Cucullamide, a New Putrescine Bisamide from Amoora cucullata

Abstract

Amoora cucullata (Meliaceae) is a tall tree, grown in the coastal areas of Southeast Asia and the Indian Ocean. This plant has been used as a folk medicine for treatment of inflammation, marrow and diarrhea.1) Additionally, juice of the leaves has antibacterial activity and extensively used for the treatment of dysentery, skin and cardiac diseases.2) The crude methanolic extracts of leaves were reported to show antiinflammatory, antinociceptive, diuretic, and central nervous system (CNS) depressant activities.3,4) Phytochemical analysis of the stem bark of Amoora cucullata led to the isolation of fridelin, stigmasterol, b-sitosterol, betulinic acid and caffeic acid.5) Furthermore, analysis of the leaves showed the presence of several polyphenols and tannins, whether from its fruits, several rocagloic acid derivatives were isolated.6) In continuation of our phytochemical screening of A. cucullata leaves, we report the isolation and structure elucidation of one new putrescine bisamide, cucullamide (1), along with five known natural compounds (2-6) ( Fig. 1). The new putrescine bisamide derivative (1) and dasyclamide (2) were evaluated for their Wnt signal inhibitory activities, since we are recently interested in screening studies targeting signaling molecules related to cancer diseases. 7) Results and DiscussionThe fresh leaves of Amoora cucullata were collected from the Sundarbans Mangrove Forests, Bangladesh.8) The methanolic extract of A. cucullata was partitioned successively with ethyl acetate, nBuOH, and water. The ethyl acetate fraction was then subjected to repeated column chromatography on Sephadex LH20, silica gel 60N, octadecylsilyl (ODS) gel, and preparative thin layer chromatography (PTLC) to obtain dasyclamide (2), 9) ent-2b-hydroxymanool (3), 10) chrysin (4), 11) apigenin (5), 12) and kaempferol-3-O-b-D-glucopyranoside (6). 13) All of the known compounds were identified by spectroscopic data including 1D and 2D NMR and by comparison with those published in the literature. All these five known compounds are isolated and reported for the first time from this plant.Compound 1 was isolated as a white solid. On the TLC plate after developing compound 1, it gave a positive color reaction after spraying with Dragendorff reagent and dark fluorescence under UV light at 254 nm. The electrospray ion- Sciences, Chiba University; 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan: b Pharmacy Discipline, Life Science School, Khulna University; Khulua-9208, Bangladesh: and c Chemistry Department, Faculty of Science, Helwan University; Cairo 11795, Egypt. Received April 30, 2010; accepted May 21, 2010; published online May 21, 2010 A new putrescine bisamide derivative named cucullamide (1) was isolated from the leaves of Amoora cucullata, together with five known natural products, dasyclamide (2), ent-2b-hydroxymanool (3), chrysin (4), apigenin (5), and kaempferol-3-O-b-D-glucopyranoside (6). The structure of the new isolated compound was elucidated on the basis of 1D and 2D NMR as well as high resolution-ele...

Biology-Orientated Synthesis of Putrescine Bisamides Gigantamide A, Dasyclamide, and Cucullamide

“…Naturally occurring bioactive putrescine bisamides 5,6 Syntheses of these linear target compounds demand appropriate stepwise dehydrative coupling reactions of three/four essential building blocks. Maleimides obtained from the putrescine-type diamine are prone to further intramolecular dehydrative cyclizations.…”

“…[1][2][3][4][5][6][7] They exhibit a broad range of biological activity, such as antileukemic, antiviral, antifungal, anti-inflammatory, antinociceptive, diuretic, CNS depressant, and insecticidal activity. [1][2][3][5][6][7] Moreover putrescine diamides are the potential biogenetic precursors of rocaglamides that possess strong insecticidal activity comparable to azadirachtin. 8 They also display pronounced antiproliferative activity against human cancer cells.…”

“…9 Recently the putrescinebased natural products (±)-gigantamide A, dasyclamide, and grandiamide D were isolated from Aglaia gigantea 5 and very recently dasyclamide and cucullamide were isolated from Amoora cucullata (Figure 1). 6 Dasyclamide, earlier known as aglairubine, was previously isolated from several Aglaia species viz., A. rubiginosa, A. australiensis, A. spectabilis, A. meridionalis, A. roburghiana, and A. dasyclada. 1,[3][4][5][6] Its initial structural assignment was revised and re-established on the basis of extensive NMR studies and finally confirmed by using X-ray crystallographic data.…”

“…6 Dasyclamide, earlier known as aglairubine, was previously isolated from several Aglaia species viz., A. rubiginosa, A. australiensis, A. spectabilis, A. meridionalis, A. roburghiana, and A. dasyclada. 1,[3][4][5][6] Its initial structural assignment was revised and re-established on the basis of extensive NMR studies and finally confirmed by using X-ray crystallographic data. 1,4,5 To date, syntheses of these imperative bioactive natural products have not been reported in the literature.…”

Synthesis of Putrescine Bisamides as Antimicrobial and Anti-Inflammatory Agents

“…Putrescine bisamides are one of the subclasses of naturally occurring polyamides [1]. During the last two decades several symmetrical and unsymmetrical putrescine bisamides have been isolated from Aglaia [2][3][4], Liberica [5], and Carydalis [6], species. These compounds have been reported to possess various biological activities including cytotoxicity [7], anti-inflammatory [8], antioxidant [9,10], insecticidal [11,12], and antiviral activity.…”