ASIAN JOURNAL OF CHEMISTRY ASIAN JOURNAL OF CHEMISTRY http://dx.doi.org/10.14233/ajchem.2014.17377 INTRODUCTION Marine sponges are one of the richest sources of potential secondary metabolites in the marine environment. Aaptamine (1) with a 1H-benzo[de][1,6]naphthyridine skeleton 1 is one of the potential secondary metabolites marine alkaloid which have remarkable biological properties. HN N O O Structure of aaptamine Aaptamine (1) was initially isolated by Nakamura et al. 2 from the marine sponge Aaptos aaptos, collected off the shores of Okinawa. There are few of aaptamine-type alkaloids that have been isolated from Aaptos aaptos included isoaaptamine 3 , 4-methylaaptamine 4 , bisdimethylaaptamine 5 , bisdimethyl- aaptamine-9- O-sulfate 5 , aaptosine 6 , 3-(phenethylamino) demethyl(oxy)aaptamine 7 and 3-(isopentylamino)demethyl (oxy)aaptamine 7 . Aaptamine and its congeners exhibit a broad spectrum of biological activities such as α-adrenoceptor inhibitor 2 , anti-HSV-1 4 , antineoplastic 8,9 , antimicrobial 3,10 and cytotoxicity against cancer cell lines 11 . Aaptamine itself has good potential as a lead compound from which various deri- vatives can be synthesized. This prompted us to further explore Synthesis and Antibacterial Study of Aaptamine Derivatives FATIN NUR AIN ABDUL RASHID 1 , ASNUZILAWATI ASARI 1,2,* , HABSAH MOHAMAD 2 and SITI MARIAM MOHD NOR 3 1 School of Fundamental Science, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia 2 Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia 3 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia *Corresponding author: E-mail: asnu@umt.edu.my Received: 12 February 2014; Accepted: 5 May 2014; Published online: 25 September 2014; AJC-16035 Aaptamine is a bioactive marine alkaloid containing a unique of 1H-benzo[de][1,6]naphthyridine skeleton. Aaptamine was isolated from marine sponge, Aaptos aaptos and was proposed as starting material for semi-synthetic modifications. A series of aaptamine derivatives were synthesized which consisted of 1,4-dialkyl (2-7), 4-alkyl (8-10) and 9-O-butyryl-1,4-dialkyl (11-16) aaptamine derivatives. Each derivative was characterized by FT-IR, UV-visible, NMR and MS. The synthesized compounds were evaluated for their antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Bacillus cereus, Staphylococcus aureus and Micrococcus sp. bacterial strains using the disc-diffusion method. Some of the derivatives showed potent antibacterial activity against certain bacterial strains. Keywords: Aaptamine, Antibacterial, Disc-diffussion method. the chemistry of this group of compound. Consequently, some new 1,4-dialkyl (2-7), 4-alkyl (8-10) and 9-O-butyryl-1,4- dialkyl (11-16) aaptamine derivatives have been synthesized in our laboratory and their antibacterial activity are reported herein. EXPERIMENTAL All reagents were obtained from Sigma-Aldrich Co., Merck Chemical Co. as well as Acros Organics Co. and were used without additional purification. The reactions were moni- tored by thin layer chromatography (TLC) using plastic precoated sheets (Silica gel 60 F254, 0.25 mm thick). Plates were visualized under UV 365 nm and UV 254 nm without treatment. Column chromatography was performed on silica gel 60 (230-400 mesh, Merck). Melting points were determined using Stuart-Scientific SMP3 apparatus and are uncorrected. Infrared spectra were recorded on Perkin Elmer 100 FT-IR Spectrometer. UV-visible spectra were recorded on Shimadzu UV-1601PC Spectrophotometer. 1 H and 13 C NMR spectra were recorded on either Bruker FT-400 (400 MHz) or Jeol (500 MHz) Spectrometer, using CD3OD as the solvent. Isolation of aaptamine: The marine sponges, Aaptos aaptos (934 g) were collected via scuba diving at a depth of 5 to 10 meters from the islands in Terengganu. The sponges were freeze-dried and later ground into powder. The powdered samples (245.20 g) were extracted with methanol followed by solvent evaporation by rotary evaporator. Aaptamine (1) Asian Journal of Chemistry; Vol. 26, No. 20 (2014), 6903-6907