Microbial Transformation of Bioactive Anthraquinones – a Review

BIOSCIENCES BIOTECHNOLOGY RESEARCH ASIA, December 2013. Vol. 10(2), 577-582

Microbial Transformation of Bioactive Anthraquinones – A Review

Sadia Sultan1,2*, Nurunajah Ab. Ghani2,3, Syed Adnan Ali Shah1,2, Nor Hadiani Ismail2,3, Mohd Zaimi Noor1,2 and Humera Naz1,2*

1Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA(UiTM) Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia. 2Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Level 9, FF3, Universiti Teknologi MARA (UiTM) Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia. 3Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor D.E., Malaysia.

DOI: http://dx.doi.org/10.13005/bbra/1167

(Received: 25 May 2013; accepted: 27 July 2013)

Anthraquinones, especially hydroxyanthraquinones, constitute one of the most ubiquitous classes of naturally occurring phenolic compounds. The hydroxyl and aminoanthraquiones show diverse physiological and pharmacological activity. Since pharmacological studies of small molecule bioactive compounds are known to be hampered by their weak solubility in water, it is important to prepare water-soluble analogues of hydroxy- and aminoanthraquinones by biotransformation. This review summarizes the glucosidation of substituted anthraquinones to achieve soluble analogues using fungi.

Key words: Anthraquinone, biotransformation, fungi, glycoside.

Anthraquinones isolated from the natural product analogs. This new generation of natural sources or as synthetic derivatives have been products relies upon the structural diversification widely used in many applications such as dyes, of complex phytomolecules through different laxatives and also shown to have a wide range means, one of which is biotransformation. of biological activities such as antimicrobial, Biotransformation can be defined as regioselective antifungal, antibiotic, antioxidant, anticancer1-5, and stereospecific chemical transformations that antiviral6-7, antitumor8 and antimalarial9-10. Their are catalyzed by biological systems such as fungi, pharmaceutical applications hindered because bacteria or plant cell cultures through their effective of insolubility. Increasing their solubility would multi-enzymatic systems. Biotransformation has enhance their potential usefulness. been progressively utilized as a means to create In recent years, a second generation of notable therapeutic compounds by doing “what phytopharmaceuticals with altered molecular nature hasn’t done yet”11. It allows changes in structures has gained worldwide recognition due areas of phytomolecules that are not realistically to their improved pharmaceutical properties, attainable by chemical semi-synthesis. The such as lower toxicity, improved solubility and reactions involved in the biotransformation of pharmacokinetics. These are primarily natural organic compounds include oxidation, reduction, hydroxylation, esterification, methylation, isomerization, acetylation and glycosidation12-20. Herein we wish to highlight efficient * To whom all correspondence should be addressed. procedures to prepare O- and N-glycosides of E-mail: [email protected] hydroxyl- and aminoanthraquinones utilizing a convenient microbial transformation method. 578 Sultan et al., Biosci., Biotech. Res. Asia, Vol. 10(2), 577-582 (2013)

Biotransformation of hydroxyanthraquinones of this anthraquinone using the fungi; Absidia Chrysophanol (1: 1,8-dihydroxy-3- coerulea and Mucor spinosus resulted in the methylanthraquinone) is a natural anthraquinone production of chrysophanol-8-O-glucoside (10)23-24 isolated from, Colubrina greggii and has been which showed good antiplatelet and anticoagulant identified as a good antimicrobial and anti- activities25. (Figure 1) inflammatory agent21-22. Microbial transformation

OH O OH O Absidia coerulea HO o HO O O OH 48h, 150 rpm, 27 C OH Mucor spinosus CH3 5 days, 150 rpm, 28oC O CH3 O 1 10 Fig. 1. Microbial biotransformation of chrysophanol (1) by Absidia coerulea and Mucor spinosus.

The same fungus Absidia coerulea has 1-O-β-D-glucopyranoside 1123 after 2 days of successfully been used to transform aloe-emodin 2 incubation in the selected medium. (Figure 2). into its glucoside-derivative namely aloe-emodin-

HO O HO OH O OH OH OH O O Absidia coerulea o CH2OH 48h, 150 rpm, 270 C O CH2OH O 2 11 Fig. 2: Microbial biotransformation of aloe-emodin (2) by Absidia coerulea

Physcion (3: 1,8-dihydroxy-3-methoxy- glucopyranoside(12) and physcion-8-O-β-D- 6-methyl-9,10-anthraquinone), an antibacterial glucopyranoside (13)24, while the same compound and antifungal agent26-27 on transformation by using Absidia coerulea produced only compound Mucor spinosus yielded physcion-1-O-β-D- 1323. (Figure 3)

