Article

Hyrtioscalaranes A and B, two new scalarane-type sesterterpenes from Hyrtios erectus with anti-inflammatory and antioxidant effects

Authors:
If you want to read the PDF, try requesting it from the authors.

Abstract

Two new scalarane-type sesterterpenes, hyrtioscalaranes A and B, were isolated from the organic extract of the Demosponge Hyrtios erectus through extensive chromatographic purification. Hyrtioscalarane A exhibited significantly greater attenuation property against cyclooxygense-2 (IC50 0.83 mM) than that displayed by hyrtioscalarane B (IC50 0.98 mM). The greater selectivity index of hyrtioscalaranes (> 1) than that exhibited by the commercial anti-inflammatory agent ibuprofen (0.43) further supported the higher selectivity of the former towards pro-inflammatory cyclooxygenase-2. Hyrtioscalarane A exhibited greater antioxidant activities as determined by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50 0.77 mM) and 2,2-diphenyl-1-picrylhydrazyl (IC50 0.81 mM) free radical quenching properties than those displayed by hyrtioscalarane B (IC50 > 0.83 mM) and the antioxidative agent α-tocopherol (IC50 1.51 mM). The greater binding energy (–14.32 kcal/mol) and docking score (15.22 kcal/mol) of hyrtioscalarane A at the active site of cyclooxygenase-2 along with the higher electronic parameters and balanced hydrophobicity could attribute its potential anti-inflammatory activity.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Terpenes, formed by the condensation of two subunits of isoprene (C 5 H 8 ), known also as terpenoids, are antioxidant molecules with a very diverse structure [18]. Two new scalarane-type sester-terpenes, hyrtioscalaranes A and B (see their chemical structure in Figure 6), were isolated by K Chakraborty and Francis [142] from the organic extract of the demosponge Hyrtios erectus through extensive chromatographic purification. ...
... Terpenes, formed by the condensation of two subunits of isoprene (C5H8), known also as terpenoids, are antioxidant molecules with a very diverse structure [18]. Two new scalarane-type sester-terpenes, hyrtioscalaranes A and B (see their chemical structure in Figure 6), were isolated by K Chakraborty and Francis [142] from the organic extract of the demosponge Hyrtios erectus through extensive chromatographic purification. The evaluation of their antioxidant and anti-inflammatory effects showed that hyrtioscalarane A exhibits greater antioxidant activity (ABTS, DPPH free radical quenching) than hyrtioscalarane B and the antioxidant α-tocopherol. ...
... The evaluation of their antioxidant and anti-inflammatory effects showed that hyrtioscalarane A exhibits greater antioxidant activity (ABTS, DPPH free radical quenching) than hyrtioscalarane B and the antioxidant α-tocopherol. Both hyrtioscalaranes A and B display a higher selectivity index (>1) than the commercial antiinflammatory agent ibuprofen (0.43) [142]. The antioxidant potential of the monoterpenoid (−)-Loliolide, isolated from seaweed Sargassum horneri, was revealed by Kim et al. [143] in Vero cells and in zebrafish models. ...
Article
Full-text available
Background: The well-recognized but not fully explored antioxidant activity of marine-biota-derived, biologically active substances has led to interest in their study as substitutes of antibiotics, antiaging agents, anticancer and antiviral drugs, and others. The aim of this review is to present the current state of the art of marine-biota-derived antioxidants to give some ideas for potential industrial applications. Methods: This review is an update for the last 5 years on the marine sources of natural antioxidants, different classes antioxidant compounds, and current derivation biotechnologies. Results: New marine sources of antioxidants, including byproducts and wastes, are presented, along with new antioxidant substances and derivation approaches. Conclusions: The interest in high-value antioxidants from marine biota continues. Natural substances combining antioxidant and antimicrobial action are of particular interest because of the increasing microbial resistance to antibiotic treatments. New antioxidant substances are discovered, along with those extracted from marine biota collected in other locations. Byproducts and wastes provide a valuable source of antioxidant substances. The application of optimized non-conventional derivation approaches is expected to allow the intensification of the production and improvement in the quality of the derived substances. The ability to obtain safe, high-value products is of key importance for potential industrialization.
