Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (II): apoptosis of antiproliferactive principle (24,25-dihydrowithanolide D) against ATL cell lines and structure–activity relationships with withanolides isolated from solanaceous plants

Journal of Natural Medicines - Tập 67 - Trang 415-420 - 2012
Daisuke Nakano1, Kenji Ishitsuka2, Hiroo Katsuya2, Naoko Kunami2, Rumiko Nogami2, Yuka Yoshimura2, Michika Matsuda1, Mio Kamikawa1, Ryota Tsuchihashi1, Masafumi Okawa1, Tsuyoshi Ikeda3, Toshihiro Nohara3, Kazuo Tamura2, Junei Kinjo1
1Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
2Department of Internal Medicine, Division of Medical Oncology, Hematology and Infectious Disease, Fukuoka University, Fukuoka, Japan
3Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan

Tóm tắt

Adult T-cell leukemia/lymphoma (ATL) is an incurable peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I. In our preceding paper, 214 extracts from 162 plants were screened to elucidate the antiproliferative principles against ATL cell lines. Several withanolides were isolated and the structure–activity relationships (SAR) examined. To extend the search for SAR, 31 further withanolides, previously isolated from solanaceous plants, were tested against ATL cell lines. The presence of a 4β-hydroxy group as well as a 5β,6β-epoxy group appeared to be essential for the activity. In contrast, the presence of a sugar moiety at either the 3- or the 27-position led to a reduction in the activity. Furthermore, 24,25-dihydrowithanolide D (13) was identified as the most potent inhibitor, showing selective toxicity against ATL cell lines by inducing apoptotic cell death.

Tài liệu tham khảo

Ishitsuka K, Tamura K (2008) Treatment of adult T-cell leukemia/lymphoma: past, present, and future. Eur J Haematol 80:185–196 Nakano D, Ishitsuka K, Hatsuse T, Tsuchihashi R, Okawa M, Okabe H, Tamura K, Kinjyo J (2011) Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles structure–activity relationships with withanolides. J Nat Med 65:559–567 Matsuda H, Murakami T, Kishi A, Yoshikawa M (2001) Structures of withanosides I, II, III, IV, V, VI, and VII, new withanolide glycosides, from the roots of Indian Withania somnifera Dunal and inhibitory activity for tachyphylaxis to clonidine in isolated guinea-pig ileum. Bioorg Med Chem 9:1499–1507 Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K (2002) Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull 50:760–765 Shingu K, Yahara S, Nohara T, Okabe H (1992) Three new withanolides, Physagulins A, B and D from Physalis angulata L. Chem Pharm Bull 40:2088–2091 Jayaprakasam B, Strasburg GA, Nair MG (2004) Potent lipid peroxidation inhibitors from Withania somnifera fruits. Tetrahedron 60:3109–3121 Zhang H, Samadi AK, Gallagher RJ, Araya JJ, Tong X, Day VW, Cohen MS, Kindscher K, Gollapudi R, Timmermann BN (2011) Cytotoxic withanolide constituents of Physalis longifolia. J Nat Prod 74:2532–2544 Anjaneyulu ASR, Rao DS (1997) A new withanolide from leaves of Withania somnidera. Ind J Chem Sect B 36:161–165 Kirson I, Glotter E, Abraham A, Lavie D (1970) Constituents of Withania somnifera Dun. XI. The structure of three new withanolides. Tetrahedron 26:2209–2219 Shingu K, Miyagawa M, Yahara S, Nahara T (1993) Physapruins A and B, two new withanolides from Physalis pruinosa Bailey. Chem Pharm Bull 41:1873–1875 Glotter E, Abraham A, Gunzberg G, Kirson I (1977) Naturally occurring steroidal lactones with a 17a-oriented side chain. Structure of withanolide E and related compounds. J Chem Soc Perkin Trans I 4:341–346 Shingu K, Yahara S, Okabe H, Nahara T (1992) Three new withanolides, Physagulins E, F and G from Physalis angulata L. Chem Pharm Bull 40:2448–2451 Nagafuji S, Okabe H, Akahane H, Abe F (2004) Trypanocidal constituents in plants 4. Withanolides from the aerial parts of Physalis angulata. Biol Pharm Bull 27:193–197 Abe F, Nagafuji S, Okawa M, Kinjo J (2006) Trypanocidal constituents in plants 6. Minor withanolides from the aerial parts of Physalis angulata. Chem Pharm Bull 54:1226–1228 Shingu K, Yahara S, Nohara T (1994) Constituents of Solanaceous plants 28. Five new ergostane-related compounds from Nicandra physaloides. Chem Pham Bull 42:318–321 Shingu K, Fujii H, Mizuki K, Ueda I, Yahara S, Nohara T (1994) Ergostane glycosides from Petunia hybrida. Phytochemistry 36:1307–1314 Zhu XH, Takagi M, Ikeda T, Midzuki K, Nohara T (2001) Withanolide-type steroids from Solanum cilistum. Phytochemistry 56:741–745 Zhu XH, Ando J, Takagi M, Ikeda T, Yoshimitsu A, Nohara T (2001) Four novel withanolide-type steroids from the leaves of Solanum cilistum. Chem Pharm Bull 49:1440–1443 Miyoshi I, Kubonishi I, Sumida M, Hiraki S, Tsubota T, Kimura I, Miyamoto K, Sato J (1980) A novel T-cell line derived from adult T-cell leukemia. Gann 71:155–156 Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, Nagata K, Hinuma Y (1981) Type C virus particles in a cord T-cell line derived by cocultivating normal human cord leukocytes and human leukaemic T cells. Nature 294:770–771