Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1) in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2′,6′-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0？μg/mL (7.4？μM) and could be a lead for anti-malarial drug discovery. 1. Introduction Malaria is a vector borne disease, caused by the Plasmodium parasite. According to WHO report, there were estimated 216 million episodes of malaria in 2010, of which approximately 81%, or 174 million cases, were in the African region. There were estimated 655,000 malaria deaths in 2010, of which 91% were in Africa. Approximately 86% of malaria deaths globally were of children under 5 years of age [1]. In addition to acute disease episodes and deaths in Africa, malaria also contributes significantly to anaemia in children and pregnant women, adverse birth outcomes such as spontaneous abortion, stillbirth, premature delivery, and low birth weight, and overall child mortality. Included in the WHO report was the fact that resistance to artemisinin, a vital component of drugs used in the treatment of P. falciparum malaria, has been reported in a growing number of countries in Southeast Asia. Resistance to pyrethroids, the insecticides used in ITNs and most commonly used in IRS, has been reported in 27 countries in Africa and 41 countries worldwide [1]. Unless properly managed, such resistance potentially threatens future progress in malaria control. The search for new antimalarial drugs requires identification of new biochemical targets for drug development and development of new chemical entities [2, 3]. Epidemiological studies have provided convincing evidence that natural dietary compounds, which humans consume as food, possess many biological activities [4]. One plant food that has been shown to be therapeutic against a number of diseases is pigeon pea, Cajanus cajan L. (Fabaceae), an important grain legume crop in the tropics and subtropics. The extracts of pigeon pea are commonly used to treat diabetes, fever, dysentery, hepatitis, and measles worldwide [5, 6]. Cajanus cajan has
References
[1]
WHO, “Global Malaria Programme,” WHO, World Malaria Report. 10–16, 2011.
[2]
P. Sharma and J. D. Sharma, “Plants showing antiplasmodial activity from crude extracts to isolated compounds,” Indian Journal of Malariology, vol. 35, no. 2, pp. 57–110, 1998.
[3]
S. Schwikkard and F. R. Van Heerden, “Antimalarial activity of plant metabolites,” Natural Product Reports, vol. 19, no. 6, pp. 675–692, 2002.
[4]
A. García-Lafuente, E. Guillamón, A. Villares, M. A. Rostagno, and J. A. Martínez, “Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease,” Inflammation Research, vol. 58, no. 9, pp. 537–552, 2009.
[5]
S. Ambekar, S. C. Patil, A. P. Giri, and M. S. Kachole, “Proteinaceous inhibitors of trypsin and amylases in developing and germinating seeds of red gram (Cajanus cajan L. Millsp.),” Journal of the Science of Food and Agriculture, vol. 72, pp. 57–62, 1996.
[6]
J. K. Grover, S. Yadav, and V. Vats, “Medicinal plants of India with anti-diabetic potential,” Journal of Ethnopharmacology, vol. 81, no. 1, pp. 81–100, 2002.
[7]
E. O. Ajaiyeoba, J. S. Ashidi, D. O. Akinboye et al., “In vitro antiplasmodial and cytotoxicity activities of 6 plants from the Southwest Nigerian Ethnomedicine,” Journal of Natural Remedies, vol. 5, no. 1, pp. 1–6, 2005.
[8]
L. C. Okpako and E. O. Ajaiyeoba, “In vitro and in vivo antimalarial studies of Striga hermonthica and Tapinanthus sessilifolius extracts,” African Journal of Medicine and Medical Sciences, vol. 33, no. 1, pp. 73–75, 2004.
[9]
A. H. Fairlamb, D. C. Warhurst, and W. Peters, “An improved technique for the cultivation of Plasmodium falciparumin vitro without daily medium change,” Annals of Tropical Medicine and Parasitology, vol. 79, no. 4, pp. 379–384, 1985.
[10]
M. T. Makler and D. J. Hinrichs, “Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia,” American Journal of Tropical Medicine and Hygiene, vol. 48, no. 2, pp. 205–210, 1993.
[11]
V. P. K. Titanji, D. Zofou, and M. N. Ngemenya, “The antimalarial potential of medicinal plants used for the treatment of malaria in Cameroonian folk medicine,” African Journal of Traditional, Complementary and Alternative Medicines, vol. 5, no. 3, pp. 302–321, 2008.