... This finding suggested the potential of 2 as well as other scalarane-type sesterterpenoids to serve as natural products to manage clinical manifestations caused by the overexpression of CXCL10, such as tumorous diseases (Liu et al., 2011b), autoimmune diseases (Lee et al., 2009), and infectious diseases (Liu et al., 2011a). These scalarane-type sesterpenoids have drawn much attention due to the recent findings as potent anti-inflammatory agents (Peng et al., 2020a;Chakraborty and Francis, 2021;Peng et al., 2021). However, research has been carried out herein to illustrate for the first time the antineurofibroma potential of these sponge-derived scalaranes. ...
Article
Full-text available
In-depth analysis of metabolomics diversity of marine species through advanced mass spectrometric analysis is one of the most promising new tools for the development of marine drugs against mild and life-threatening diseases. Neurofibromas are a common type of tumor in the peripheral nervous system. Currently, there are very limited treatment options for neurofibromas. In our course of exploring potential therapeutic agents for neurofibroma treatment, the multi-informative molecular networking (MIMN) approach was proposed. The MIMNs of the Lendenfeldia sp. sponge extract and sub-fractions were established according to their inhibitory activity against several inflammatory chemokines (CCL3, CCL4, CCL5, CXCL1, CXCL8, and CXCL10) in neurofibroma cell line hTERT-NF1-ipNF95.11b-C (CRL-3390). The visualized MIMN revealed the anti-inflammatory potential of scalarane-enriched fractions, and the follow-up annotation and isolation led to the identification of a scalarane, 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (2). Our results revealed that the most abundant scalarane (2) dominated the anti-chemokine effect of Lendenfeldia sp. extract together with other scalaranes, indicating the potential application of sponge-derived scalaranes to be developed as therapeutic agents for neurofibromas.
Article
Natural products are mainly secondary metabolites produced by plants, microorganisms, and animals, which are still abundant in modern drug discovery. Terpenoids are the most diverse group of natural products, attracting extensive attention owing to their various biological activities. This manuscript reviewed the chemical structures, anti-inflammatory activities, and mechanisms of action of 281 terpenoid natural products reported from 2010 to the present. Their biological targets and both in vitro and in vivo screening models were also surveyed and statistically summarized. This review will provide potential anti-inflammatory lead compounds and helpful information to researchers engaged in natural products and anti-inflammatory drug discovery.
Article
Scalarane‐type sesterterpenoids have received considerable attention in the scientific literature due to their diverse carbon skeletons and various biological activities and pharmacological properties. Among all these derivatives are commonly isolated from marine sponges and are occasionally derived from shell‐less mollusks, such as nudibranchs. This review comprehensively discusses the marine‐derived natural sources that give rise to these scalarane‐type sesterterpenoids, providing the names, their chemical structures, biological properties, with emphasis on anticancer activity and literature references related to these metabolites. A critical summary of the 231 compounds generated from January 2010 up to December 2021 for their potential as anticancer agents is presented.
Article
Two undescribed polyketide type compounds, thalysiaketide A and thalysiaketide B were isolated from a sponge of marine origin Clathria (Thalysias) vulpina (Lamarck, 1814). Thalysiaketide A exhibited significantly greater inhibitory potential against inflammatory 5-lipoxygenase (IC50 0.87 mM) and cyclooxygense-2 (IC50 0.93 mM) compared to those revealed by its thalysiaketide B analogue (IC50 ≥ 1.05 mM). The 5-lipoxygenase inhibitory activity of thalysiaketide A was considerably superior to ibuprofen (standard, IC50 > 4 mM). Higher degree of polar belongings (topological polar surface area 93.06) in conjunction with relatively lower docking parameters of thalysiaketide A with the aminoacyl residues of cyclooxygense-2 and 5-lipoxygenase (docking score -12.99 and -12.27 kcal/mol, respectively) recognized its prospective anti-inflammatory potential.
