Pentacyclic Ingamine Alkaloids, a New Antiplasmodial Pharmacophore from the Marine Sponge Petrosid Ng5 Sp5

Muhammad Ilias; Mohamed A. Ibrahim; Shabana I. Khan; Melissa R. Jacob; Babu L. Tekwani; Larry A. Walker; Vladimir Samoylenko

doi:10.1055/s-0032-1315213

Planta Medica, Inhaltsverzeichnis

Planta Med 2012; 78(15): 1690-1697
DOI: 10.1055/s-0032-1315213

Natural Product Chemistry

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Pentacyclic Ingamine Alkaloids, a New Antiplasmodial Pharmacophore from the Marine Sponge Petrosid Ng5 Sp5

Muhammad Ilias

¹National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA

,

Mohamed A. Ibrahim

¹National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA

²Department of Chemistry of Natural Compounds, Division of Pharmaceutical and Drug Industries Division, National Research Center, Dokki, Giza, Egypt

,

Shabana I. Khan

¹National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA

³Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Melissa R. Jacob

¹National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA

,

Babu L. Tekwani

¹National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA

⁴Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Larry A. Walker

¹National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA

⁴Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Vladimir Samoylenko

¹National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA

› Institutsangaben

Abstract

Two new pentacyclic ingamine alkaloids, namely 22(S)-hydroxyingamine A (2) and dihydroingenamine D (3), together with the known ingamine A (1), have been isolated from marine sponge Petrosid Ng5 Sp5 (family Petrosiidae) obtained from the open repository of the National Cancer Institute, USA. The structures of compounds 1–3 were determined using 1D and 2D NMR, and HRESIMS techniques. The absolute configuration of both the C9 and C22 of 2 was determined as (S) using a modified Mosher esterification method. Compounds 1 and 3 showed strong antiplasmodial activity against chloroquine-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum with IC₅₀ values of 90 and 78 ng/mL and 72 and 57 ng/mL, respectively, while 2 was found to be less active (IC₅₀ values of 200 and 140 ng/mL, respectively). Compounds 1–3 were found to be devoid of in vitro cytotoxicity against human solid tumor cells of breast (BT-549), ovary (SK-OV-3), and epidermoid (KB) carcinomas and skin melanoma (SK-MEL), as well as against noncancerous monkey kidney fibroblasts (VERO) and pig kidney epithelial (LLC-PK₁₁) cells, up to a maximum concentration of 10 µg/mL. Compounds 1–3 also displayed weak antimicrobial and moderate antileishmanial activities against Leishmania donovani promastigotes. These polycyclic ingamine alkaloids represent the first example of antiplasmodial leads without a β-carboline ring, which is known to be responsible for the cytotoxicity of the well-known manzamine class of marine alkaloids related to 1–3.

Key words

Petrosid Ng5 Sp5 - Petrosiidae - ingamine A - 22(S)-hydroxyingamine A - dihydroingenamine D - antiplasmodial

