Total Synthesis and Biological Evaluation of (5<i>Z</i>,9<i>Z</i>)-5,9-Hexadecadienoic Acid, an Inhibitor of Human Topoisomerase I

Carballeira, Néstor M.; Betancourt, José E.; Orellano, Elsie A.; González, Fernando

doi:10.1021/np0202576

Cited by 45 publications

(36 citation statements)

References 12 publications

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“…al. [9]. Reactions (20 µL) that contained a mixture of sterile water, TGS buffer (10 mM Tris-HCl at pH 7.9, mM EDTA, 0.15 M NaCl, 0.1 % BSA, 0.1 mM Spermidine, 5 % glycerol), supercoiled pHOT1 plasmid DNA (0.25 µg/µL in 10 mM Tris-HCl at pH 7.5, 1 mM EDTA), 14-methyl-9Z-pentadecenoic acid (dissolved in DMSO and tested at final concentrations of 1000 µM, 750 µM, 500 µM, 250 µM, 150 µM, 50 µM and 25 µM), and DNA topoisomerase I obtained from human placenta (1 unit can relax 0.25 µg of supercoiled DNA in 30 min at 37 o C) were assembled in sterile microcentrifuge tubes on ice.…”

Section: -Methyl-9z-pentadecen-1-ol (8)mentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9] Topoisomerase I is a key enzyme in the breaking and fixing of DNA strands and is involved in making the necessary topological changes to DNA for key cellular processes such as replication, transcription, and recombination. 1 Topoisomerases have also evolved as key cellular targets for the development of effective anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

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An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid and its topoisomerase I inhibitory activity

Carballeira¹,

Sanabria²,

Oyola³

2006

Arkivoc

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An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid was developed based on the appropriate use of (trimethylsilyl)acetylene as the key reagent in the synthesis. The reported synthesis started with commercially available 8-bromo-1-octanol and furnished the desired acid in seven steps and in a 16% overall yield, a significant improvement over the previous reported synthesis for this fatty acid. The synthesis reported herein afforded sufficient amounts to study the acid topoisomerase I inhibitory potential and it was found that the title acid inhibits the human placenta DNA topoisomerase I enzyme at concentrations of 500 µM.

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Section: -Methyl-9z-pentadecen-1-ol (8)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid and its topoisomerase I inhibitory activity

Carballeira¹,

Sanabria²,

Oyola³

2006

Arkivoc

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“…The main components of sponge membranes, phospholipids, consist of unusual, long-chained fatty acids (Ando et al 1998). Many unusual fatty acids isolated from sponges have potent cytotoxic (Tachibana et al 1981), antimicrobial (Carballeira et al 2002), and antifungal (Fusetani et al 1993) activities. In addition, some branched fatty acids, particularly those with iso, anteiso, cyclopropyl, and monomethyl groups, are suggested to be of bacterial origin and specific to particular bacteria; because of this, they can be used as biological markers for bacterial associates in sponges (Gillian et al 1988).…”

Section: Introductionmentioning

confidence: 99%

Surface bacterial community, fatty acid profile, and antifouling activity of two congeneric sponges from Hong Kong and the Bahamas

Lee¹,

Yang²,

Li³

et al. 2007

Mar. Ecol. Prog. Ser.

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Bacterial communities on the surfaces of 2 congeneric sponges, Mycale adhaerens from Hong Kong and M. laxissima from the Bahamas, were compared using conventional cultivation techniques and terminal restriction fragment length polymorphism (TRFLP) analysis -a cultureindependent DNA fingerprinting technique. The bacterial community on the Hong Kong sponge was more diverse, in terms of the number and type of species isolated, and different from that on the Bahamas sponge, as evident from distinct clusters formed in TRFLP analysis. Distinctive bacterial types (i.e. TRFs) were commonly found on both sponge surfaces, but none of their bacterial isolates were common. At tissue level concentration, extract of the Hong Kong sponge inhibited the growth of a wide range of bacteria isolated from the Hong Kong reference surface, but did not affect any of those isolated from the Bahamas reference surface, indicating highly specific antibacterial activity. Extracts of both sponges, when incorporated into hydrogels and exposed to the natural environment for bacterial film development, dramatically altered the bacterial community in the films, either by shifting the bacterial composition or decreasing bacterial density. Settlement assays of the resulting films using larvae of the polychaete Hydroides elegans showed that the filmed hydrogels with Hong Kong sponge extracts either inhibited larval settlement or were toxic to the larvae; however, those with the Bahamas sponge extracts had no observable effect. HPLC (high performance liquid chromatography) and GC-MS (gas chromatography-mass spectrometry) analyses revealed different chemical profiles in the extracts; the Hong Kong sponge had a more diverse fatty acid profile. Our results suggest that the 2 congeneric sponges from geographically separated regions have 'speciesspecific', surface-associated bacterial communities and antifouling activities, which might be due to the differences in the chemical and fatty acid compositions of the 2 sponges. Alternately, different sponge-associated bacterial communities may reflect habitat differences in sympatric bacterial and fouling communities.