Article
Two pregnane-type of steroid derivatives characterized as 5α-pregna-3β-methyl pent-3-enoate-12β, 16β diol-20-one (clathroid A) and 12β,15β- dihydroxypregna-4,6-diene-3,20-dione (clathroid B) were purified from the crude extract of the marine sponge, Clathria (Thalysias) vulpina (family Microcionidae) by extensive chromatographic fractionation. The spectroscopic methods including nuclear magnetic resonance spectroscopy were employed to characterize the purified clathroids A-B. The studied compounds exhibited duel inhibitory potentials against pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase (median inhibitory concentration, IC50 < 1 mM), whereas the attenuation property of clathroid A against 5-lipoxygenase (IC50 0.85 mM) was greater than the standard anti-inflammatory ibuprofen (IC50 4.51 mM, p < 0.05). Greater selectivity index (anti cyclooxygense-2/anti cyclooxygense-1) of the studied clathroids (> 1) than ibuprofen (0.43) attributed the greater selective attenuation properties towards pro-inflammatory inducible cyclooxygenase-2 than its constitutive isoenzyme cyclooxygenase-1. The antioxidant potentials of clathroid A against 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50 0.80 mM) and diphenyl-1-picrylhydrazyl (IC50 0.83 mM) free radicals were greater than those of clathroid B (IC50 0.86-0.96 mM). The structure-activity analyses showed that the bioactivities of the clathroids were directly related to their electronic parameters coupled with permissible hydrophobic properties. Clathroid A exhibited grater electronic parameter (topological polar surface area tPSA, 83.83) than clathroid B (74.60) and ibuprofen (37.30), which were found to be in agreement with the prospective anti-inflammatory profile of clathroid A. Clathroid A exhibited higher number of hydrogen bonding interactions with 5-lipoxygenase active site and lesser docking values, such as docking score (DS -12.90 kcal mol⁻¹) and inhibition constant (Ki 1.11 nM) than those recorded by clathroid B (DS -10.49 kcal mol⁻¹; Ki 13.88 nM). The molecular binding properties of clathroid A with 5-lipoxidase inferred that its docking score/ binding energy were positively correlated with their in vitro bioactivie potentilas. A putative biosynthetic pathway of the studied clathroids was proposed from a pregnenolone precursor. The present study recognized the potential of clathroid A isolated from C. (Thalysias) vulpina as prospective anti-inflammatory lead that could find its use in medicinal applications.
Article
Full-text available
Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in prostate cancer cells. Initially, heteronemin exhibited potent cytotoxic effect against LNcap and PC3 prostate cancer cells with IC50 1.4 and 2.7 μM after 24 h, respectively. In the xenograft animal model, the tumor size was significantly suppressed to about 51.9% in the heteronemin-treated group in comparison with the control group with no significant difference in the mice body weights. In addition, the results of a cell-free system assay indicated that heteronemin could act as topoisomerase II (topo II) catalytic inhibitor through the elimination of essential enzymatic activity of topoisomerase IIα expression. We found that the use of heteronemin-triggered apoptosis by 20.1⁻68.3%, caused disruption of mitochondrial membrane potential (MMP) by 66.9⁻99.1% and promoted calcium release by 1.8-, 2.0-, and 2.1-fold compared with the control group in a dose-dependent manner, as demonstrated by annexin-V/PI, rhodamine 123 and Fluo-3 staining assays, respectively. Moreover, our findings indicated that the pretreatment of LNcap cells with an inhibitor of protein tyrosine phosphatase (PTPi) diminished growth inhibition, oxidative and Endoplasmic Reticulum (ER) stress, as well as activation of Chop/Hsp70 induced by heteronemin, suggesting PTP activation plays a crucial rule in the cytotoxic activity of heteronemin. Using molecular docking analysis, heteronemin exhibited more binding affinity to the N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. Finally, heteronemin promoted autophagy and apoptosis through the inhibition of Hsp 90 and topo II as well as PTP activation in prostate cancer cells. Taken together, these multiple targets present heteronemin as an interesting candidate for its future development as an antiprostatic agent.
