 1783-1790
• 34 McPherson DD, Che C, Cordell GA, Soejarto DD, Pezzuto JM, Fong HHS. Diterpenoids from Caesalpinia pulcherrima . Phytochemistry 1986; 25: 167-170
• 35 Patil AD, Freyer AJ, Webb RL, Zuber G, Reichwein R, Bean MF, Faucette L, Johnson RK. Pulcherrimins A–D, novel diterpene dibenzoates from Caesalpinia pulcherrima with selective activity against DNA repair-deficient yeast mutants. Tetrahedron 1997; 53: 1583-1592
• 36 Ragasa Y, Hofilena JG, Rideout JA. Furanoid diterpenes from Caesalpinia pulcherrima . J Nat Prod 2002; 65: 1107-1110
• 37 Kuroda C, Ueshino T, Nagano H. Ehrlichʼs reaction of furanoeremophilanes. Bull Chem Soc Japan 2004; 77: 1737-1740
• 38 Cheenpracha S, Srisuwan R, Karalai C, Ponglimanont C, Chantrapromma S, Chantrapromma K, Fun HK, Anjum S. Atta-ur-Rahman. Diterpenoids from stems and roots of Caesalpinia crista . Tetrahedron 2005; 61: 8656-8662
• 39 Cheenpracha S, Karalai C, Ponglimanont C, Chantrapromma K, Laphookhieo S. Cassane-type diterpenes from the seeds of Caesalpinia crista . Helv Chem Acta 2006; 89: 1062-1066
• 40 Pranithanchai W, Karalai C, Ponglimanont C, Subhadhirasakul S, Chantrapromma K. Cassane diterpenoids from the stem of Caesalpinia pulcherrima . Phytochemistry 2009; 70: 300-304
• 41 Yodsaoue O, Karalai C, Ponglimanont C, Tewtrakul S, Chantrapromma S. Pulcherrins D–R, potential anti-inflammatory diterpenoids from the roots of Caesalpinia pulcherrima . Tetrahedron 2011; 67: 6838-6846
• 42 Das B, Srinivas Y, Sudhakar C, Mahender I, Laxminarayana K, Reddy PR, Raju TV, Jakka NM, Rao JV. New diterpenoids from Caesalpinia species and their cytotoxic activity. Bioorg Med Chem Lett 2010; 20: 2847-2850
• 43 Karlsson A, Markfjall M, Stromberg N, Dahlgren C. Escherichia coli-induced activation of the neutrophil NADPH-oxidase: lipopolysaccharide and formulated peptides act synergistically to induce a release of reactive oxygen metabolites. Infect Immun 1995; 63: 4606
• 44 Karlsson A, Follin P, Leffler H, Dahlgren C. Galectin-3 activates the NADPH-oxidase in exudated but not peripheral blood neutrophils. Blood 1998; 91: 3430-3438
• 45 Scudiere DA, Shoemaker RH, Paul KD, Monks A, Tierney S, Nofziger TH, Currens MJ, Seniff D, Boyd MR. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 1988; 48: 4827-4833
• 46 Koko WS, Mesaik MA, Yousaf S, Galal M, Choundary MI. In vitro immunomodulating properties of selected Sudanese medicinal plants. J Ethnopharmacol 2008; 118: 26-34
• 47 Choudhary MI, Yousuf S, Samreen SA, Yasmeen K. Atta-ur-Rahman. Antileishmanial physalins from Physalis minima . Chem Biodiv 2005; 2: 1164-1173