Planta Med 2004; 70(1): 70-72
DOI: 10.1055/s-2004-815460
Letter
© Georg Thieme Verlag Stuttgart · New York

In vitro Antiprotozoal and Cytotoxic Activities of Some Alkaloids, Quinones, Flavonoids, and Coumarins

Maria del Rayo Camacho1 , 4 , J. David Phillipson1 , Simon L. Croft2 , Vanesa Yardley2 , Pablo N. Solis3
  • 1Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, London, UK
  • 2Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
  • 3CIFLORPAN, Facultad de Farmacia, Universidad de Panama, Panama
  • 4Facultad de Ciencias Químicas, Universidad Autonoma de Nuevo Leon, México
M. D. R. Camacho is grateful for the research fellowship awarded by CONACYT-Mexico to carry out PhD studies in the University of London. S. L. Croft received financial support from the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR).
Further Information

Publication History

Received: June 2, 2003

Accepted: October 18, 2003

Publication Date:
06 February 2004 (online)

There is a need for antiprotozoal drugs with novel structures and modes of action [1] and over several years extracts from plant species have been tested for antiprotozoal activities in our laboratories [2]. Not all of the compounds isolated during this research were tested against a full range of protozoal organisms or assessed for their cytotoxicity to mammalian cells. In this communication the in vitro activities of 26 isolated compounds not previously fully assessed for activity against species of Plasmodium, Leishmania and Trypanosoma are reported and compared with cytotoxicity to KB cells.

The compounds tested represent four different groups of natural products, alkaloids, quinones, flavonoids and coumarins. The quinones picramnosides A - C were isolated from Picramnia antidesma (DC) W. Thomas [3] and benzo[g]isoquinoline-5,10-dione and 1-hydroxybenzoisochromanquinone from Cephaelis camponutans Dwyer and Hayden [4]. These species were investigated because other species of these two genera contain either quassinoids or alkaloids with antiprotozoal activities. A series of indole alkaloids including strictosidine, strictosidine lactam and vallesiachotamine was obtained from Cephaelis dichroea (Standley) Standley [5]. Teloxys graveolens (Willd.) Weber and Hintonia latiflora (Sesse et Mocino ex DC) Bullock are used in Mexican traditional medicine for the treatment of fevers [6], [7]. The flavonoids pinostrobin, pinocembrin and chrysin were isolated from T. graveolens [7] and 7-methylluteolin with 3 coumarins from H. latiflora [8].

The in vitro antiprotozoal activities of the 26 compounds are summarised in Tables [1] and 2. Eight compounds have IC50 values equal to, or less than, 10 μM. The quinone 1-acetyl-benzoisochromanquinone was the most active against L. donovani promastigotes, amastigotes, T. cruzi, and T. b. brucei with IC50 values of 2.32, 1.98, 6.60, and 0.65 μM, respectively (Table [1]). This quinone was 18 times more potent (IC50 = 0.54 μg/mL) than the standard drug pentostam (IC50 = 9.75 μg/mL) against L. donovani amastigotes. The quinone benzo[g]isoquinoline-5,10-dione had an IC50 value of 4.02 μM against P. falciparum in vitro and 1-hydroxybenzoisochromanquinone an IC50 value of 3.3 μM against T. b. brucei trypomastigotes (Table [1]). The other compounds tested showed only weak activity in comparison with the standard antiprotozoal drugs. None of the compounds tested showed significant cytotoxic effects against KB cells in comparison with the standard podophyllotoxin (IC50 = 0.015 μM). In assessing selectivity of antiprotozoal action, it was observed that 1-acetylbenzoisochromanquinone, strictosidine, and pinocembrine, exhibited higher activity towards T. b. brucei than to other parasites and mammalian cells, indicating some degree of selectivity. In contrast, the antiprotozoal activity of benzo[g]isoquinoline-5,10-dione may be attributed to its cytotoxic effects. This is the first report of the antileishmanial and antitrypanosomal activity of the tested compounds and with the exception of the benzoquinones, the antiplasmodial activities of the compounds are reported for the first time for the tested compounds.