HO OH OH O O O OH OH OH O OH H3CO CH3 Mucor spinosus O o 12 H3CO CH3 5 days, 150 rpm, 28 C OH O Ab + sid 3 ia HO O 5 d coe ay rul HO O O OH s, 1 ea OH 50 rpm , 2 8 oC

H3CO CH3 O 13

Fig. 3. Microbial biotransformation of physcion (3) by Mucorspinosus and Absidia coerulea Emodin (4: 1,6,8-trihydroxy-3- in the presence of Absidia coerulea (Figure 4) methylanthraquinone), a new potent anticancer produced a glycoside anthraquinone namely anthraquinone28 isolated from the root and rhizome emodin-6-O-β-glucopyranoside (14)23 (Figure 4). of Rheum palmatum L on incubation for 48 hours Sultan et al., Biosci., Biotech. Res. Asia, Vol. 10(2), 577-582 (2013) 579

OH O OH OH O OH Absidia coerulea OH o HO CH3 48h, 150 rpm, 27 C O CH3 O O HO O HO OH 4 14

Fig. 4. Microbial biotransformation of emodin (4) by Absidia coerulea

The famous traditional Chinese medicine rhein (5) using Beauveria bassiana (Figure 5) as a rhein (5)24; an anthraquinone found in cassia tool has produced anthraquinone glycoside; 7-O- fistulah shows good antifeedent, anticancer and (42 -methoxy-β-D-glucopyranoside) aloe-emodin antifungal activity29-31. Microbial transformation of (18)32. OH HO O OH O OH OH O OH H3CO OH O Beauveria bassiana

COOH CH2OH O O 5 18

Fig. 5. Microbial biotransformation of rhein (5) by Beauveria bassiana

Another isolated carcinogenic 1-(42 -O-methyl-1β-O-D-glucopyranosyloxy) anthraquinone chrysazin (6: 1,8-dihydroxyan- anthraquinone (16) using Beauveria bassiana34. thraquinone) 22,33 was transformed into 8-hydroxy- (Figure 6)

HO OH OH O OH OH O O O OH CH2OH Beauveria bassiana 7 days, 150 rpm, 25oC

O O 6 16 Fig. 6. Microbial biotransformation of chrysazin (6) by Beauveria bassiana Microbial transformation of alizarin (7: a better antioxidant activity when compared with 1,2-dihydroxyanthraquinone) using Beauveria green tea polyphenol and vitamin E35. In additional, bassiana (Figure 10) has afforded 1-hydroxy- alizarin (7) also showed good cytotoxicity against 2-(42 -O-methyl-2β-O-D-glucopyranosyloxy) osteosarcoma and breast carcinoma cells36. It also anthraquinone (17)34. Alizarin 7 was found to have exhibits immunosuppressive activity37.

O OH O OH OH O HO Beauveria bassiana OH OH 7 days, 150 rpm, 25oC O CH2OH O O 7 17 Fig. 7. Microbial biotransformation of alizarin (7) by Beauveria bassiana 580 Sultan et al., Biosci., Biotech. Res. Asia, Vol. 10(2), 577-582 (2013)

Biotransformation of aminoanthraquinones on incubation for 7 days with Beauveria bassiana 1,2-Diaminoanthraquinone (8) is a non- (Figure 8) afforded 1-amino-2-(42 -O-methyl-2β- polar yellow-orange solid compound mainly used N-D-glucopyranosylamino) anthraquinone (18)34 as an additive and works as a sensor of nitric oxide38

O NH2 O NH2 NH NH HO 2 Beauveria bassiana OH OH 7 days, 150 rpm, 25oC O CH2OH O O 8 18 Fig. 8. Microbial biotransformation of 1,2-diaminoanthraquinone (8) by Beauveria bassiana Similarly biotransformation of 9). 1-Aminoanthraquinone (9) is a good starting 1-aminoanthraquinone (9) with Beauveria bassiana material to produce other products. Product of has produced 1-amino-2-(42 -O-methyl-2β-O-D- it shows good antiinflamatory, and antioxidant glucopyranosyloxy)anthraquinone (19)34 (Figure activities39.

O NH2 O NH2 O HO Beauveria bassiana OH OH 7 days, 150 rpm, 25oC O CH2OH O O 9 19

Fig. 9. Microbial biotransformation of 1-aminoanthraquinone (9) by Beauveria bassiana

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