Studies on the synthesis and the antimicrobial and antioxidant activities of a novel class of fluorescein-based glycosides Mani Rajasekar a , Raman Jegadeesh b , Nanjian Raaman b , Thangamuthu Mohan Das a,⇑ a Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India b Department of Botany, CAS, University of Madras, Guindy Campus, Chennai 600 025, India article info Article history: Received 4 May 2011 Received in revised form 27 July 2011 Accepted 3 August 2011 Available online 16 August 2011 Keywords: Partially protected sugars Glycosides Fluorescein diol Antimicrobial activity Antioxidant activity abstract Facile glycosylation of a fluorescein diol derivative with per-O-acetyl/benzoyl sugar derivatives using BF 3 Et 2 O catalyst resulted in the formation of the expected glycosides in 54–66% yield. The biological screening of the glycosides against different microbes shows good inhibitory activity. The antioxidant activity of the fluorescein-based glycosides shows remarkable inhibition (IC 50 80%). Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Due to the intrinsic properties of the fluorescein moiety re- ported for several fluorescein derivatives in the recent literature, 1 these compounds find a wide range of applications, especially in the fields of drug discovery, gene delivery systems, cancer therapy, neurodegenerative diseases, 2 biosensors, 3–9 bioimaging 10–12 and absorption studies of protein-based indicators. 13,14 Although the first report on a fluorescein derivative appeared during the 19th century, fluorescein chemistry is one of the underdeveloped fields in synthetic organic chemistry. These fluorescent molecules emit longer wavelength light upon excitation at around 500 nm in aque- ous media. Recently, several research groups have used these derivatives as fluorescent tags for several biological molecules, such as, protein, DNA, etc., as well as a reliable platform for many kinds of fluorescence probes. 15 Thus, by making use of the fluores- cent nature of the fluorescein-based sugar derivatives reported in the present work, one can presume that these derivatives are ex- pected to find potential applications in the field of biology. Development of several of our existing front-line drugs 16,17 and organic materials 18,19 are essential and reliable platforms, which are, for the most part, dependent on glycosylated products. More- over, understanding of the relationship that exists between the sugars and bioactive entities shed light on the biological signifi- cance 20,21 of these derivatives. Thus, the synthesis of glycosides be- comes one of the important fields of current research, which is mainly due to their inhibitory activity against several enzymes 22 and their serving as inducers of a-glycosidase. 23 In recent years, several organic derivatives that are reported to have good-to- excellent antioxidant activity belong to the family of flavonoids and fluorescein derivatives. 24,25 However, these classes of com- pounds are either defensive molecules used in the prevention of different pathological disorders or are used in industry for the pre- vention of oxidative damage to polymers and natural pigments. 26 Though several reports 27,28 using BF 3 Et 2 O, TMSOTf, AgClO 4 , among others, have appeared on the synthesis of glycosides, 29–33 to the best of our knowledge, this is the first report on the reaction of per-O-acetylated/benzoyl monosaccharides with fluorescein diol derivatives in the presence of BF 3 Et 2 O as a Lewis acid catalyst. Since fluorescein reacts with lipid radicals 34 to form phenoxy radicals that act as effective chain-breaking antioxidants, we also expect fluorescein diol derivatives to have characteristic antioxi- dant properties. Moreover, alkyl-substituted fluorescein, which in- creases the electron density on the hydroxyl group by an inductive effect, increases its activity toward the generation of lipid radi- cals. 35 Thus it has been proposed that these two potentially useful properties could be combined in a properly functionalized aro- matic alcohol that might act as an efficient drug. 36 In addition to our ongoing research 37,38 in the area of sugar chemistry, here we investigate the influence of the sugar skeleton and glycon motifs on antimicrobial activity by the well diffusion method and deter- mine the antioxidant properties using the 1,1-diphenyl-2-pic- rylhydrazide (DPPH) radical-scavenging activity assay. 0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2011.08.005 ⇑ Corresponding author. Tel.: +91 44 22202814; fax: +91 44 22352494. E-mail address: tmdas_72@yahoo.com (T. Mohan Das). Carbohydrate Research 346 (2011) 2362–2367 Contents lists available at SciVerse ScienceDirect Carbohydrate Research journal homepage: www.elsevier.com/locate/carres