Cytotoxic and Antimicrobial Activities of Aporphine Alkaloids Isolated from Stephania venosa (Blume) Spreng

Abstract

The cytotoxic activity of five alkaloids, namely 4,5-dioxo-dehydrocrebanine (1), dehydrocrebanine (2), crebanine (3), oxostephanine (4), and thailandine (5) isolated from the tuber and leaves of Stephania venosa (Blume) Spreng was investigated. Thailandine showed the strongest activity against lung carcinoma cells (A549) (IC₅₀ of 0.30 µg/mL) with very low cytotoxicity against normal embryonic lung cells (MRC-5). Thailandine also demonstrated strong activity against Plasmodium falciparum, K1 strain (IC₅₀ of 20 ng/mL), and Mycobacterium tuberculosis H₃₇Ra (MIC of 6.25 µg/mL) as well as gram-positive bacteria such as Streptococcus pneumoniae and Staphylococcus aureus. Oxostephanine exhibited strong activity against breast cancer (BC) and acute lymphoblastic leukemia cells (MOLT-3) with an IC₅₀ of 0.24 and 0.71 µg/mL, respectively, and exhibited very low cytotoxicity against MRC-5 cells. Dehydrocrebanine demonstrated strong activity against promyelocytic leukemia cells (HL-60) with an IC₅₀ of 2.14 µg/mL whereas crebanine showed weak activity against cancer cell lines. However, both of them showed cytotoxicity against MRC-5 cells.

Key words

Stephania venosa (Blume) Spreng - Menispermaceae - thailandine - cytotoxicity - antimicrobial - antimalarial - antifungal

