Efecto citotóxico de diterpenos derivados del ácido ent-kaureno aislados de Coespeletia moritziana (Sch. Bip. ex Wedd.) Cuatrec / Cytotoxic effect of ent-kaurene acid-derived diterpenes isolated from Coespeletia moritziana (Sch. Bip. Ex Wedd.) Cuatrec

The objective of the work was to study the cytotoxic effect of ent-kaurene acid derivatives obtained from Coespeletia moritziana (Sch. Bip. Ex Wedd.) Cuatrec., After analysis by GC/MS, IR and NMR. Isolating: kaurenic acid (I), grandifloric acid (II), 15-α-hydroxy kaurenic acid (III), 15 α-acetoxy-kaur 16-en-19-oic acid (IV), Kaurenol (V); and by hemisynthesis: 15,16-epoxy-17-acetoxy-kauran 19-oic acid (VI), 15-oxo-ent-kaur-16-en-19-oic acid (VIII), ester 2,3,4,6 -15-oxo-kaur-16-en-19-oic acid acetyl α-D-pyranosyl tetra-tetra (VII). Cytotoxicity was tested in human cancer cell lines: uterus (HeLa), lung (A-549), breast (MCF-7), African green monkey kidney non-tumor line (Vero) and human peripheral blood mononuclear cells (CMPS). Compound (I) was active against HeLa, A-549 and Vero. Compounds (II and VIII) showed moderate and good (IC50 ≤ 9 µM) cytotoxicity, respectively, against the five cell lines. Compound (V) showed moderate activity against A-549 and compound (VII), slight cytotoxicity against HeLa and A-549. Results that show the cytotoxic specificity of the isolated kaurenes and derivatives of Coespeletia moritzianaand their therapeutic potential.

El objetivo del trabajo fue estudiar el efecto citotóxico de derivados del ácido ent-kaureno obtenidos de Coespeletia moritziana (Sch. Bip. ex Wedd.) Cuatrec., previo análisis mediante GC/MS, IR y RMN. Aislandose: ácido kaurénico(I), ácido grandiflorénico (II), ácido 15-α-hidroxi kaurénico(III), ácido 15 α-acetoxi-kaur 16-en-19-oico (IV), Kaurenol (V); y por hemisíntesis: ácido 15,16-epoxi-17-acetoxi-kauran 19-oico (VI), ácido15-oxo-ent-kaur-16-en-19-oico (VIII), éster 2,3,4,6-tetra acetil α-D-piranosilo del ácido 15-oxo-kaur-16-en-19-oico (VII). La citotóxicidad fue ensayada en líneas celulares cancerosas humanas: útero (HeLa), pulmón(A-549), mama (MCF-7), línea no tumoral de riñón de mono verde africano (Vero) y células mononucleares humanas de sangre periférica (CMPS). El compuesto (I) resultó activo frente a HeLa, A-549 y Vero. Los compuestos (II y VIII), mostraron moderada y buena (IC50≤9µM) citotoxicidad respectivamente, frente a las cinco líneas celulares. El compuesto (V) presentó moderada actividad frente a A-549 y el (VII), leve citotoxicidad frente a HeLa y A-549. Resultados que evidencian la especificidad citotóxica de los kaurenos aislados y derivados de Coespeletia moritzianay su potencial terapéutico.

Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources.

Species of the Celastraceae family are traditionally consumed in different world regions for their stimulating properties. Celastrol, a triterpene methylene quinone isolated from plants of celastraceas, specifically activates satiety centers in the brain that play an important role in controlling body weight. In this work, the antimicrobial activity and mechanism of action of celastrol and a natural derivative, pristimerin, were investigated in Bacillus subtilis. Celastrol showed a higher antimicrobial activity compared with pristimerin, being active against Gram-positive bacteria with minimum inhibitory concentrations (MICs) that ranged between 0.16 and 2.5 µg/mL. Killing curves displayed a bactericidal effect that was dependent on the inoculum size. Monitoring of macromolecular synthesis in bacterial populations treated with these compounds revealed inhibition in the incorporation of all radiolabeled precursors, but not simultaneously. Celastrol at 3 µg/mL and pristimerin at 10 µg/mL affected DNA and RNA synthesis first, followed by protein synthesis, although the inhibitory action on the uptake of radiolabeled precursors was more dramatic with celastrol. This compound also caused cytoplasmic membrane disruption observed by potassium leakage and formation of mesosome-like structures. The inhibition of oxygen consumption of whole and disrupted cells after treatments with both quinones indicates damage in the cellular structure, suggesting the cytoplasmic membrane as a potential target. These findings indicate that celastrol could be considered as an interesting alternative to control outbreaks caused by spore-forming bacteria.