Article
Full-text available
Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.
Article
Full-text available
Two new sesterterpenes analogs, namely, 12-acetoxy,16-epi-hyrtiolide (1) and 12β-acetoxy,16β-methoxy,20α-hydroxy-17-scalaren-19,20-olide (2), containing a scalarane-based framework along with seven previously reported scalarane-type sesterterpenes (3-9) have been isolated from the sponge Hyrtios erectus (order Dictyoceratida) collected from the Red Sea, Egypt. The structures of the isolated compounds were elucidated on the basis of their spectroscopic data and comparison with reported NMR data. Compounds 1-9 exhibited considerable antiproliferative activity against breast adenocarcinoma (MCF-7), colorectal carcinoma (HCT-116) and hepatocellular carcinoma cells (HepG2). Compounds 3, 5 and 9 were selected for subsequent investigations regarding their mechanism of cell death induction (differential apoptosis/necrosis assessment) and their influence on cell cycle distribution.
Article
Full-text available
Intensive chemical investigation of Korean marine sponge Spongia sp. has led to the isolation of two new scalaranes. The planar structures of the new compounds 1 and 2 were determined through 1D and 2D NMR spectral data analysis, while the relative stereochemistry of the compounds was determined based on the analysis of 1H-1H coupling constants and NOESY spectroscopic data. Compounds 1 and 2 did not display any significant biological activities on farnesoid X-activated receptor (FXR) in co-transfection assay.
Article
Full-text available
Two new indole alkaloids, hainanerectamines A (1) and B (2), and one new β-carboline alkaloids, hainanerectamines C (4), along with five known related alkaloids (3, 5-8), have been isolated from the Hainan marine sponge Hyrtios erecta. The structures of new compounds 1, 2 and 4 were determined by detailed analysis of their 1D and 2D NMR spectra and by comparison of their spectroscopic data with those of related model compounds. Compounds 2-4 exhibited moderate inhibitory activity against Aurora A, a member of serine/threonine kinase family involving in the regulation of cell division and a new target in cancer treatment, with IC50 values of 24.5, 13.6, and 18.6 μg/mL, respectively.
Article
Full-text available
In this review we cover the names, structures, and occurrence of all the scalaranes since their discovery in 1972. We have given special attention to the biological properties of these polycyclic terpenoids of exclusive marine ori-gin.
Article
Full-text available
Despite over a century of applying organic synthesis to the search for drugs, we are still far from even a cursory examination of the vast number of possible small molecules that could be created. Indeed, a thorough examination of all 'chemical space' is practically impossible. Given this, what are the best strategies for identifying small molecules that modulate biological targets? And how might such strategies differ, depending on whether the primary goal is to understand biological systems or to develop potential drugs?
Article
Two fourteen-membered macrocyclic pyrone derivatives named as stomopnolides were identified from the organic extract of echinoidea sea urchin Stomopneustes variolaris by extensive chromatographic purification, and were characterised as methyl 10-butyl-4a-methyl-2-oxo-octahydro-2H-cyclodeca[b]pyran-8-carboxylate (stomopnolide A) and methyl 8²-(4a-methyl-10-(10²-methylbutyl)-2-oxo-octahydro-2H-cyclodeca[b]pyran-8-yl)acetate (stomopnolide B) by spectroscopic methods. The macrocyclic pyrone derivative bearing pyran-8-carboxylate moiety (stomopnolide A) exhibited significantly greater antioxidant properties against 2,2-diphenyl-1-picrylhydrazyl (IC50DPPH 1.43 mM) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (IC50ABTS⁺ 1.63 mM) free radicals than stomopnolide B (IC50 > 1.85 mM) and the commercial standard α-tocopherol (IC50 1.51 mM). Stomopnolide A exhibited potential attenuation property against pro-inflammatory 5-lipoxygenase (IC50 2.78 mM) than those exhibited by stomopnolide B (IC50 3.09 mM) and non-steroidal anti-inflammatory drug, ibuprofen (IC50 4.50 mM, p < 0.05), which signified the prospective anti-inflammatory activity of the former. The greater electronic parameters of stomopnolide A, along with greater number of hydrogen bonds and docking score obtained from the molecular docking studies attributed its potential anti-inflammatory activity.
