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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
1   National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA
,
Mohamed A. Ibrahim
1   National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA
2   Department of Chemistry of Natural Compounds, Division of Pharmaceutical and Drug Industries Division, National Research Center, Dokki, Giza, Egypt
,
Shabana I. Khan
1   National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA
3   Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA
,
Melissa R. Jacob
1   National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA
,
Babu L. Tekwani
1   National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA
4   Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA
,
Larry A. Walker
1   National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA
4   Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA
,
Vladimir Samoylenko
1   National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, USA
› Author Affiliations
Further Information

Publication History

received 14 February 2012
revised 06 July 2012

accepted 17 July 2012

Publication Date:
17 August 2012 (online)

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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

Supporting Information

 

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