References

• 1 Thornber C W. Alkaloids of the Menispermaceae.  Phytochemistry. 1970;  9 157-187
• 2 Schiff P L. Bisbenzylisoquinoline alkaloids.  J Nat Prod. 1987;  50 529-599
• 3 Chen Y, Fang S, Liang D, Jiang F. Alkaloids of Stephania yunnanensis.  Zhiwu Xuebao. 1989;  31 296-299
• 4 Kozuka M, Miyaji K, Sawada T, Tomita M. Major alkaloids of the leaves and stems of Stephania rotunda.  J Nat Prod. 1985;  48 341
• 5 Nadkarni A K. Indian materia medica. Bombay; Popular Book Depot 1954: 167
• 6 Anon. The wealth of India-raw material. New Delhi; CSIR 1976
• 7 Patra A. Promorphinane and hasubanane alkaloids of Stephania suberosa.  Phytochemistry. 1987;  26 2391-2395
• 8 Patra A, Montgometry C T, Freyer A J, Guinaudeau H, Shamma M, Tantisewie B, Pharadai K. The protoberberine alkaloids of Stephania suberosa.  Phytochemisty. 1987;  26 547-549
• 9 Watt J M, Breyer-Brandwijk M G. The medicinal and poisonous plants of southern and eastern Africa. London; Livingstone 1962: 458
• 10 Bun S S, Larget M, Chea A, Bun H, Ollivier E, Elias R. Cytotoxic activity of alkaloids isolated from Stephania rotunda.  Phytother Res. 2009;  23 587-590
• 11 Deng Y, Li J, Gao C, Yang L. Inhibitory activity of the extract from the root tubers of Stephania kwangsiensis and its compounds against pathogenic fungi and bacteria.  Zhiwu Baohu. 2006;  32 43-46
• 12 Chea A, Hout S, Bun S S, Tabatadze N, Gasquet M, Azas N, Elias R, Balansard G. Antimalarial activity of alkaloids isolated from Stephania rotunda.  J Ethnopharmacol. 2007;  112 132-137
• 13 Ingkaninan K, Phengpa P, Yuenyongsawad S, Khorana N. Acetylcholinesterase inhibitors from Stephania venosa tuber.  J Pharm Pharmacol. 2006;  58 695-700
• 14 Chen C F, Chou Z, Shen Y C. Anti-inflammatory agent containing defined Radix Stephania tetrandrae extracts. Jpn Kokai Tokkyo Koho. JP Patent 2004067694 2004
• 15 Tsutsumi T, Kobayashi S, Shinjiro L, Yuan Y, Kontani H. Anti-hyperglycemic effect of fangchinoline isolated from Stephania tetradra Radix in streptozotocin-diabetic mice.  Biol Pharm Bull. 2003;  26 313-317
• 16 Ma C M, Nakamura N, Miyashiro H, Hattori M, Komatsu K, Kawahata T, Otake T. Screening of Chinese and Mongolian herbal drugs for anti-human immunodeficiency virus type 1(HIV-1) activity.  Phytother Res. 2002;  16 186-189
• 17 Ohsaki M, Kurokawa M, Nawawi A, Nakamura N, Hattori M, Shiraki K. Characterization of anti-herpes simplex virus type 1 activity of an alkaloid FK 3000 from Stephania cepharantha.  Wakan Iyakugaku Zasshi. 2002;  19 129-136
• 18 Del R C, Maria K, Geoffrey C, Warhurst D C, Croft S L, Phillipson J D. Oxoaporphine alkaloids and quinines from Stephania dinklagai and evaluation of their antiprotozoal activities.  Planta Med. 2000;  66 478-480
• 19 Newman D J, Cragg G M, Snader K M. Natural products as sources of new drugs over the period 1981–2002.  J Nat Prod. 2003;  66 1022-1037
• 20 Watanabe Y, Matsui M, Iibuchi M, Hiroe S. Two oxoaporphine alkaloids of Stephania japonica.  Phytochemistry. 1975;  14 2522-2523
• 21 Kunitomo J I, Murakami Y, Oshikata M, Shingu T, Akasu M, Lu S T, Chen I S. The alkaloids of Stephania sasakii: structure of five new alkaloids.  Phytochemistry. 1990;  19 2735-2739
• 22 Guinaudeau H, Shamma M, Tantisewie B, Pharadai K. 4,5,6,6a-Tetrahydro-N-methyl-7-oxoaporphinium salts.  Chem Commun. 1981;  21 1118-1119
• 23 Blanchfield J T, Sands D P A, Kennard C H L, Byriel K A, Kitching W. Characterisation of alkaloids from some Australian Stephania (Menispermaceae) species.  Phytochemistry. 2003;  63 711-720
• 24 Likhitwitayawuid K, Dej-Adisai S, Jongbunprasert V, Krungkrai J. Antimalarials from Stephania vanosa, Prismatomeris sessiliflora, Diospyros montana, and Murraya siamensis.  Planta Med. 1999;  65 754-756
• 25 Montanha J, Amoros M, Boustie J, Girre L. Anti-herpes virus activity of aporphine alkaloids.  Planta Med. 1995;  61 419-424
• 26 Guinaudeau H, Shamma M, Tantisewie B, Pharadai K. 4,5,6,6a-Tetrahydro-N-methyl-7-oxoaporphinium salts.  J Chem Soc Chem Commun. 1981;  21 1118-1119
• 27 Wirasathien L, Boonarkart C, Pengsuparp T, Suttisri R. Biological activities of alkaloids from Pseuduvaria setosa.  Pharm Biol. 2006;  44 274-278
• 28 Likhitwitayawuid K, Angerhofer C K, Chai H, Pezzuto J M, Cordell G A. Cytotoxic and antimalarial alkaloids from the tubers of Stephania pierrei.  J Nat Prod. 1993;  56 1468-1478
• 29 Nozaka T. Mutagenicity of isoquinoline alkaloids, especially of the aporphine type.  Mutat Res. 1990;  240 267-279
• 30 Mosman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 31 Carmichael J, Degraff W G, Gazdar A F, Minna J D, Mitchell J B. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing.  Cancer Res. 1987;  47 936-942
• 32 Doyly A, Griffiths J B. Mammalian cell culture-essential techniques. Chichester; Wiley & Sons 1997
• 33 Tominaga M H, Ishiyama M, Ohseto F, Sasamoto K, Hamamoto T, Suzuki K, Watanabe M. A water-soluble tetrazolium salt useful for colorimetric cell viability assay.  Anal Commun. 1999;  36 47-50
• 34 Fenner R, Sortino M, Kuze R S M, Dall A R, Ferraz A, Bernardi A P, Albring A, Nör C, von Poser G, Schapoval E, Zacchino S. Antifungal activity of some Brazilian Hypericum species.  Phytomedicine. 2005;  12 236-240
• 35 Navarro G V M, Gonzalez A, Fuentes M, Aviles M, Rios M Y, Zepeda G, Rojas M G. Antifungal activity of nine traditional Maxican medicinal plants.  J Ethnopharmacol. 2003;  87 85-88
• 36 Desjardins R E, Canfield C J, Haynes J D, Chulay J D. Quantitative assessment of antimalarial activity in vitro by a semi-automated microdilution technique.  Antimicrob Agents Chemother. 1979;  16 710-718
• 37 Lisa A C, Scott G. Microplate Alamar Blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.  Antimicrob Agents Chemother. 1997;  41 1004-1009
• 38 Skehan P, Ritsa S, Dominic S. New colorimetric cytotoxicity assay for anticancer-drug screening.  J Natl Cancer Inst. 1990;  82 1107-1112