Astragalus species: Insights on its chemical composition toward pharmacological applications.

Astragalus L. is widely distributed throughout the temperate regions of Europe, Asia, and North America. The genus is widely used in folk medicine and in dietary supplements, as well as in cosmetics, teas, coffee, vegetable gums, and as forage for animals. The major phytoconstituents of Astragalus species with beneficial properties are saponins, flavonoids, and polysaccharides. Astragalus extracts and their isolated components exhibited promising in vitro and in vivo biological activities, including antiaging, antiinfective, cytoprotective, antiinflammatory, antioxidant, antitumor, antidiabesity, and immune-enhancing properties. Considering their proven therapeutic potential, the aim of this work is to give a comprehensive summary of the Astragalus spp. and their active components, in an attempt to provide new insight for further clinical development of these xenobiotics. This is the first review that briefly describes their ethnopharmacology, composition, biological, and toxicological properties.

Phytochemicals with Added Value from Morella and Myrica Species.

Terrestrial plants, due to their sessile nature, are highly exposed to environmental pressure and therefore need to produce very effective molecules that enable them to survive all the threats. Myrica and Morella (Myricaceae) are taxonomically close genera, which include species of trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine. For instance, in Chinese or Japanese folk medicine, they are used to treat diarrhea, digestive problems, headache, burns, and skin diseases. A wide array of compounds isolated from different parts of Myrica and/or Morella species possess several biological activities, like anticancer, antidiabetic, anti-obesity, and cardio-/neuro-/hepatoprotective activities, both in vitro and in vivo, with myricanol, myricitrin, quercitrin, and betulin being the most promising. There are still many other compounds isolated from both genera whose biological activities have not been evaluated, which represents an excellent opportunity to discover new applications for those compounds and valorize Morella/Myrica species.

Withanolide-Type Steroids from Withania aristata as Potential Anti-Leukemic Agents.

Leukemia is a blood or bone marrow cancer with increasing incidence in developed regions of the world. Currently, there is an ongoing need for novel and safe anti-leukemic agents, as no fully effective chemotherapy is available to treat this life-threatening disease. Herein, are reported the isolation, structural elucidation, and anti-leukemic evaluation of twenty-nine withanolide-type steroids (1-29) from Withania aristata. Among them, the new isolated withanolides, withaperoxidins A-D (1-4) have an unusual six-membered cyclic peroxide moiety on the withasteroid skeleton as a structural novelty. Their structures have been elucidated by means of spectroscopic analyses, including 2D NMR experiments. In addition, extensive structure-activity relationships and in silico ADME studies were employed to understand the pharmacophore and pharmacokinetic properties of this series of withasteroids. Compounds 15, 16, and 22 together with withaferin A (14) were identified as having improved antiproliferative effect (IC50 ranging from 0.2 to 0.7 µM) on human leukemia HL-60 cell lines compared with the reference drug, etoposide. This cytotoxic potency was also coupled with good selectivity index (SI 33.0-9.2) on non-tumoral Vero cell line and in silico drug likeness. These findings revealed that these natural withasteroids are potential candidates as chemotherapeutic agents in the treatment of leukemia.

Research Advances on Health Effects of Edible Artemisia Species and Some Sesquiterpene Lactones Constituents.

The genus Artemisia, often known collectively as "wormwood", has aroused great interest in the scientific community, pharmaceutical and food industries, generating many studies on the most varied aspects of these plants. In this review, the most recent evidence on health effects of edible Artemisia species and some of its constituents are presented and discussed, based on studies published until 2020, available in the Scopus, Web of Sciences and PubMed databases, related to food applications, nutritional and sesquiterpene lactones composition, and their therapeutic effects supported by in vivo and clinical studies. The analysis of more than 300 selected articles highlights the beneficial effect on health and the high clinical relevance of several Artemisia species besides some sesquiterpene lactones constituents and their derivatives. From an integrated perspective, as it includes therapeutic and nutritional properties, without ignoring some adverse effects described in the literature, this review shows the great potential of Artemisia plants and some of their constituents as dietary supplements, functional foods and as the source of new, more efficient, and safe medicines. Despite all the benefits demonstrated, some gaps need to be filled, mainly related to the use of raw Artemisia extracts, such as its standardization and clinical trials on adverse effects and its health care efficacy.

Stereoselective Synthesis of Highly Substituted Tetrahydropyrans through an Evans Aldol-Prins Strategy.

A direct and general method for the synthesis of naturally occurring 2,3,4,5,6-pentasubstituted tetrahydropyrans has been developed, employing ß,γ-unsaturated N-acyl oxazolidin-2-ones as key starting materials. The combination of the Evans aldol addition and the Prins cyclization allowed the diastereoselective and efficient generation of the desired oxacycles in two fashions: a one-pot Evans aldol-Prins protocol, in which five new σ bonds and five contiguous stereocenters were straightforwardly generated, and a two-step version, which additionally permitted the isolation of ß,γ-unsaturated alcohol precursors bearing an N-acyl oxazolidin-2-one in the α position. From these alcohols were also obtained halogenated pentasubstituted tetrahydropyrans as well as 2,3,4,5-tetrasubstituted tetrahydrofurans, shedding light on the mechanism of the process. Computational studies were consistent with the experimental findings, and this innovative Evans aldol-Prins strategy was performed for the preparation of a battery of more than 30 densely substituted tetrahydropyrans, unprecedentedly fused to a 1,3-oxazinane-2,4-dione ring, both in a racemic fashion and in an enantiomeric fashion. These novel molecules were successfully submitted to several transformations to permit simple access to a variety of differently functionalized tetrahydropyrans. Most of these unique molecules were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria and the yeast Candida albicans, and some structure-activity relationships were established.

Structure-based design, synthesis, and biological evaluation of withaferin A-analogues as potent apoptotic inducers.

Apoptosis inducers represent an attractive approach for the discovery and development of anticancer agents. Herein, we report on the development by molecular fine tuning of a withaferin A-based library of 63 compounds (2-64), 53 of them reported for the first time. Their antiproliferative evaluation on HeLa, A-549 and MCF-7 human tumor cell lines identified fifteen analogues displaying higher activity (IC50 values ranging 0.3-4.8 µM) than the lead (IC50 values ranging 1.3-10.1 µM) either in lag or log growth phases. SAR analysis revealed that acylation enhances cytotoxicity, suggesting the hydrophobic moiety contributes to the activity, presumably by increasing affinity and/or cell membrane permeability. Further investigation clearly indicated that compounds 3, 11, 12, and 18 induce apoptosis evidenced by chromatin condensation, phosphatidylserine externalization, and caspase-3 activation effects on HeLa cells. The potent capacity to induce apoptosis with concomitant cell loss in G2/M highlights the potential of 27-benzyl analogue (18) as an apoptotic inducer drug candidate.

Chemical composition and biological activity of essential oil of achyrocline ramosissima briton ex rusby (asteraceae) / Composición química y actividad biológica del aceite esencial de achyrocline ramosissima britton ex rusby (asteraceae)

Essential oil from fresh aerial parts of Achyrocline ramosissima Britton ex Rusby (Asteraceae) collected in the Venezuelan Andes was obtained by hydrodistillation and analyzed by GC/MS. A yield of 0.10 percent w/v was afforded, and thirty seven components were identified by comparison of their retention indices (RI) and mass spectra with the Wiley GC-MS Library Data. The major components identified were rosifoliol (31.69 percent), beta-caryophyllene (8.61 percent), guaiol (3.95 percent), beta-eudesmol (3.33 percent) and selina-3,7 (11)-diene (2.99 percent). Antimicrobial activity of A. ramosissima essential oil was also evaluated against Gram positive, Gram negative bacterial strains and Candida albicans yeast. The results showed that, this oil is effective against Gram positive bacteria Staphylococcus aureus ATCC 6538 with MIC values ranging from 50 to 100 μg/mL and MBC values > 200 μg/mL as well as Bacillus subtilis CECT 39 with MIC values of 50 μg/mL and MBC of 100 μg/mL, however a low activity was observed against Gram negative bacterial strains, Pseudomonas aeruginosa AK 958, Escherichia coli CECT 99 and C. albicans yeast performing MIC and MBC values > 200 μg/mL. Cytotoxic activity was also determined against HeLa (cervix carcinoma), A-459 (lung carcinoma), MCF-7 (breast adenocarcinoma) human cancer cell lines and against normal Vero cells (African green monkey kidney), exhibiting antiproliferative effects with IC50 values of 28.2 μg/mL (HeLa cells). This is the first report regarding the chemical composition, antibacterial and cytotoxic activities of the essential oil from this species.