[12]
T. Saitoh and S. Shibata, “New type chalcones from licorice root,” Tetrahedron Letters, vol. 50, pp. 4461–4462, 1975.
[13]
M. Chen, S. B. Christensen, L. Zhai et al., “The novel oxygenated chalcone, 2,4-dimethoxy- -butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo,” Journal of Infectious Diseases, vol. 176, no. 5, pp. 1327–1333, 1997.
[14]
S. F. Nielsen, T. Bosen, M. Larsen, K. Schonning, and H. Kromann, “Antibacterial chalcones—bioisosteric replacement of the -hydroxy group,” Bioorganic & Medicinal Chemistry, vol. 12, pp. 3047–3054, 2004.
[15]
S. F. Nielsen, M. Larsen, T. Bosen, K. Schonning, and H. Kromann, “Cationic chalcone antibiotics: design, synthesis, and mechanism of action,” Journal of Medicinal Chemistry, vol. 48, pp. 2667–2677, 2005.
[16]
S. K. Awasthi, N. Mishra, B. Kumar et al., “Potent antimalarial activity of newly synthesized substituted chalcone analogs in vitro,” Medicinal Chemistry Research, vol. 18, no. 6, pp. 407–420, 2009.
[17]
J. E. Wood, M. H. G. Munro, J. W. Blunt, N. B. Perry, J. R. L. Walker, and J. M. Ward, “Biologically active compounds from Ozothamnus leptophyllus,” New Zealand Journal of Botany, vol. 37, no. 1, pp. 167–174, 1999.
[18]
S. Cheenpracha, C. Karalai, C. Ponglimanont, S. Subhadhirasakul, and S. Tewtrakul, “Anti-HIV-1 protease activity of compounds from Boesenbergia pandurata,” Bioorganic & Medicinal Chemistry, vol. 14, no. 6, pp. 1710–1714, 2006.
[19]
M. Liu, P. Wilairat, S. L. Croft, A. L. Tan, and M. L. Go, “Structure-activity relationships of antileishmanial and antimalarial chalcones,” Bioorganic & Medicinal Chemistry, vol. 11, pp. 2729–2738, 2003.
[20]
T. P. Robinson, R. B. Hubbard, T. J. Ehlers, J. L. Arbiser, D. J. Goldsmith, and J. P. Bowen, “Synthesis and biological evaluation of aromatic enones related to curcumin,” Bioorganic & Medicinal Chemistry, vol. 13, no. 12, pp. 4007–4013, 2005.
[21]
Y. K. Rao, F. S. Fang, and Y. M. Tzeng, “Differential effects of synthesized -oxygenated chalcone derivatives: modulation of human cell cycle phase distribution,” Bioorganic & Medicinal Chemistry, vol. 122, pp. 2679–2686, 2004.
[22]
M. Chen, T. G. Theander, S. B. Christensen, L. Hviid, L. Zhai, and A. Kharazmi, “Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection,” Antimicrobial Agents and Chemotherapy, vol. 38, no. 7, pp. 1470–1475, 1994.
[23]
J. N. Dominguez, C. Leon, J. Rodrigues, N. G. De Dominguez, J. Gut, and P. J. Rosenthal, “Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives,” Journal of Medicinal Chemistry, vol. 48, pp. 3654–3658, 2005.
[24]
A. Valla, B. Valla, D. Cartier et al., “New syntheses and potential antimalarial activities of new “retinoid-like chalcones“,” European Journal of Medicinal Chemistry, vol. 41, no. 1, pp. 142–146, 2006.
[25]
T. Narender, T. Khaliq, Shweta, Nishi, N. Goyal, and S. Gupta, “Synthesis of chromenochalcones and evaluation of their in vitro antileishmanial activity,” Bioorganic & Medicinal Chemistry, vol. 13, no. 23, pp. 6543–6550, 2005.
[26]
M. L. Go, M. Liu, P. Wilairat, P. J. Rosenthal, K. J. Saliba, and K. Kirk, “Antiplasmodial chalcones inhibit sorbitol-induced hemolysis of Plasmodium falciparum-infected erythrocytes,” Antimicrobial Agents and Chemotherapy, vol. 48, no. 9, pp. 3241–3245, 2004.
[27]
N. Yadav, S. K. Dixit, A. Bhattachary, et al., “Antimalarial activity of newly synthesized chalcone derivatives,” Chemical Biology & Drug Design, vol. 80, no. 2, pp. 340–347, 2012.
[28]
B. R. Shenai, P. S. Sijwali, A. Singh, and P. J. Rosenthal, “Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum,” Journal of Biological Chemistry, vol. 275, no. 37, pp. 29000–29010, 2000.
