Structure-Activity Relationship (SAR) Studies to Maximize the Activity of Compounds Isolated from Octocorals

This chapter presents some significant study cases on octocoral organisms (Eunicea succinea, Eunicea mammosa, Eunicea knighti, Pseudoplexaura flagellosa, Eunicea laciniata, Antillogorgia elisabethae, Muricea austera, Paragorgia sp., Lobophyton sp., Sarcophyton glaucum and Sinularia lochmodes) that have been identified as a source of promising bioactive compounds and whose results have further been used for studies on structure-activity relationship (SAR) as a strategy to increase the value of the activity initially detected. The scientific literature data discussed here were obtained with the SciFinder tool during the period 2000–2016 and from the additional results here presented for the biofilm inhibition activity of compounds and synthetic analogs for the cases related with Eunicea knighti and Pseudoplexaura flagellosa (until now unpublished data of the authors of this chapter)

Synthesis of Acetylhomoagmatine

The first total synthesis of acetylhomoagmatine, a natural product isolated form the methanolic extracts from the sponge Cliona celata, is performed in four steps in a very high yield.Galicia. Consellería de Innovación, Industria e Comercio; PGIDIT05RMA10302PRColombia.Colciencias; 1101-09-1354

Anti-inflammatory effects of the gorgonian Pseudopterogorgia elisabethae collected at the Islands of Providencia and San Andrés (SW Caribbean)

<p>Abstract</p> <p>Background</p> <p>We are reporting for the first time the <it>in vivo </it>anti-inflammatory activity of extracts and fractions, and <it>in vitro </it>anti-inflammatory activity of pure compounds, all isolated from <it>Pseudopterogorgia elisabethae </it>collected at the Providencia (chemotype 1) and San Andrés (chemotype 2) Islands (SW Caribbean).</p> <p>Methods</p> <p>Extracts from <it>P. elisabethae </it>were fractionated on silica gel to yield fractions: F-1 (pseudopterosins PsQ, PsS and PsU) and F-2 (amphilectosins A and B, PsG, PsK, PsP and PsT and <it>seco</it>-pseudopterosins <it>seco</it>-PsJ and <it>seco</it>-PsK) from chemotype 1, and F-3 (elisabethatrienol, 10-acetoxy-9-hydroxy- and 9-acetoxy-10-hydroxy-amphilecta-8,10,12,14-tetraenes (interconverting mixture) and amphilecta-8(13),11,14-triene-9,10-dione) from chemotype 2. By using preparative RP-HPLC and spectroscopic means, we obtained the pure PsG, PsK, PsP, PsQ, PsS, PsT, PsU, <it>seco</it>-PsK and the interconverting mixture of non-glycosylated diterpenes (IMNGD). The anti-inflammatory properties of extracts and fractions were evaluated using <it>in vivo </it>model "12-<it>O</it>-tetradecanoyl-phorbol-acetate (TPA)-induced mouse ear oedema". The activities of pure compounds and of the IMNGD were evaluated using <it>in vitro </it>assays myeloperoxidase (MPO) release (by human polymorphonuclear neutrophils (PMNs)), nitric oxide release (by J-774 cells) and scavenger activity on NO.</p> <p>Results</p> <p>In the <it>in vivo </it>anti-inflammatory assay, extracts and F-3 showed low inhibition levels of inflammation compared to indomethacin, F-1 and F-2. Additionally, we evaluated the MPO release to the inflammation site, and found a marked inhibition of MPO levels by all extracts and fractions, even superior to the inhibition shown by indomethacin.</p> <p>Furthermore, in the MPO <it>in vitro </it>assay, IMNGD, PsQ, PsS, PsT and PsU, exhibited higher inhibition levels compared to dexamethasone and indomethacin. In the NO release <it>in vitro</it>, IMNGD, PsP and PsT were the most potent treatments. Finally, because the PsG, PsP and <it>seco</it>-PsK did not exhibit any NO scavenger activity, they should inhibit the inducible Nitric Oxide Synthase (iNOS) or other routes that influence this enzyme. Alternatively, PsQ, PsS, and PsU did show scavenger activity.</p> <p>Conclusion</p> <p>All results presented contribute to demonstrate that the compounds isolated in this work from <it>P. elisabethae </it>are promising molecules with an interesting anti-inflammatory activity profile. Additionally, the results obtained could provide preliminary insights towards their structure-activity relationship.</p

Esteróles en esponjas marinas

Esta revisión bibliográfica comprende la mayona del trabajo publicado hasta el momento sobre esteróles aislados de esponjas marinas. Estos esteróles comprenden compuestos desde Cig hasta C31 con estructuras convencionales y con estructuras novedosas (núcleo y/o cadena lateral no convencional)

Composición esterólica de la esponja marina xestospongia muta

De la esponja marina Xestospongia muta recolectada en la bahía de Santa Marta, Caribe Colombiano, se aislaron por Cromatografía en Columna (CC) sobre Silica gel, eluyendo con Benceno: Acetato de Etilo 10:2, dos fracciones esteróiicas; XMl (Rf = 0,28,Si02/Benceno; AcOEt 10:2) y XM2 (Rf = 0,24,SiO2/Benceno : AcOEt 10:2), Los esteróles presentes en estas dos fracciones fueron sometidos a Cromatografía Liquida de Alta Eficiencia (CLAE) preparativa y analizados por Cromatografía de Gases (CG) y Cromatografía de Gases acoplada en Espectometrla de Masas (CG-EM), Catorce esteróles fueron separados y 13 idenficados. La mayoría de ellos fueron 3n-0H-A^-Esteróles (Aproximadamente el 87% de los esteróles totales) incluyendo al (24R + 24S)-5,28-Estigmastadien-3i3-24-diol, mezclaepimérica por primera vez asi reportada en la naturaleza. El porcentaje restante correspondió a Estañóles y a un 6,2% de compuestos sin identificar

Aproximación al estudio de la interacción entre aristolochia maxima y larvas de la mariposa battus polydamas polydamas y parides panares erythrus mediada por ácidos aristolóquicos

Las mariposas de la tribu Troidini (Lepidoptera: Papilionidae) capturan los ácidos aristolóquicos (AAs) provenientes de su alimentación larval en plantas de Aristolochiaceae para su protección. En este estudio se detectó la presencia de los ácidos aristóloquicos I y II (AA-I y AA-II) en hojas jóvenes de Aristolochia maxima (Aristolochiaceae) y en larvas de las mariposas Battus polydamas polydamas y Parides panares erythrus (Papilionidae, Papilioninae) por Cromatografía Líquida de Alta Eficiencia (CLAE). De acuerdo con los resultados de los perfiles cromatógraficos por CLAE, el AA-I fue el ácido aristolóquico mayoritario encontrado tanto en las larvas como en las hojas jóvenes de la planta, seguido por cantidades menores del AA-II. Estos resultados permiten afirmarque la interacción planta-animal entre las mariposas de las especies B. polydamas y P. panares y las plantas de A. maxima, está mediada, por los ácidos aristóloquicos I y II.Most butterflies of the tribe Troidini (Lepidoptera: Papilionidae) sequester aristolochic acids (AA) for their protection. These acids are derived from their host plants -family Aristolochiaceae- upon which they feed on during their larval stages. Using analytical High Performance Liquid Chromatography (HPLC) methods we were able to detect the presence of aristolochic acids I and II both in the young leaves of Aristolochia maxima (Aristolochiaceae) and in the caterpillars of the butterflies Battus polydamas polydamas and Parides panares erythrus (Papilionidae, Papilioninae). Aristolochic acid I was the major constituent found, followed by lesser amounts of Aristoloquic acid II. These results confirm that the host-animal interaction among butterflies of the studied species and A. maxima plants is mediated, by aristolochic acids

Cytotoxic and Antimicrobial Activity of Pseudopterosins and seco-Pseudopterosins Isolated from the Octocoral Pseudopterogorgia elisabethae of San Andrés and Providencia Islands (Southwest Caribbean Sea)

To expand the potential of pseudopterosins and seco-pseudopterosins isolated from the octocoral Pseudopterogorgia elisabethae of San Andrés and Providencia islands (southwest Caribbean Sea), we report the anti-microbial profile against four pathogenic microorganisms (Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans) and report a more complete cytotoxic profile against five human cells lines (HeLa, PC-3, HCT116, MCF-7 and BJ) for the compounds PsG, PsP, PsQ, PsS, PsT, PsU, 3-O-acetyl-PsU, seco-PsJ, seco-PsK and IMNGD. For the cytotoxic profiles, all compounds evaluated showed moderate and non-selective activity against both tumor and normal cell lines, where PsQ and PsG were the most active compounds (GI50 values between 5.8 μM to 12.0 μM). With respect to their anti-microbial activity the compounds showed good and selective activity against the Gram-positive bacteria, while they did not show activity against the Gram-negative bacterium or yeast. PsU, PsQ, PsS, seco-PsK and PsG were the most active compounds (IC50 2.9–4.5 μM) against S. aureus and PsG, PsU and seco-PsK showed good activity (IC50 3.1–3.8 μM) against E. faecalis, comparable to the reference drug vancomycin (4.2 μM)

Esteroles en esponjas marinas

ABSTRACT: This review covers most of the published work on sterols Isolated from marine sponges. The carbón range of those sterols varíes from C19 to C31 and their structures possess conventlonal and novel nucieus and/or side chalns.RESUMEN: Esta revisión bibliográfica comprende la mayona del trabajo publicado hasta el momento sobre esteróles aislados de esponjas marinas. Estos esteróles comprenden compuestos desde Cig hasta C31 con estructuras convencionales y con estructuras novedosas (núcleo y/o cadena lateral no convencional)