Semi-synthesis and bio-evaluation of polybrominated diphenyl ethers from the sponge Dysidea herbacea T. Srikanth Reddy a , N. Suryakiran a , M. Narasimhulu a , D. Ramesh a , K. Chinni Mahesh a , A. Sai Krishna b , P. Kavitha b , J. Venkateswara Rao b , Y. Venkateswarlu a,⇑ a Natural Products Chemistry Division, Natural Products Laboratory, Indian Institute of Chemical Technology, Hyderabad 500 007, India b Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India article info Article history: Received 6 April 2012 Revised 18 April 2012 Accepted 23 April 2012 Available online 19 May 2012 Keywords: Sponge Dysidea herbacea Polybrominated diphenyl ethers Semi-synthesis abstract The sponge Dysidea herbacea was collected from the Mandapam Coast, Tamilnadu, India. Isolated gram quantities of hydroxylated polybrominated diphenyl ether (HO-PBDE) and semi-synthesized a series of new PBDEs derivatives and tested them for antibacterial and cytotoxic activities. Ó 2012 Elsevier Ltd. All rights reserved. Polybrominated diphenyl ethers (PBDEs) are widely used in com- mercial and industrial products for fire prevention. 1,2 Hydroxylated polybrominated diphenyl ethers (HO-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) have been found in water sewage samples, 3 and even in human blood and breast milk. 4,5 These compounds are lipophilic and can be bio-accumulated via the food chain. 6 The potential toxic effects of PBDEs include thy- roid hormone disruption, 7–10 neurodevelopment discrepancy and cancer. 11 However, PBDEs also pose antibacterial, antifungal, and cytotoxic activities. 12–14 PBDEs are produced by marine organisms such as sponges, 15,16 tunicates 17,18 and algae. 19 As part of our inves- tigations of bioactive compounds from marine organisms, 20 we de- scribe here the isolation of an HO-PBDE from the sponge Dysidea herbacea (family Dysidea, order Dictyoceratida) 21–25 and the semi- synthesis from it of a series of new PBDEs derivatives with moderate to good potent cytotoxic activity against leukemia cells and antibac- terial activity against gram positive and gram negative bacteria. The sponge D. herbacea (IIC-631) was collected at a depth of 30 feet by SCUBA diving near the Mandapam Coast, (N 9 o 18 0 ,E 79 o 08 0 ), Tamilnadu, India. It was immediately soaked in methanol. The sponge was gray when alive and yellowish gray in methanol. It was purified by gel filtration chromatography on Sephadex LH-20 followed by silica gel chromatography eluting with hexane–ethyl acetate mixtures to afford HO-PBDE as a white solid, mp 88–90 °C. HO-PBDE is non-hygroscopic and stable at room temper- ature. From the forgoing spectral data the structure of HO-PBDE was established as 2-(2 0 ,4 0 -dibromophenoxy)-4,6-dibromophenol, which was a known polybrominated diphenyl ethers (HO-PBDEs) and previously isolated from the sponge D. herbacea and also syn- thesized from commercially available starting materials. 26,27 We have found the marine sponge D. herbacea to contain good quanti- ties of the HO-PBDE. 28,29 Refluxing HO-PBDE with various alkyl bromides in the presence of K 2 CO 3 in acetone for 6 h followed by workup and silica gel col- umn chromatography gave the corresponding ethers 30 as shown in Scheme 1 and Table 1. All reactions were clean and obtained near quantitative yields. The products include naturally occurring sub- stances MeO-PBDE (A), AcO-PBDE (B). The alkylation was very selective when 5 equiv of bis-functional alkylating agents were used for the alkylation (Table 1, entries 10–14). Similarly, refluxing M with secondary amines in the presence of K 2 CO 3 in acetonitrile for 6 h gave the corresponding PDBE derrivatives 31 as shown in Table 2 and Schemes 2. When the above reaction was carried out in acetone the reaction was incomplete and the obtained yields were low. All the products were characterized by NMR and mass spectral data. O Br Br OH Br Br 1 2 3 4 5 6 1' 2' 3' 4' 5' 6' HO-PBDE O Br Br OR Br Br 1 2 3 4 5 6 1' 2' 3' 4' 5' 6' PBDEs 0960-894X/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bmcl.2012.04.133 ⇑ Corresponding author. Tel.: +91 40 27193167; fax: +91 40 27160512. E-mail address: luchem@iict.res.in (Y. Venkateswarlu). Bioorganic & Medicinal Chemistry Letters 22 (2012) 4900–4906 Contents lists available at SciVerse ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl