In-vitro and in-silico anti-HSV-1 activity of a marine steroid from the jellyfish Cassiopea andromeda venom.

In this study, we investigated the potential in vitro anti-HSV-1 activities of the Cassiopea andromeda jellyfish tentacle extract (TE) and its fractions, as well as computational work on the thymidine kinase (TK) inhibitory activity of the identified secondary metabolites. The LD50, secondary metabolite identification, preparative and analytical chromatography, and in silico TK assessment were performed using the Spearman-Karber, GC-MS, silica gel column chromatography, RP-HPLC, LC-MS, and docking methods, respectively. The antiviral activity of TE and the two purified compounds Ca2 and Ca7 against HSV-1 in Vero cells was evaluated by MTT and RT-PCR assays. The LD50 (IV, mouse) values of TE, Ca2, and Ca7 were 104.0 ± 4, 5120 ± 14, and 197.0 ± 7 (µg/kg), respectively. They exhibited extremely effective antiviral activity against HSV-1. The CC50 and MNTD of TE, Ca2, and Ca7 were (125, 62.5), (25, 12.5), and (50, 3.125) µg/ml, respectively. GC-MS analysis of the tentacle extract revealed seven structurally distinct chemical compositions. Four of the seven compounds had a steroid structure. According to the docking results, all compounds showed binding affinity to the active sites of both thymidine kinase chains. Among them, the steroid compound Pregn-5-ene-3,11-dione, 17,20:20,21 bis [methylenebis(oxy)]-, cyclic 3-(1,2-ethane diyl acetal) (Ca2) exhibited the highest affinity for both enzyme chains, surpassing that of standard acyclovir. In silico data confirmed the experimental results. We conclude that the oxosteroid Ca2 may act as a potent agent against HSV-1.

Chemical contents and toxicity of cigarette butts leachates in aquatic environment: A case study from the Persian Gulf region.

Cigarette butts (CBs) are one of the most commonly found types of litter contaminating the aquatic environment. However, the environmental risks posed by CBs need further investigation. In this study, the in-vivo toxic effects of various concentrations of CB leachates on juvenile (5.45 ± 1.36 gr and 7.08 ± 1.12 cm) fish (Periophthalmus waltoni) were evaluated. The LC50 values of CB leachate from smoked cigarette butts with tobacco (SCB) were 3.75, 3.0, 1.94, and 1.37 CBs/L in 24, 48, 72, and 96 h exposure times, respectively. The LC50 values for leachate of smoked CBs without tobacco (SF) were 7.58, 6.22, 4.73, and 2.9 CBs/L at 24, 48, 72, and 96 h exposure times, respectively. In the case of leachate from unsmoked filters (USF), LC50 values were 14.68, 12.44, 10.19, and 7.46 CBs/L in 24, 48, 72, and 96 h exposure time, respectively. The mean concentrations of heavy metals and polycyclic aromatic hydrocarbons in SCBs leachates were higher than in SF and USF leachates. Our findings report that even low concentrations of CBs leachates can led to lethality of P. waltoni and may pose a threat to their population density.

Oxidative degradation of sulfamethoxazole from secondary treated effluent by ferrate(VI): kinetics, by-products, degradation pathway and toxicity assessment.

Sulfamethoxazole (SMX) is a typical antibiotic in the world, which is frequently detected in the aquatic environment. The current study was aimed to investigate the SMX degradation in secondary treated wastewater using potassium Ferrate [Fe(VI)]. The effects of various experimental conditions, EDTA and phosphate as chelating agents, and toxicity assessment were also considered. Secondary treated effluent was spiked with predefined SMX concentrations, and after desired reaction time with Fe(VI), residual SMX was measured using HPLC. Results indicated that SMX degradation by Fe(VI) was favored under acidic condition, where 90% of SMX degradation was achieved after 120 min. Fe(VI) and SMX reaction obeyed first-order kinetic; meantime, the SMX degradation rate under pH 3 was 7.6 times higher than pH 7. The presence of phosphate (Na2HPO4) and EDTA declined SMX degradation, while Fe (III) effect was contradictory. In addition to promising demolition, 10% TOC removal was achieved. Eighteen major intermediates were identified using LC-MS/MS and the degradation pathways were suggested. Transformation products (TPs) were formed due to hydroxylation, bond cleavage, transformation after bond cleavage, and oxidation reactions. The ECOSAR analysis showed that some of the SMX oxidation products were toxic to aquatic organisms (fish, daphnia and green algae). Supplementary Information: The online version contains supplementary material available at 10.1007/s40201-021-00769-9.

The methanol extract of red algae, Dichotomaria obtusata, from Persian Gulf promotes in vitro osteogenic differentiation of bone marrow mesenchymal stem cells; a biological and phytochemical study.

OBJECTIVES: Osteoporosis is a major public health problem that is appeared with increasing age. This study evaluated the effect of the algae Dichotomaria obtusata methanol extract on osteogenic differentiation of the cultured bone marrow mesenchymal stem cells (BMMSCs) in vitro and analyzed the algae methanol extract to find out the potent beneficial components. METHODS: Dichotomaria obtusata were collected from the coastal area of Bushehr City in the Persian Gulf, Iran. The expression of osteogenesis-related genes was examined using real-time PCR. The formation of calcium deposits in differentiated MSCs was examined by Alizarin R staining. Analyses of algae extract ingredients were performed by gas chromatography-mass spectrometry (GC-MS). KEY FINDINGS: Methanol extract of the algae caused the up-regulation of osteogenic genes that were significant for Osteopontin and Osteocalcin (P < 0.05) and also led to an increase in calcium deposits and matrix mineralization in BMMSCs. The GC-MS analyses of the algae extracts resulted in the identification of steroids and essential fatty acids. CONCLUSION: The results of the study indicated that the methanol extract of D. obtusata may possess significant potentials for the prevention of osteoporosis in vitro.

Studies on the cholinesterases inhibiting compounds from the Cassiopea andromeda venom.

Cholinesterase inhibitors find application in the combat and care of several diseases, especially AD. Jellyfish venoms are the most promising sources of potent cholinesterase inhibitors. Therefore, it is of interest to study cholinesterases inhibiting compounds from the Cassiopea andromeda venom. We report bioactive compounds using the GC-MC method followed by molecular modeling and docking data analysis. The GC-MS analysis of the crude venom led to the identification of seven bioactive compounds (C1-C7), comprising the steroidal alkaloids, phenolic and carotenoid derivatives. The venom exhibited inhibitory activities against the cholinesterase enzymes. The compound C2, a Dioxolane steroid, displayed the strongest inhibition on both AChE and BChE activities for further consideration.

Acetylcholinesterase inhibitory activity of a neurosteroidal alkaloid from the upside-down jellyfish Cassiopea andromeda venom

Abstract Natural compounds from marine organisms have been rarely studied for their acetylcholinesterase inhibitory activities. The aim of this study was to isolate novel compounds with antiAChE activity from the venom of upside-down jellyfish Cassiopea andromeda Forskål, 1775. The compounds of the fractionated venom on gel filtration chromatography were identified by analyzing gas chromatography-mass spectroscopy data. The structure of the isolated compound that showed the most potent antiAChE activity in a docking study was elucidated by different spectral data, including 1H NMR and 13C NMR. Three compounds, including a neurosteroidal alkaloid androtoxin B, were identified from two venom fractions. This neurosteroidal alkaloid showed strong acetylcholinesterase inhibitory activity (IC50 2.24 ± 0.1 µM) compared with the reference standard, galantamine. The results obtained by a docking study demonstrated that Androtoxin B had close contact with two of the three amino acid residues of the catalytic triad of acetylcholinesterase gorge and was accommodated within a peripheral hydrophobic pocket composed of numerous aromatic site chains. In conclusion, the isolated neurosteroidal alkaloid from Cassiopea andromeda was a potent antiAChE agent with strong binding to both the catalytic and peripheral sites of acetylcholinesterase that correlated well with the experimental data. Further studies are required to determine whether androtoxin B could be a potential treatment for Alzheimer's disease.