El aceite esencial de las partes aéreas frescas de Achyrocline ramosissima Britton ex Rusby (Asteraceae) recolectada en los Andes venezolanos fue extraído por hidrodestilación y analizado por CG/EM. Se obtuvo un rendimiento de 0,10 por ciento m/v, treinta y siete componentes fueron identificados por comparación de los índices de retención (IR) y sus espectros de masas con los datos de la biblioteca Wiley GC-MS. Los principales componentes identificados fueron rosifoliol (31,69 por ciento), beta-cariofileno (8,61 por ciento), guaiol (3,95 por ciento), beta-eudesmol (3,33 por ciento) y selina-3,7 (11)-dieno (2,99 por ciento). La actividad antimicrobiana del aceite esencial de A. ramosissima fue evaluada contra cepas bacterianas Gram positivas, Gram negativas y la levadura Candida albicans. Los resultados mostraron que el aceite esencial fue activo contra las bacterias Gram positivas Staphylococcus aureus ATCC 6538 con una CIM entre 50-100 μg/mL y CBM de valores > 200 μg/mL y Bacillus subtilis CECT 39 con CIM de 50 μg/mL y CBM de 100 μg/mL, sin embargo se observó una baja actividad contra las cepas bacterianas Gram negativas Pseudomonas aeruginosa AK 958, Escherichia coli CECT 99 y la levadura C. albicans cuyos valores de CIM y CBM fueron > 200 μg/mL. La actividad citotóxica fue determinada frente a las líneas celulares cancerígenas HeLa (carcinoma de cuello uterino), A-459 (carcinoma de pulmón), MCF-7 (adenocarcinoma de mama) y frente a las células normales Vero (células renales de mono verde), mostrando efectos antiproliferativos con valores de CI50 28.2 μg/mL frente a las células HeLa. Este es el primer reporte sobre la composición química, actividad antibacteriana y citotóxica del aceite esencial de esta especie.

Elaeodendron orientale as a source of cytotoxic cardenolides.

In the present study, we report six cardiac glycosides (1-6) along with four known ones (7-10) isolated from the leaves and fruits of Elaeodendron orientale. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and the absolute configuration of 1 was determined by X-ray diffraction analysis. The compounds were evaluated for growth inhibitory activity against a panel of human cancer cell lines, HeLa, A-549, MCF-7 and HL-60, and normal Vero cells. Four compounds from this series (5 and 7-9, IC50 values ranging from 0.01 to 0.07µM) exhibited cytotoxicity against three of the cancer cell lines assayed that was similar to or higher than the well-known therapies digoxin and digitoxigenin. Taking into account the narrow safety range of cardiac glycosides used in clinic, this series shows a selectivity index higher than 3 for three of the cancer cell lines assayed, increasing their interest for further study.

Cytotoxic diterpenes from roots of Crossopetalum gaumeri, a Celastraceae species from Yucatan Peninsula.

Four new diterpenes, crossogumerins A-D (1-4) along with six known ones (5-10) were isolated from the root bark of Crossopetalum gaumeri, an endemic medicinal plant from the Yucatan Peninsula. Their structures were elucidated on the basis of 1D and 2D NMR techniques, including HMQC, HMBC, and ROESY experiments. Compounds 1-5, 8-10 were evaluated for cytotoxicity against HeLa (carcinoma of the cervix) and Hep-2 (lung carcinoma) human tumor cells lines and against normal Vero cells (African green monkey kidney) in lag and log phase of growth. Podocarpane diterpenes, crossogumerin B (2) and nimbiol (10), exhibited the highest activity against HeLa cells (IC50 values of 3.1 and 8.1 µM, respectively), but also selectivity on Vero cells (SI 22.6 and 7.5, respectively). The preliminary SAR studies suggest that an epoxy moiety in ring B and a hydrogen bond-donor group strategically positioned in the diterpene core are important requirements for cytotoxicity and selectivity.

