Yoel Kashman

Structure of swinholide-A, a new macrolide from the marine sponge Theonella swinhoei

Abstract Swinholide-A ( 1 a) a novel 22-membered macrolide has been isolated from a Red Sea sponge. The structure of the tetraformate ( 1b ) has been determined on basis of spectral data using 2D-NMR correlations.

Hemiasterlin and geodiamolide TA ; two new cytotoxic peptides from the marine sponge hemiasterella minor (Kirkpatrick)

Three cytotoxic peptides, Jaspamide (1) and the two new peptides hemiasterlin (2) and geodiamolide TA (3), have been isolated from the sponge Hemiasterella minor. The structures of the three were determined by interpretating the NMR and mass spectra. Hemiasterlin (2) is a novel linear tripeptide embodying two unique, new natural aminoacids and geodiamolide TA (3) is a higher homologe of geodiamolides A–F.

Latrunculin, a new 2-thiazolidinone macrolide from the marine sponge latrunculia magnifica

Abstract Three new toxins were isolated from the Red Sea sponge Latrunculia magnifica A full structure determination of these toxins, by spectroscopic methods, was aided by an X-ray diffraction analysis of a crystalline derivative ( 1 b) of latrunculin-A. The Latrunculins exhibit a new class of 14 and 16 membered macrolides to which the rare 2-thiazolidinone moiety is attached. A biogenesis of these biologically active compounds is put forward.

Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain

Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic‐like and antide‐pressive‐like behavioral effects in wild‐type (WT) mice with concomitant changes in c‐Fos activation in the brain. These behavioral effects were not noted in TRPV3−/− mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3+/+ mice. It had no effect on keratinocytes from TRPV3−/− mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.—Moussaieff, A., Rimmerman, N., Bregman, T., Straiker, A., Felder, C. C., Shoham, S., Kashman, Y., Huang, S. M., Lee, H., Shohami, E., Mackie, K., Caterina, M. J., Walker, J. M., Fride, E., Mechoulam, R. Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. FASEB J. 22, 3024–3034 (2008)

New glycosphingolipids from marine organisms

Abstract The structure of several ceramides and cerebrosides, from three marine sponges and a soft coral collected in the Red Sea, are reported. Specifically, the structure determination of ptiloceramide, halicerebroside A and amphicerebrosides B-F was achieved following suitable degradations and NMR measurements.

Antitumor macrodiolides isolated from a marine sponge theonella sp.: Structure revision of misakinolide A

Two antitumor macrodiolides, bistheonellides A and B, were isolated from a marine sponge Theonella sp. Bistheonellide A was found to be identical with misakinolide A, whose structure has been revised from the previously proposed monomeric macrolide (3) to the dimeric macrodiolide (1). Similarly, bistheonellide B was deduced to be the related structure 2.

Sarcophine, a new epoxy cembranolide from marine origin

Abstract From the soft bodied coral Sarcophytum glaucum a crystalline compound-sarcophine (1), which is believed to be one of the repellents protecting the coral against predators, was isolated. The functional groups of 1 have been deduced from detailed NMR study and the whole molecular structure has been determined by a single-crystal 3-dimensional X-ray diffraction study proceeding from direct methods. The compound crystallizes in orthorhombic crystals, space group P212121, and there are four molecules in each unit cell of dimensions a = 12·429(3), b = 13·766(3) and c = 10·750(1). The structure was found to be a new epoxy cembranolide. The mass spectrum and CD of 1 and several simple derivatives as well as the conformation of 1 in solution are discussed.

Halitulin, a new cytotoxic alkaloid from the marine sponge Haliclona tulearensis

Abstract Halitulin ( 2 ), a novel bisquinolinylpyrrole has been isolated from the sponge Haliclona tulearensis . Its structure was elucidated mainly on the basis of spectroscopic data as well as chemical modifications. Halitulin was found to be cytotoxic against several tumor cells: P-388, A-549, HT-29 and MEL-28 in concentrations of 12–25 ng/ml.

Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-κBα (IκBα) degradation in tumor necrosis factor (TNF) α-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-κB (NF-κB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IκB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-κB activation. It had no effect on IKK activity in vitro, and it did not suppress IκBα phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-κB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFα-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-κB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

Three new sesquiterpene hydroquinones from marine origin

Abstract Three new sesquiterpene hydroquinones peyssonol A and B (5 and 6 and hyatellaquinone (7) have been isolated from the alga Peyssonnelia sp. and the sponge Hyatella intestinalis. The structure of the three compounds was determined mainly by NMR measurements. Peyssonol A (5) is the first reported bromo sesquiterpene hydroquinone. Several of the new compounds were found in a preliminary test to inhibit the reverse transcriptase of human immunodeficiency virus (HIV).