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“…Of all marine animals, sponges have the largest variety of sterols, lipids, and fatty acids (FA) with unusual and sometimes unique structures [1]. Certain unusual sponge lipids possess biological activity [2].According to the literature, lipid and FA compositions of tropical and subtropical sponges are most studied whereas sponges from boreal regions are practically unstudied. Herein the FA composition of total lipids from the Okhotsk Sea marine sponge Forcepia uschakowi is studied for the first time.…”

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Fatty acids from the Okhotsk sea sponge Forcepia uschakowi

Rodkina

2007

Chem Nat Compd

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The fatty-acid (FA) composition of total lipids from the Okhotsk sea marine sponge Forcepia uschakowi was studied. A total of 56 acids were identified by GC and GC-MS. The principal saturated acids were 16:0 and 18:0. The main monoene acid was , which was observed for the first time in sponge lipids. Polyunsaturated acids represented of 64.1% of the total FA of F. uschakowi. Of these, the principal ones were non-methylene-separated acids 26:2(5,9) and 26:3(5,9,19), which are typical of sponges, and bromo-acid 9).The search for new fatty acids, the elucidation of their structures and biosynthetic pathways, and the study of their properties and roles in organisms are currently of great biochemical interest. From this viewpoint, some of the most interesting subjects are representatives of the phylum Porifera. Of all marine animals, sponges have the largest variety of sterols, lipids, and fatty acids (FA) with unusual and sometimes unique structures [1]. Certain unusual sponge lipids possess biological activity [2].According to the literature, lipid and FA compositions of tropical and subtropical sponges are most studied whereas sponges from boreal regions are practically unstudied. Herein the FA composition of total lipids from the Okhotsk Sea marine sponge Forcepia uschakowi is studied for the first time.According to GC analysis, FA from total lipids of F. uschakowi contained more than 70 components. Of these, 56 components (94.8%) were identified (Table 1).Saturated FA made up 10.2% of the total FA from F. uschakowi. The principal saturated acids were 16:0 and 18:0. Saturated FA with a branched carbon skeleton made up 4.3%. These were basically acids with a methyl group in the (n-2) and (n-3) position. Saturated C 15-20 FA of i/ai-structure were observed previously in many sponges and other organisms [3]. It is commonly thought that such acids are of bacterial origin [4]. Saturated FA of isoprenoid structure were observed in small quantities in lipids of F. uschakowi. It is known that acids of isoprene structure are formed by degradation of phytol, which in turn is produced by destruction of chlorophyll [5]. It was shown earlier that isoprene acids in sponges occurred in plasma membranes [6].Monoene FA of linear structure totalled 13.3% of total FA in F. uschakowi. Of these, the principal ones were 16:1(9), 18:1(11), and 22:1(15). Two different monoene FA with one branch in the middle of the chain were observed in the studied sponge. These were 7-Me-16:1(6) (1.6%) and 15-Me-24:1(14) (6.1%). Acid 7-Me-16:1(6) was observed earlier in sponges Trikentnon loeve and Pseudaxinella af. lunaecharta [7] whereas acid 15-Me-24:1(14) was found for the first time in sponge lipids and is probably synthesized in F. uschakowi by elongation of 7-Me-16:1(6).Mass spectra of the pyrrolidide of 15-Me-24:1(14) contained a molecular ion [M] ·+ with m/z 433. A gap of 12 amu occurred between ions of C-13 (m/z 266) and C-14 (m/z 278) fragments. The peak for the C-15 ion (m/z 292) was almost completely absent (0.1%), i.e., a gap of 28 amu oc...

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Total Synthesis and Biological Evaluation of (5Z,9Z)-5,9-Hexadecadienoic Acid, an Inhibitor of Human Topoisomerase I

Cited by 45 publications

References 12 publications

An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid and its topoisomerase I inhibitory activity

An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid and its topoisomerase I inhibitory activity

Surface bacterial community, fatty acid profile, and antifouling activity of two congeneric sponges from Hong Kong and the Bahamas

Fatty acids from the Okhotsk sea sponge Forcepia uschakowi

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