Chemical composition and biological activity of Conyza bonariensis essential oil collected in Mérida, Venezuela.

The essential oil from aerial parts of Conyza bonariensis (L) Cronquist collected in Mérida was obtained by hydrodistillation and analysed by GC/MS. The major components were trans-beta-farnesene (37.8%), trans-ocimene (20.7%) and beta-sesquiphellandrene (9.8%). Cytotoxicity assay was also performed with the essential oil against HeLa (cervix carcinoma), A-459 (lung carcinoma) and MCF-7 (breast adenocarcinoma) human cell lines and against normal Vero cells (African green monkey kidney) with IC50 values ranging from 1.4 to 45.8 microg/mL. Additionally, the essential oil presented a significant bactericidal effect against Bacillus cereus, while a moderate activity was observed against Staphylococcus epidermidis and Candida albicans.

Withaferin A-related steroids from Withania aristata exhibit potent antiproliferative activity by inducing apoptosis in human tumor cells.

Six new withanolides (1-6) along with eleven known ones (7-17) were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Semisynthesis of the minority metabolites 7 and 15 from compounds 6 and 9, respectively, as starting material, was performed. The isolated compounds as well as three derivatives (7a, 9a and 9b) of withaferin A were evaluated for cytotoxicity against HeLa (carcinoma of the cervix), A-549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines, and against normal Vero cells (African green monkey kidney). Five compounds from this series (8, 9a, 9b, 11 and 13) exhibited potent antiproliferative effects on the tumor cells, even higher than the well known anticancer agent, withaferin A (9). Phosphatidylserine externalization, chromatin condensation, and caspase-3 activation clearly indicated apoptosis as a mechanism of action. The structure-activity relationship revealed valuable information on the pharmacophore for withanolide-type compounds.

A new natural spiro heterocyclic compound and the cytotoxic activity of the secondary metabolites from Juniperus brevifolia leaves.

A new natural spiro compound 3,4-dehydrotheaspirone and the known arctiol [1ß,6α-dihydroxy-4(14)-eudesmene] were isolated from Juniperus brevifolia. Arctiol is reported for the first time in the Juniperus genus. Their structures were established by 1D, and 2D NMR and MS spectra. Antimicrobial and cytotoxic activities of 1 and several secondary metabolites 3,4,5,6,7,8,9,10,11,12 previously isolated by our group from J. brevifolia were evaluated and some SAR has been established. The 18-hydroxydehydroabietane (4) displayed great antiproliferative activity against cancer cell lines tested, namely HeLa, A-549 and MCF-7. Compound 4 also presented a significant bactericidal effect against Bacillus cereus at different concentrations tested.

Antibacterial properties of phenolic triterpenoids against Staphylococcus epidermidis.

Two phenolic triterpenoids, pristimerol (30 µg/mL) and 8- EPI-6-deoxoblepharodol (20 µg/mL), obtained by catalytic reduction of pristimerin, exhibited bacteriostatic action against Staphylococcus epidermidis. This activity was not dependent on the inoculum size and the growth phase although it showed a stronger effect when cells were growing actively. Addition of phenolic triterpenoids to S. epidermidis cultures in the log-phase of growth led to an inhibitory effect on incorporation and uptake of radiolabeled precursors thymidine, uridine, leucine, and N-acetyl-glucosamine after 30 min of treatment. Furthermore, a clear release of UV-absorbing material and leakage of intracellular potassium were also detected. These findings, coupled with the high lipophilicity of these molecules, shown by high ClogP values, suggest that 8-EPI and pristimerol are able to interact within the lipid bilayer and as a consequence cause functional alterations on the cytoplasmic membrane of S. epidermidis cells.

Withanolides from Withania aristata and their cytotoxic activity.