Green synthesis of novel spiro-indenoquinoxaline derivatives and their cholinesterases inhibition activity.

A convenient synthesis of substituted spiroindenoquinoxalines at mild and green conditions was developed. Multicomponent reaction of substituted phenylene diamines, ninhydrin, malononitrile and N,N'-substituted-2-nitroethene-1,1-diamines produced the target compounds. Twelve new spiroindenoquinoxalines were obtained, and their ability in inhibition of acetyl and butyrylcholinesterases were investigated both in vitro and in silico. All compounds showed moderate level activity against both acetyl and butyrylcholinesterases.

Application of PEG-400 as a green biodegradable polymeric medium for the catalyst-free synthesis of spiro-dihydropyridines and their use as acetyl and butyrylcholinesterase inhibitors.

A simple, efficient and green approach for the synthesis of spiro-dihydropyridines derivatives by one-pot multi-component reaction of isatin or acenaphthoquinone derivatives (1 equiv) with malononitrile (1 equiv) and N,N'-substituted-2-nitroethene-1,1-diamines (1 equiv) in PEG-400 under catalyst-free conditions is described. This method provides several advantages such as environmental friendliness, short reaction time, and simple workup procedure for the synthesis of biologically important compounds. The ability of synthesized compounds in inhibition of acetyl and butyrylcholinesterase were investigated both in vitro and in silico. All compounds showed moderate to high level activity against both acetyl and butyrylcholinesterase. There was a good correlation between in vitro and in silico studies.

Heavy metals' concentration in sediment, shrimp and two fish species from the northwest Persian Gulf.

The concentrations of heavy metals (cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn)) were measured in hepatopancreas and muscle of a commercial shrimp (Metapenaeus affinis), in the muscle, liver and gills of two fish species (Thryssa vitrirostris and Johnius belangerii) and in the sediment samples taken from the mouth of the Arvand river, Meleh estuary and Musa estuary in the northeast Persian Gulf. Concentration of heavy metals varied depending on different tissues, species and sampling sites. Liver of fish and hepatopancreas of shrimp exhibited higher metals' concentration than the other tissues. Generally, in the mouth of the Arvand river, the highest concentration of metals was found in benthic species; while in the mouth of Musa estuary, the highest level of the metals was found in pelagic fish species. Bioaccumulation factors were observed to follow the order: J. belangerii-liver-Cd > T. vitrirostris-liver-Pb > M. affinis-hepatopancreas-Zn >M. affinis-hepatopancreas-Cu >M. affinis- hepatopancreas-Ni. The analysed heavy metals were found in sediment samples at mean concentration in the sediment quality guideline proposed by National Oceanic and Atmospheric Administration (NOAA) and Regional Organization for the Protection of The Marine Environment (ROPME), except for Ni concentration in some cases.

Sulfur-nanoparticle-based method for separation and preconcentration of some heavy metals in marine samples prior to flame atomic absorption spectrometry determination.

The application of sulfur-nanoparticle-loaded alumina as an efficient adsorbent for the solid-phase extraction (SPE) and determination of trace amounts of Cd, Cu, Zn, and Pb ions was investigated in marine samples using flame atomic absorption spectrometry (FAAS). The nanometer-sized sulfur particles were synthesized in situ, physically loaded onto alumina microparticles, and the parameters influencing the preconcentration of the analytes, such as the pH, solution flow rate and volume, eluent solution, and interfering ions, were examined. The results showed that the optimal conditions for quantitative recovery of the metal ions by adsorption and elution on the sulfur nanoparticles (SNPs) was achieved by employing a flow rate of 15 mL min(-1), a pH of 8.5 for the sample solutions, and an eluent composed of 3.0 mol L(-1) HNO(3) in methanol. The detection limits of this method for Cd, Zn, Cu, and Pb ions were 0.30, 0.21, 0.24, and 0.63 µg L(-1) (n=10), respectively. Application of the proposed method to the analysis of fish certified reference material (DORM-3) produced results that were in good agreement with the certified values. The proposed method was also successfully applied to the determination of analytes in marine samples, including seawater, fish, and oysters.