Volltext

Referenzen

References
1 White NJ. A vaccine for malaria. New Engl J Med 2011; 365: 1926-1927
2 Faulkner DJ. Highlights of marine natural products chemistry (1972–1999). Nat Prod Rep 2000; 17: 1-6
3 Sakai R, Higa T, Jefford CW, Benardinelli GJ. Manzamine A, a novel antitumor alkaloid from a sponge. J Am Chem Soc 1986; 108: 6404
4 Samoylenko V, Khan SI, Jacob MR, Tekwani BL, Walker LA, Hufford CD, Muhammad I. Bioactive (+)-manzamine A and (+)-hydroxymanzamine A tertiary bases and salts from Acanthostrongylophora ingnes and their preparations. Nat Prod Commun 2009; 4: 185-192
5 Takasu K, Shimogama T, Saiin C, Kim HS, Wataya Y, Ihara M. π-Delocalized β-carbolinium cations as potential antimalarials. Bioorg Med Chem 2004; 14: 1689-1692
6 Ibrahim MA, Shilabin AG, Prasanna S, Jacob M, Khan SI, Doerksen RJ, Hamann MT. 2-N-Methyl modifications and SAR studies of manzamine A. Bioorg Med Chem 2008; 16: 6702-6706
7 Baldwin JE, Whitehead RC. On the biosynthesis of manzamines. Tetrahedron Lett 1992; 33: 2059-2062
8 Kong F, Andersen RJ, Allen TM. Ingamines A and B, new cytotoxic alkaloids from the marine sponge Xestospongia ingens . Tetrahedron 1994; 50: 6137-6144
9 Kondo K, Shingemori H, Kikuchi Y, Ishibashi M, Sasaki T, Kobayashi J. Ircinals A and B from the Okinawan marine sponge Ircinia sp.: plausible biogenetic precursors of manzamine alkaloids. J Org Chem 1992; 57: 2480-2483
10 Williams DE, Andersen RJ, Holmes C, Allen TM. Motuporin, a potent protein phosphatase inhibitor isolated from the Papua New Guinea sponge Theonella swinhoei Gray. Tetrahedron Lett 1992; 33: 1561-1564
11 Kong F, Andersen RJ, Allen TM. Ingenamine alkaloids isolated from the sponge Xestospongia ingens: Structures and absolute configurations. Tetrahedron 1995; 51: 2895-2906
12 Dale JA, Mosher HS. Nuclear magnetic resonance enantiomeric regents. Configurational correlation via nuclear magnetic resonance chemical shifts of diasteromeric mandelate, O-methylmandelate, and alpha-methoxy-alpha-trifluoromethylphenylacetate (MTPA) esters. J Am Chem Soc 1973; 95: 512-519
13 Sullivan GR, Dale JA, Mosher HS. Chemistry of dihydro-1,3-oxazines. XXI. 1,4- Addition of organometallics to 2-alkenyldihydro-1,3-oxazines. Synthesis of alpha- substituted aldehyde and ketones. J Org Chem 1973; 38: 2143-2147
14 Ohtani I, Kusumi T, Kashman Y, Kakisawa H. High-field FT NMR application of Mosherʼs method. The absolute configurations of marine terpenoids. J Am Chem Soc 1991; 113: 4092-4096
15 Hoye RT, Jeffrey CS, Shao F. Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons. Nat Protoc 2007; 2: 2451-2458
16 Cahn RS, Ingold CK, Prelog V. The specification of asymmetric configuration in organic chemistry. Experientia 1956; 12: 81-94
17 Dou J, McChesney JD, Sindelar RD, Goins DK, Walker LA. A new quassinoid from Castela texana . J Nat Prod 1996; 59: 73-76
18 Makler MT, Ries JM, Williams JA, Bancroft JE, Piper RC, Gibbins BL, Hinrichs DJ. Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity. Am J Trop Med Hyg 1993; 48: 739-741
19 Makler MT, Hinrichs DJ. Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. Am J Trop Med Hyg 1993; 48: 205-210
20 Borenfreund E, Babich H, Martin-Alguacil N. Rapid chemosensitivity assay with human normal and tumor cells in vitro . In Vitro Cell Dev Biol 1990; 26: 1030-1034
21 Mikus J, Steverding D. A simple colorimetric method to screen drug cytotoxicity against Leishmania using the dye AlamarBlue. Parasitol Int 2000; 48: 265-269
22 Rahman A, Samoylenko V, Jain SK, Tekwani BL, Khan SI, Jacob MR, Midiwo JO, Hester JP, Walker LA, Muhammad I. Antiparasitic and antimicrobial isoflavanquinones from Abrus schimperi . Nat Prod Commun 2011; 6: 1645-1650
23 NCCLS. Reference method for broth dilution antifungal susceptibility testing of yeasts, Vol. 22. Approved standard. 2nd edition. Wayne: National Committee for Clinical Laboratory Standards; 2002: 1-51
24 NCCLS. Reference method for broth dilution antifungal susceptibility testing of conidium forming filamentous fungi, Vol. 18. Proposed standard M38-P. Wayne: National Committee for Clinical Laboratory Standards; 1998: 1-39
25 NCCLS. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, Vol. 20. NCCLS Document M7-A5. Wayne: National Committee for Clinical Laboratory Standards; 2000: 1-58
26 NCCLS. Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomycetes, Vol. 20. Tentative standard M24-T2. 2nd edition. Wayne: National Committee for Clinical Laboratory Standards; 2000: 1-81
27 Franzblau SG, Witzig RS, McLaughlin JC, Torres P, Madico G, Hernandez A, Degnan MT, Cook MB, Quenzer VK, Ferguson RM, Gilman RH. Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay. J Clin Microbiol 1998; 36: 362-366
28 Kong F, Andersen RJ. Ingenamine, a novel pentacyclic alkaloid from the marine sponge Xestospongia ingens . Tetrahedron 1994; 35: 1643-1646
29 Kong F, Graziani EI, Andersen RJ. Madangamines B–E, pentacyclic alkaloids from the marine sponge Xestospongia ingens . J Nat Prod 1998; 61: 267-271
30 de Oliveira JH, Grube A, Köck M, Berlinck RG, Macedo ML, Ferreira AG, Hajdu E. Ingenamine G and cyclostellettamines G–I, K, and L from the new Brazilian species of marine sponge Pachyshalina sp. J Nat Prod 2004; 67: 1685-1689
31 Cavalcanti BC, Sombra CM, de Oliveira JH, Berlinck RG, de Moraes MO, Pessoa C. Cytotoxicity and genotoxicity of ingenamine G isolated from the Brazilian marine sponge Pachychalina alcaloidifera . Comp Biochem Physiol C 2008; 147: 409-415
32 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997; 23: 3-25

Zusatzmaterial

Supporting Information