Seven new withanolides (1-7), along with three known ones (8-10), were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 2D NMR experiments and spectrometric techniques, and the absolute configuration of 1 and 2 was established by CD analysis. In the search for new cytotoxic compounds from Withania species, the isolated compounds 1-9, along with two derivatives, were assayed for their cytotoxicity against HeLa, MCF-7 and A-549 human tumor cell lines. Derivative (4S,20R,22R)-27-acetoxy-4-p-bromobenzoyloxy-1-oxo-witha-2,5,16,24-tetraenolide (13) showed cytotoxicity against all the cell lines assayed with IC(50) values ranging from 2.8 to 3.6microM, and (4S,20R,22R)-4,27-diacetoxy-4-hydroxy-1-oxo-witha-2,5,16,24-tetraenolide (12) exhibited an IC(50) value of 5.4microM on the MCF-7 cell line.

Semisynthesis and biological evaluation of abietane-type diterpenes. Revision of the structure of rosmaquinone.

The new aromatic diterpenes 7beta-O-benzylrosmanol (3), 7beta-O-benzyl-11,12-di-O-methylrosmanol (4), and 7alpha-thiophenylcarnosic acid (5) have been obtained by partial synthesis from carnosol (1), an abundant natural diterpene present in Salvia species. The structures of these compounds were established from their physical and spectroscopic data. The known diterpenes sagequinone methide A (6), 7beta-O-methylrosmanol (7), 7-O-methylrosmanol (8), and rosmaquinone B (9) were obtained from rosmanol (2). The spectroscopic data of these semisynthetic diterpenes were identical to data reported in the literature. In addition, the new semisynthetic isorosmaquinone (10) was obtained from isorosmanol (12). The proton resonances of rosmaquinone (11) are reassigned based on 2D NMR spectroscopy. These compounds, as well as eight known analogues, were evaluated for cytotoxic and antimicrobial activities.

Cytotoxic activity of diterpenes and extracts of Juniperus brevifolia.

The hexane, dichloromethane, acetone and ethanol extracts of the leaves, bark and wood of Juniperus brevifolia were subjected to screening against human tumour cells lines from the cervix (HeLa) and larynx (Hep-2) in two different stages of the cell cycle. The dichloromethane and the chloroform-soluble portions of the acetone extracts of the leaves were active against both tumour cell lines. Chemical investigation of one of the most active extracts (dichloromethane extract from leaves) by preparative chromatography afforded compounds 1-10. Among these, compounds 1-3 were isolated for the first time from the Juniperus genus (18-hydroxyferruginol, 6,7-dehydrototarol and 7alpha-hydroxytotarol) while 4 and 5 are rare as natural products corresponding to (E)- and (Z)-isomers of 8alpha-hydroxy-labda-13(16),14-dien-19-yl-coumarate, respectively. The structures of all compounds were established based on various spectral data. The cytotoxic activity was evaluated for the first time for compounds 1-5 against HeLa and Vero cell lines in lag and log phases of growth. Compound 5 was shown to be active and selective to HeLa in the log phase.

Cytotoxic activity of lignans from Hibiscus cannabinus.

The antimicrobial and cytotoxic activities of six lignans isolated from the core and bark acetone extracts of Hibiscus cannabinus have been investigated. Two compounds (2 and 3) showed strong cytotoxic activity against HeLa, Hep-2 and A-549 cell lines while compound 5 showed moderate activity on HeLa cells when they were in advanced stage of cellular division. The compounds did not exhibit antimicrobial activity.

Cytotoxic sesquiterpenes from Aplysia dactylomela.

Three new chamigrenes, compound 1, acetyldeschloroelatol 2 (2-bromo-1,1,9-trimethyl-5-methylenespiro[5.5]undec-8-en-3-yl acetate), and acetylelatol 4 (2-bromo-8-chloro-1,1,9-trimethyl-5-methylenespiro[5.5]undec-8-en-3-yl acetate), and the known metabolites deschloroelatol 3, elatol 5, 8-acetylcaespitol 6, and caespitol 7 have been isolated from the sea hare Aplysia dactylomela. The structures of 1, 2, and 4 were determined on the basis of spectroscopic evidences. The in vitro cytotoxicity of six of these compounds against two cancer cell lines (HeLa and Hep-2) and nontumoral Vero cells was evaluated. The results support the hypothesis that the acetate derivatives decrease the toxicity of the corresponding alcohols in a strategy to store toxic metabolites acquired through the diet.