New Cytotoxic Cyclobutanoid Amides, a New Furanoid Lignan and Anti-Platelet Aggregation Constituents from Piper arborescens

Abstract

Three new cyclobutanoid amides with trans-trans-trans configurations, piperarborenine C, piperarborenine D and piperarborenine E, and a new furanoid lignan, (+)-arborone, together with twelve known compounds, were isolated from the stems of Piper arborescens. The structures of these new compounds were determined by means of spectral analyses. Piperarborenine C, (+)-diayangambin, piplartine, piperolactam B, piperolactam C, aristolactam BIII, goniothalactam, and methyl trans-3,4,5-trimethoxycinnamate possessed anti-platelet aggregation activity in vitro. Among them, piplartine showed the most potent anti-platelet aggregation activity induced by collagen and showed an IC₅₀ value of 21.5 μM. Piperarborenines A - E, piperarborenine, aristololactam BIII and goniothalactam showed significant cytotoxic activity (IC₅₀ values < 4 μg/mL) against P-388, HT-29 and A549 cell lines in vitro.

Piper arborescens - Piperaceae - stem - cyclobutanoid amides - piperarborenine - furanoid lignan - (+)-arborone - anti-platelet aggregation activity - cytotoxicity

References

• 1 Lin T T, Lu S Y. Piperaceae in Flora of Taiwan; 2nd edition. Vol. 2 Editorial Committee of the Flora of Taiwan Taipei, Taiwan; 1996: pp 624-31
• 2 Shih M H, Ph.D. Thesis. National Tsing Hua University Hsinchu, Taiwan; 1991: p 10
• 3 Duh C Y, Wu Y C, Wang S K. Cytotoxic pyridone alkaloids from Piper arborescens .  Phytochemistry. 1990;  29 2689-91
• 4 Duh C Y, Wu Y C, Wang S K. Cytotoxic pyridone alkaloids from the leaves of Piper arborescens .  J Nat Prod. 1990;  53 1575-7
• 5 Lee F P, Chen Y C, Chen J J, Tsai I L, Chen I S. Cyclobutanoid amides from Piper arborescens .  Helv Chim Acta. 2004;  87 463-8
• 6 Teng C M, Chen W Y, Ko W C, Ouyang C. Antiplatelet effect of butylidenephthalide.  Biochim Biophys Acta. 1987;  924 375-82
• 7 O’Brien J R. Platelet aggregation II. Some results from a new method of study.  J Clin Path. 1962;  15 452-5
• 8 Tsai I L, Lin W Y, Teng C M, Ishikawa T, Doong S L, Huang M W, Chen Y C, Chen I S. Coumarins and antiplatelet constituents from the root bark of Zanthoxylum schinifolium .  Planta Med. 2000;  66 618-23
• 9 Montaudo G, Caccamese S. Structure and conformation of chalcone photodimers and related compounds.  J Org Chem. 1973;  38 710-6
• 10 Barnerji A, Sarkar M, Ghosal T, Pal S C, Shoolery J N. Sylvone, a new furanoid lignan of Piper sylvaticum .  Tetrahedron. 1984;  40 5047-52
• 11 Chen I S, Chen J J, Duh C Y, Tsai I L. Cytotoxic lignans from Formosan Hernandia nymphaeifolia .  Phytochemistry. 1997;  45 991-6
• 12 MacRae W D, Neil Towers G H. Non-alkaloidal constituents of Virola elongata bark.  Phytochemistry. 1985;  24 561-6
• 13 Joshi B S, Kamat V N, Saksena A K. On the structure of piplartine and a synthesis of dihydropiplartine.  Tetrahedron Lett. 1968;  20 2395-400
• 14 Desai S J, Prabhu B R, Mulchandani N B. Aristolactams and 4,5-dioxoaporphines from Piper longum .  Phytochemistry. 1988;  27 1511-5
• 15 Mahmood K, Chan K C, Park M H, Han Y N, Han B H. An aporphinoid alkaloid from Pseuduvaria macrophylla .  Phytochemistry. 1986;  25 1509-10
• 16 Olsen C E, Tyagi O D, Boll P M, Hussaini F A, Parmar V S, Sharma N K, Taneja P, Jain S C. An aristolactam from Piper acutisleginum and revision of the structures of piperolactam B and D.  Phytochemistry. 1993;  33 518-20
• 17 Lo W L, Chang F R, Wu Y C. Alkaloids from the leaves of Fissistigma glaucescens .  J Chin Chem Soc. 2000;  47 1251-6
• 18 Cao S G, Wu X H, Sim K Y, Tan B KH, Pereira J T, Goh S H. Styryl-lactone derivatives and alkaloids from Goniothalamus borneensis (Annonaceae).  Tetrahedron. 1998;  54 2143-8
• 19 Dutta C P, Banerjee N, Sil A K, Roy D N. Studies on the genus Piper: studies on the roots of Piper longum Linn.  Indian J Chem Sec B. 1977;  15 583-4
• 20 Chia Y C, Chang F R, Teng C M, Wu Y C. Aristolactam and dioxoaporphines from Fissistigma balansae and Fissistigma oldhamii .  J Nat Prod. 2000;  63 1160-3