Two New Peltogynoids from Acacia nilotica Delile with Kinase Inhibitory Activity

Abstract

Two new peltogynoids, acanilol A (1) and acanilol B (2), were isolated from the stem bark of Acacia nilotica (L.) Delile, together with the known triterpene lupenone. The structures of the new compounds were established on the basis of their spectral data, mainly UV, NMR, and mass spectrometry. The new compounds were tested as kinase inhibitors against CDK1, GSK3, CK1, and DYRK1A, and acanilol B was identified as a DYRK1A inhibitor, with an IC₅₀ of 19 µM.

Key words

Acacia nilotica - Leguminosae - peltogynoids - acanilol A - acanilol B - DYRK

References

• 1 Pedley L. Derivation and dispersal of Acacia (Leguminosae), with particular reference to Australia, and the recognition of Senegalia and Racosperma.  Bot J Linn Soc. 1986;  92 219-254
• 2 Seigler D S. Phytochemistry of Acacia – sensu lato.  Biochem Syst Ecol. 2003;  31 845-873
• 3 Abd El Nabi O M, Reisinger E C, Reinthaler F F, Still F, Eibel U, Krejs G J. Antimicrobial activity of Acacia nilotica (L.) Willd. Ex Del. Var nilotica (Mimosaceae).  J Ethnopharmacol. 1992;  37 77-79
• 4 Elizabeth K M, Sireesha D, Rao K N, Rao M V B. Antimicrobial activity of Acacia nilotica.  Asian J Chem. 2005;  18 191-195
• 5 Mustafa N K, Tanira M O M, Dar F K, Nsanze H. Antimicrobial activity of Acacia nilotica subsp. nilotica fruit extracts.  Pharm Pharmacol Commun. 1999;  5 583-586
• 6 Bhargava A, Srivastava A, Kumbhare V. Antifungal activity of polyphenolic complex of Acacia nilotica bark.  Indian Forester. 1998;  124 292-298
• 7 Chaubal R, Mujumdar A M, Misar A, Deshpande N R. Isolation of phenolic compounds from Acacia nilotica with topical antiinflammatory activity.  Asian J Chem. 2005;  17 1595-1599
• 8 Chaubal R, Mujumdar A M, Puranik V G, Deshpande V H, Deshpande N R. Isolation and X-ray study of an anti-inflammatory active androstene steroid from Acacia nilotica.  Planta Med. 2003;  69 287-288
• 9 Khalid S A, Yagi S M, Khritova P, Duddeck H. (+)-Catechin-5-galloyl ester as a novel natural polyphenol from the bark of Acacia nilotica of Sudanese origin.  Planta Med. 1989;  55 556-558
• 10 Malan E. Derivatives of (+)-catechin-5-gallate from the bark of Acacia nilotica.  Phytochemistry. 1991;  30 2737-2739
• 11 Chauhan D, Singh J, Siddiqui I R. Isolation of two flavonol glycosides from the seeds of Acacia nilotica.  Indian J Chem. 2000;  39 , [B]: 719–722
  
• 12 Prakash L, Garg G. Chemical constituents of the roots of Millingtonia hortensis L. and Acacia nilotica (L.) Del.  J Indian Chem Soc. 1981;  58 96-97
• 13 Chalk R C, Stoddart J F, Szarek W A, Jones J K N. Isolation of two arabinobioses from Acacia nilotica gum.  Can J Chem. 1968;  46 2311-2313
• 14 Waiss Jr A C, Lundin R E, Lee A, Corse J. Photochemistry of quercetin pentamethyl ether.  J Am Chem Soc. 1967;  89 6213-6218
• 15 Drewes S E, Roux D G. Isolation of mopanin from Colophospermum mopane and interrelation of flavonoid components of Peltogyne spp.  J Chem Soc C. 1967;  1407-1410
• 16 Brandt E V, Ferreira D, Roux D G. Metabolites from the purple heartwood of Mimosoideae. Part 2. Acacia carnei maiden: isolation, synthesis, and reactions of crombeone.  J Chem Soc [Perkin I]. 1981;  514-521
• 17 McPherson D D, Cordell G A, Soejarto D D, Pezzuto J M, Fong H H S. Peltogynoids and homoisoflavonoids from Caesalpinia pulcherrima.  Phytochemistry. 1983;  22 2835-2838
• 18 Choudhary M I, Nur-e-Alam M, Akhtar F, Ahmad S, Baig I, Öndögnii P, Gombosurengyin P, Atta-ur-Rhaman. Five new peltogynoids from underground parts of Iris bungei: a Mongolian medicinal plant.  Chem Pharm Bull. 2001;  49 1295-1298
• 19 Lu H, Chang D J, Baratte B, Meijer L, Schulze-Gahmen U. Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin.  J Med Chem. 2005;  48 737-743
• 20 Holder S, Zemskova M, Zhang C, Tabrizizad M, Bremer R, Neidigh J W, Lilly M B. Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase.  Mol Cancer Ther. 2007;  6 163-172
• 21 Puapairoj P, Naengchomnong W, Kijjoa A, Pinto M M, Pedro M, Nascimento M S J, Silva A M S, Herz W. Cytotoxic activity of lupane-type triterpenes from Glochidion sphaerogynum and Glochidion eriocarpum two of which induce apoptosis.  Planta Med. 2005;  71 208-213
• 22 Glide, version 3.4. New York; Schrödinger, LLC 2004
• 23 Echalier A, Bettayeb K, Ferandin Y, Lozach O, Clement M, Valette A, Liger F, Marquet B, Morris J C, Endicott J A, Joseph B, Meijer L. Meriolins [3-(Pyrimidin-4-yl)-7-azaindoles]: synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex.  J Med Chem. 2008;  51 737-751