Table 1 Antiprotozoal and cytotoxic activities of alkaloids, quinones and flavonoids Samples L. donovani promastigotes L. donovani amastigotes T. cruzi amastigotes T. b. brucei bloodstream form trypomastigotes P. falciparum K1 KB cells IC50 [μM] Alkaloids Strictosidine 14.34 ± 1.75 39.30 ± 1.04 27.53 ± 1.00 6.14 ±  0.70 150.70 ±  1.17 73.86 ±  1.03 Acetylstrictosidine 6.25 ± 0.98 2.14 ± 0.60 > 90 16.72 ±  1.10 ND 130.66 ±  1.15 Strictosidine lactam >100.40 > 90 > 90 30 ±  1.67 546.73 ±  1.95 641.20 ±  1.27 Acetylstrictosidine lactam 84.43 ± 0.75 40.93 ± 1.55 ND 29.80 ±  2.30 141.43 ±  1.46 322.49 ±  2.79 Vallesiachotamine 181.51 ± 2.75 > 90 ND ND ND 974.11 ±  3.70 Quinones Benzo[g]isoquinoline-5,10-dione 6.60 ± 0.28 16.51 ± 0.07 (T) T 7.51 ±  0.14 4.02 ±  1.6 7.75 ±  1.19 1-Hydroxybenzoisochromanquinone 37.65 ± 1.13 14.09 ± 0.12 (T) 8.13 ±  1.23 (T) 3.303 ±  0.09 11.56 ±  1.1 8.09 ±  0.22 1-Acetylbenzoisochromanquinone 2.32 ± 0.08 1.98 ± 0.04 6.60 ±  0.22 0.65 ±  0.007 22.12 ±  3.8 11.80 ±  2.18 Picramnioside A 50.59 ± 0.40 > 90 > 90 > 30 75.45 ±  2.14 70.27 ±  1.87 Picramnioside B 46.52 ± 1.20 > 90 > 90 > 30 > 1 121.08 19.60 ±  0.86 Picramnioside C 145.74 ± 2.10 > 90 > 90 > 30 > 1 121.08 18.65 ± 2.03 Flavonoids Pinostrobin 550.34 ± 1.0 > 90 ND > 30 ND >1 851.85 Pinocembrin 190.40 ± 1.21 > 90 ND 10.47 ±  1.30 154.902 ± 4.12 123.51 ±  1.11 Acetylpinocembrin 390.10 ± 2.52 > 90 ND > 30 ND 111.12 ± 1.70 Chrysin 207.11 ± 1.22 > 90 ND 13.50 ±  1.06 194.76 ±  2.88 1109.88 ±  3.78 7-Methylluteolin 35.70 ± 1.18 T ND 13.33 ±  1.01 46.33 ±  2.68 37.83 ±  2.00 Standards Pentamidine 0.40 ± 0.09 ND ND 3.4 × 10-4 ± 5 × 10-5 ND ND Pentostam ND 9.75a ± 1.13 ND ND ND ND Nifurtimox ND ND 2.90 ± 0.1 ND ND ND Chloroquine ND ND ND ND 0.59 ± 0.10 ND Podophyllotoxin ND ND ND ND ND 0.015 ± 0.008 ND: Not determined. T: toxic. a μg/mL.

Table 2 Antiprotozoal and cytotoxic activities of coumarins Samples L. donovani promastigotes  L donovani amastigotes T. b. brucei bloodstream trypomastigotes P. falciparum K1 KB cells IC50 [μM] Coumarins 5-O-[β-D-Galactopyranosyl]-3′,4′-dihydroxy-7-methoxy-4-phenylcoumarin 42.98 ± 3.56 > 90 > 30 378.74 ±  1.67 720.04 ± 1.89 5-O-[β-D-Glucopyranosyl]-3′,4′-dihydroxy-7-methoxy-4-phenylcoumarin 28.85 ±  1.24 > 90 > 30 197.40 ±  2.78 >1 082.25 ±  4.56 5-O-[β-D-Tetraacetoxygalactopyranosyl]-3′,4′-diacetoxy-7-methoxy-4-phenylcoumarin 50.85 ±  1.58 > 90 > 30 133.75 ±  1.67 108.02 ±  2.57 5-O-[β-D-Tetraacetoxyglucopyranosyl]-3′,4′-diacetoxy-7-methoxy-4-phenylcoumarin 12.39 ± 1.11 > 90 10.73 ±  1.31 121.29 ±  1.34 173.89 ±  3.20 5-O-[β-D-Galactopyranosyl]-7,3′,4′-trimethoxy-4-phenylcoumarin >1 020.40 > 90 > 30 ND 394.26 ±  1.45 5-O-[β-D-Glucopyranosyl]-7,3′,4′-trimethoxy-4-phenylcoumarin 10.20 ±  0.85 > 90 > 30 ND 436.31 ±  3.30 5,3′,4′-Trihydroxy-7-methoxy-4-phenylcoumarin 30.00 ±  0.67 T 30 280.47 ±  2.59 252.87 ±  2.20 5,3′,4′-Triacetoxy-7-methoxy-4-phenylcoumarin 1123.54 ± 2.44 > 90 > 30 60.33 ±  2.21 211.06 ±  1.19 5-O-[β-D-Tetraacetoxygalactopyranosyl]-4′-acetyl-7-methoxy-4-phenylcoumarin 131.81 ±  3.56 > 90 10.65 ±  1.15 137.96 ± 2.30 188.27 ±  3.10 4′,5′-Dihydroxy-7-methoxy-4-phenyl-5,2′-oxidocoumarin 143.56 ±  3.55 > 90 > 30 473.99 ±  1.49 115.60 ±  1.33 Standards Pentamidine 0.40 ± 0.09 ND 3.4 × 10-4 ± 5 × 10-5 ND ND Pentostam ND 9.75a ± 1.13 ND ND ND Chloroquine ND ND ND 0.59 ± 0.10 ND Podophyllotoxin ND ND ND ND 0.015 ± 0.008 ND: not determined. T: toxic. a μg/mL.

References

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Dr. Maria del Rayo Camacho Corona

Universidad Autonoma de Nuevo Leon

Facultad de Ciencias Químicas

Jefatura de QFB (Edificio de la dona 2º. Piso)

Ciudad Universitaria

C.P. 66400

San Nicolas de los Garza

Nuevo Leon

Mexico

Email: mrayocamacho@yahoo.com.mx