SUPPLEMENTARY MATERIAL

Two New Cytotoxic Furoquinoline Alkaloids Isolated from Aegle marmelos

(Linn.) Correa

Magdy M. D. Mohammed1,2,*

, Nabaweya A. Ibrahim2, Fatma S. El-Sakhawy

3, Khaled M.

Mohamed2, Doaa A.-H. Deabes

2

1Nucleic Acid Center, Institute of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej

55, DK-5230 Odense M, Denmark.

2Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre,

Dokki-12622, Cairo, Egypt. 3Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Giza, Egypt.

* Correspondence to: E-mail: melhenawy111@gmail.com

Abstract

Two new cytotoxic furoquinoline alkaloids were isolated from the leaves of Aegle

marmelos (Linn.) Correa; one from the total alkaloidal fraction (acid/base shake-out method) of

the CHCl3 extract, and identified as 7,8-dihydroxy-4-hydrofuroquinoline and named trivially as

Aegelbine-A. The other new alkaloid isolated from the pet. ether extract and identified as 4-

hydro-7-hydroxy-8-prenyloxyfuroquinoline and named trivially as Aegelbine-B, together with a

known alkaloid; aegeline and a known phenolic acid; ρ-hydroxybenzoic acid. The structures of

all the isolated compounds were established based on 1D and 2D NMR spectroscopy and HR-

ESI/MS. The cytotoxic activity of the isolated compounds was evaluated in vitro against HepG-

2, PC3, A549 and MCF-7 cell lines. The obtained results revealed promising activity with

structure based relationship which discussed briefly.

Keywords: Aegle marmelos (Linn.) Correa; Rutaceae; furoquinoline alkaloids; cytotoxicity;

structure–activity relationship studies.

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Selected HMBC correlations are indicated by (→) and

1H–

1H COSY correlations are indicated

by bold bonds (▬) for compounds (1 & 2).

S1: 1H-NMR spectrum of compound (1)

S2: 13

C-NMR spectrum of compound (1)

S3: COSY spectrum of compound (1)

S4: DEPT-135 spectrum of compound (1)

S5: HSQC spectrum of compound (1)

S6: HMBC spectrum of compound (1)

S7: HR-ESI/MS spectrum of compound (1)

S8: 1H-NMR spectrum of compound (2)

S9: 13

C-NMR spectrum of compound (2)

S10: COSY spectrum of compound (2)

S11: DEPT-135 spectrum of compound (2)

S12: HSQC spectrum of compound (2)

S13: HMBC spectrum of compound (2)

S14: HR-ESI/MS spectrum of compound (2)

S15: The Cytotoxicity data

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The cytotoxic activity of the isolated compounds.

Samples HepG-2 PC-3 A549 MCF-7

IC50 μg/mL (%*)

Aegeline - (43.2) - (10.4) - (15.3) 73.7 (72.5)

ρ-hydroxybenzoic acid - (32.7) - (0) - (32.2) - (50.7)

Aegelbine-B - (36.1) - (29.1) - (36.5) 63.5 (78.5)

Total alkaloid fraction 52.9 (90.4) - (23.9) - (30.5) 59.5 (83.5)

Aegelbine-A 71.4 (72.9) 72.5 (72.3) - (29.6) 56.5 (81.2)

Adriamycin 21.6 23.8 28.3 26.1

LC50: Lethal concentration of the sample which causes the death of 50 % of cells in 48 hrs.

* Inhibition percent (%) was recorded at 100 ppm.