Article
Chromene derivatives with manifold structural framework and pharmacological properties were ubiquitous in the mollusks of marine origin. A previously undescribed 1H-benzochromenone was isolated through bioassay-guided chromatographic purification of the organic extract of the marine gastropod mollusk Chicoreus ramosus. The compound was characterised as 6-(2′,2′-dimethyl)-3′-en-1′-yl-1′-oxy)-3-hydroxy-1H-benzo[c]chromene-2(10aH)-one based on integrated spectroscopic analysis. The antioxidant studies by employing the stable free radicals reported that the antioxidant activity (IC50 1.4–1.6 mM) was comparable to α-tocopherol (IC50 1.4–1.7 mM). The attenuating potential of the studied compound against pro-inflammatory 5-lipoxygenase (IC50 2.12 mM) was significantly greater than that exhibited by anti-inflammatory drug ibuprofen (IC50 4.4 mM), whereas its inhibitory properties against carbolytic α-amylase (IC50 ∼0.72 mM) was comparable with that displayed by acarbose (IC50 0.43 mM). The present study recognised the potential of 1H-benzochromenone derivative isolated from C. ramosus as important pharmaceutical lead with anti-diabetic and anti-inflammatory potentials to reduce the risk of hyperglycaemia and inflammatory pathologies.
Article
The chemical investigation of the methylene chloride fraction of marine sponge Hyrtios erectus led to the isolation of the known oxysterol (2) along with a new alkyl benzoate compound identified by spectroscopic methods (NMR and MS) as 4′-methylheptyl benzoate (1), whilst the n-butanol fraction afforded the known indole 3-carbaldehyde and β-carboline derivatives. Moreover, the hexane fraction was analysed by GC–MS for their fatty acids (FAs). A total of 17 FAs with chain lengths between 14 and 25 carbons were identified. Methyl-branched FAs are predominated suggesting the presence of bacterial symbionts in the H. erectus sponge. Furthermore, compounds 1 and 2 displayed significant cytotoxicity against breast adenocarcinoma (MCF-7) with IC50 values of 2.4 and 3.8 μM, respectively, since compound 2 was also shown to have potent cytotoxic effect against hepatocellular carcinoma cells (HepG 2) with IC50 value of 1.3 μM.
Article
Two new meroterpeno 2H-pyranoids were isolated from the EtOAc:MeOH extract of yellow-foot clam Paphia malabarica. The structures of these newly reported compounds were elucidated based on spectroscopic interpretations. This is the first report of biogenic 2H-pyrans bearing decadienyl and allyloxy-(isopentanyl)-cyclohexene skeletons from marine biota. The extended C18 sesquiterpenoid with prenylated irregular farnesene framework was characterised as 2-((E)-deca-1,8-dien-10-yl)-11,12-dihydro-13-propyl-2H-pyran (1). The compound 2, 1'-((10E)-10-(10-(pentan-4-yl)-cyclohex-4-enyl)-allyloxy)-tetrahydro-2',2'-dimethyl-2H-pyran represents the first example of naturally occurring C21 prenylated bisabolene-type meroterpenoid, whereas tetrahydro-2',2'-dimethyl-2H-pyran remains attached at C-2' position of rearranged bisabolene framework formed by allyloxy linkage. The antioxidant activities (DPPH/ABTS(+)) of 1 and 2 were comparable (IC50 < 1.0 mg/mL) with α-tocopherol. In addition, these compounds exhibited greater activity against cyclooxygenase-2 than COX-1, and the selectivity indices were significantly lesser (~1.1). No significant differences in anti-5-lipoxygenase activity of 1 and 2 (IC50 1.02-1.06 mg/mL) than ibuprofen (IC50 0.93 mg/mL) indicated the potential anti-inflammatory properties of title compounds.
Article
On the basis of chemical and physicochemical evidence, the chemical structure of foliaspongin, an antiinflammatory active principle of the Okinawan marine sponge Phyllospongia foliascens (Pallas), was elucidated as a new scalarane-type bishomosesterterpene (3).
Article
Structures of three new sesterterpenoid antibiotics 2, 3, and 4, isolated from a marine sponge have been determined by spectral analysis and chemical transformations.
Article
Total phenolic content (TPC) and antioxidant activity (AOA) of 50% aqueous methanol extracts of the marine algae, Padina antillarum, Caulerpa racemosa and Kappaphycus alvarezzi were studied. TPC was measured using Folin–Ciocalteu method while 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), ferrous ion chelating (FIC) assay and beta carotene bleaching (BCB) assay were used to study their AOA. P. antillarum was found to have the highest TPC, 2430±208 mg gallic acid equivalents (GAE) per 100 g dried sample and ascorbic acid equivalent antioxidant capacity (AEAC), 1140±85 mg AA/100 g. C. racemosa and K. alvarezzi displayed lower TPC and AEAC. C. racemosa had 144±22 mg GAE/100 g dried sample of TPC and 14.3±2.0 mg AA/100 g of AEAC, while K. alvarezzi had 115±35 mg/100 g dried sample of TPC and 37.8±16.8 mg AA/100 g of AEAC. In addition, P. antillarum displayed the highest reducing power, 15.7±2.6 mg GAE/g and highest chelating ability. C. racemosa and K. alvarezzi exhibited lower reducing power, 0.737±0.423 mg GAE/g and 0.561±0.269 mg GAE/g, and lower chelating ability. However, the AOA of these three seaweeds as assessed by BCB assay were equally high.
Article
Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells are commonly used as a model for assessing the anti-inflammatory or chemopreventive potential of test compounds. Epimuqubilin A, a norsesterterpene peroxide isolated from marine sponge Latrunculia sp., inhibits nitric oxide production in LPS-stimulated RAW 264.7 cells (IC(50) = 7.6 µM). At both the mRNA and protein levels, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are suppressed in a dose-dependent manner. Mitogen-activated protein kinases (MAPKs), one major upstream signaling pathway involved in the transcription of both COX-2 and iNOS, were not affected by treatment of epimuqubilin A. However, the compound blocked the phosphorylation of inhibitor κB (IκB) kinase (IKKβ), resulting in the stabilization of IκBα, and inhibition of NF-κB p65 nuclear translocation and DNA binding. Levels of phosphorylated IKKα were not affected. This is an unique mechanistic relationship that suggests epimuqubilin A warrants further exploration as a potential therapeutic agent.
Article
In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t(1/2)=360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34 h.
Article
Topological polar surface area (TPSA), which makes use of functional group contributions based on a large database of structures, is a convenient measure of the polar surface area that avoids the need to calculate ligand 3D structure or to decide which is the relevant biological conformation or conformations. We demonstrate the utility of TPSA in 2D-QSAR for 14 sets of diverse pharmacological activity data. Even though a large pool of reports showing the importance of the classic 2D descriptors such as calculated logP (ClogP) and calculated molar refractivity (CMR) exists in the 2D-QSAR literature, this is the first report to demonstrate the value of TPSA as a relevant descriptor applicable to a large, structurally and pharmacologically diverse set of classes of compounds. We also address the limitations of applicability of this descriptor for 2D-QSAR analysis. We observed a negative correlation of TPSA with activity data for anticancer alkaloids, MT1 and MT2 agonists, MAO-B and tumor necrosis factor-alpha inhibitors and a positive correlation with inhibitory activity data for telomerase, PDE-5, GSK-3, DNA-PK, aromatase, malaria, trypanosomatids and CB2 agonists.
Article
Two novel sesterterpenes, 1 and 3, containing a scalarane-based framework, have been isolated from the sponge Hyrtios erectus collected in Papua New Guinea. Their structures and relative stereochemistry have been elucidated by analysis of their spectroscopic data.
Article
Scalaradial (SLD), a marine natural product isolated from the sponge (Cacospongia sp., possesses anti-inflammatory properties in vivo and in vitro (Pharmacologist 32: 168, 1990). In this study we characterize its effects against bee venom phospholipase A2 (PLA2; EC 3.1.1.4). SLD is a potent inactivator of bee venom PLA2 with an IC50 value of 0.07 microM. Inactivation of bee venom PLA2 occurred in a time-dependent, irreversible manner. The rate of inactivation followed first-order reaction kinetics and was dependent on the concentration of SLD. Kinetic analysis suggested a two-step mechanism of inactivation: an initial apparent noncovalent binding (Ki = 4.5 x 10(-5) M) followed by covalent modification. The rate of inactivation was reduced markedly in the presence of excess phosphatidylcholine, suggesting that modification of the enzyme occurs at or near the substrate binding site.
Article
Two novel aplysinopsin-type indole alkaloids, 1 and 2, and three known indole alkaloids were isolated from the marine sponge Hyrtios erecta. These compounds exhibited selective inhibitory activity against the neuronal isozyme of nitric oxide synthase (nNOS). Furthermore, new quinolone 7 was also isolated from the same marine sponge. The chemical structures of these new compounds were elucidated on the basis of spectroscopic analysis.
Article
Four new sesterterpenes, namely, (+)-20-formylhyrtiosal (1), (+)-16-O-acetyl-20-formylhyrtiosal (2), 12-alpha-O-acetylhyrtiolide (3), and 5,10-dihydroxyfurospinulosine-1 (4), together with seven known sesterterpenes (5-11) were isolated from the marine sponge Hyrtios erectus collected at Hainan, China. The structures were elucidated on the basis of extensive spectroscopic analysis involving mainly one- and two-dimensional NMR as well as mass spectroscopy.
Article
A new scalarane-type pentacyclic sesterterpene, sesterstatin 6 (6), was isolated in 8.3 × 10-7% yield from the Republic of Maldives marine sponge Hyrtios erecta. The structure was elucidated by analyses of HRMS and high-field 2-D NMR spectra. Sesterstatin 6 showed significant cancer cell growth inhibition against murine P388 lymphocytic leukemia and a series of human tumor cell lines (ED50 0.17 μg/mL, GI50 1.8-8.9 × 10-1 μg/mL) and proved to be the most inhibitory of the series. © 2005 American Chemical Society and American Society of Pharmacognosy.
Article
A new scalarane-type pentacyclic sesterterpene, sesterstatin 7 (1), was isolated from the Red Sea sponge Hyrtios erecta, together with 16-epi-scalarolbutenolide (2), 25-dehydroxy-12-epi-deacetylscalarin (3), 3-acetylsesterstatin 1 (4), and 21-acetoxydeoxyscalarin. The structure of 1 was elucidated by spectroscopic data interpretation. Sesterstatin 7 (1) showed 63% inhibition of Mycobacterium tuberculosis (H(37)Rv) at a concentration of 6.25 microg/mL. Compound 2 displayed moderate inhibitory activity, while 3 and 4 were weakly active against the same biological target.
Cytotoxic activity of alkyl benzoate and fatty acids from the Red Sea sponge Hyrtios erectus
  • U W Hawas
  • Abou El-Kassem
  • L T Abdelfattah
  • M S Elmallah
  • Miy Eid
  • Mag Monier
  • M Marimuthu