Volume 71, Issue 5-6

In light of the important antitumor activity of acylhydrazone compounds and based on our previous study, 18 new rotundic acid (RA) acylhydrazone derivatives were synthesized. All of the compounds were characterized by their spectroscopic data. The antiproliferative activity of the compounds was evaluated in vitro via the MTT method in three tumor cell lines, including A-375 (human malignant melanoma cells), SPC-A1 (human lung adenocarcinoma) and NCI-H446 (small cell lung cancer). The results showed that the antiproliferative activity of all of the compounds on the NCI-H446 cell line did not increase compared to RA, however, most of the derivatives exhibited higher activity against the A375 and SPC-A1 cell lines as compared to RA. Importantly, the antiproliferative activities of compounds 5a and 5b were the highest among the compounds, with IC 50 values <10 μM. Collectively, compounds 5a and 5b may act as potential anti-tumor agents in the future.

Fifteen N -arylsulfonyl-3-propionylindoles ( 3a–o ) were prepared and preliminarily evaluated as in vitro inhibitors of human immunodeficiency virus type-1 (HIV-1). Three compounds 3c , 3g and 3i exhibited potent anti-HIV-1 activity with effective concentration (EC 50 ) values of 0.8, 4.0 and 1.2 μg/mL, and therapeutic index (TI) values of 11.7, 16.6 and 84.1, respectively. N -( m -Nitro)phenylsulfonyl-3-propionyl-6-methylindole ( 3i ) exhibited the most promising and best activity against HIV-1 replication. The cytotoxicity of these compounds was assessed as well.

A new isomalabaricane-type triterpenoid, jaspiferin G ( 1 ), together with four known isomalabaricane-type triterpenoids, isogeoditin A ( 2 ), 13-( E )-isogeoditin A ( 3 ), jaspolide E ( 4 ), and 22,23-dihydrostellettin D ( 5 ), was isolated from the marine sponge Jaspis stellifera . The structures were elucidated on the basis of spectroscopic data ( 1 H and 13 C NMR, 1 H- 1 H COSY, HSQC, HMBC, and ROESY) and mass spectrometry.

Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro . Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (–logIC 50 = 3.79 ± 0.11 and –logIC 50 = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (–logIC 50 = 4.47 ± 0.12 M) and did not differ from the –logIC 50 value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

Plumbagin, (5-hydroxy-2-methyl-1,4-naphthoquinone), a natural substance found in the roots of plant species in the genus Plumbago , has been used as a traditional medicine against many diseases. In this study, Caenorhabditis elegans was used as a model for testing the anthelmintic effect of plumbagin. The compound exhibited a nematicidal effect against all stages of C. elegans : L4 was least susceptible, while L1 was most susceptible to plumbagin with an LC 50 of 220 and 156 μM, respectively. Plumbagin inhibited C. elegans development from L1 to adult stages with an IC 50 of 235 μM, and body length was also reduced at concentrations of 25 and 50 μg/ml. Brood sizes decreased from 203±6 to 43±6 and 18±3 eggs per hatch in plumbagin-treated worms at 10, 25, 50 μg/ml, respectively. Furthermore, plumbagin was lethal to strains resistant to the nematicides levamisole, albendazole, and ivermectin, indicating that it possesses a strong and unique nematicidal action. Plumbagin decreased the number of mitochondria in hypodermal and intestinal cells and body wall muscles and damaged the ultrastructure of these tissues. Taken together, plumbagin may be a new drug against parasitic nematodes.

Starting from 6-aryl-5-cyano-2-thiouracil derivative 1a–f , a series of novel thiazolo[3,2- a ]pyrimidines 4a–f were synthesized. The mechanism and the regioselectivity of the studied reactions are discussed. In addition, a series of tetrahydro-4- H -pyrimido[2,1- b ][1,3]thiazines 7a–e and 2-((ethoxymethyl)thio)-4-aryl-1,6-dihydropyrimidines 9b,c,e were synthesized. The anti-microbial activities of some of the prepared compounds were screened, and the results revealed that compounds 3c and 4c were more active than the standard ( Ampicillin ) against gram positive bacteria ( Pseudomonas aeruginosa ). Moreover, compounds 4b,e and 3f were found to be good antifungal agents against the studied fungal strains.

Ethanolic and aqueous leaf extracts of Ficus cyathistipula significantly reduced blood-glucose level, improved triglycerides and cholesterol levels of dyslipidemia in diabetic-rats. They similarly reduced the inflammation of paw-edema and stomach-ulcers in rats. Fractions obtained by successive partition of ethanolic extract were assessed for their cytotoxicity, antioxidant and antimicrobial activities; Petroleum ether fraction was the most cytotoxic (IC 50 = 4.43 ± 0.2, 17.3 ± 2.22 and 15.5 ± 3.67 μg/ml on MCF7, HepG2 and HeLa cell lines, respectively). Ethyl acetate fraction was the strongest antioxidant in DPPH assay (IC 50 = 100 μg/ml). All samples exhibited low to strong antimicrobial activity. Chemical investigation of leaf extracts led to the isolation of α-amyrin palmitate (1), lupeol acetate (2), taraxerol (3), β-sitosterol (4), protocatechuic acid (5) and 3- O -caffeoyl quinic acid (6) that were identified via spectral and chromatographic analyses. Metabolite profiling was performed via UPLC-PDA-MS and revealed the presence of flavonoid glycosides, phenolic acids, isoflavones, coumarins and fatty acids. Quantitative determination revealed 593 ± 0.5 mg BSE, 348.1 ± 0.09 mg GAE, 238.7 ± 0.5 mg rutin and 9 ± 0.5 g tannins per 100 g d.wt. of leaves. GLC analysis of lipid fraction revealed identification of phytosterols (15.6%), saturated (51.71%) and unsaturated (41.9%) fatty acids. Galactose, glucose, arabinose and glucoronic acid (36.98%, 28.86%, 22.56% and 1.06%, respectively) were identified by HPLC analysis of mucilage-hydrolysate.

Thymus lanceolatus is a rare species, which grows wild in Algeria and Tunis. It is used traditionally as a drink and to flavor and preserve meat and poultry. The composition of the essential oil was determined by GLC/FID and GLC/MS. Forty-nine components were identified and quantified, accounting for 96.75% of the total detected components in the oil. The oxygenated monoterpenes (74.85%) constitute the major class of volatile secondary metabolites in the oil. Thymol was the most abundant constituent (69.61%) followed by γ -terpinene (8.38%). The antioxidant activity was evaluated using both diphenylpicrylhydrazyl (DPPH˙) reduction and 2-deoxyribose (2-DR) degradation prevention methods. The oil showed a very potent antioxidant activity with IC 50 values of 0.20 ± 0.07 and 4.96 ± 0.39 μg/mL for the DPPH˙ and 2-DR methods, respectively. The antimicrobial activity of the oil was assessed using the agar diffusion method, and the in vitro cytotoxicity on five different cancer cells was examined using the MTT assay. The oil revealed promising inhibitory activity against Gram positive bacteria, especially Bacillus subtilis and Streptococcus pyogenes with an MIC value of 62.5 μg/mL. Additionally, the highest cytotoxic activity was observed against the HL-60 cells with an IC 50 of 113.5 μg/mL. These results validate some of their traditional uses in food preservation.

To explore abundant marine ascidian bioresources, four species from two orders have been compared in their chemical compositions. After a universal separation of the animal body into two fractions, all tunics have been found rich in carbohydrate contents, while all inner body tissues are richer in proteins. Cellulose is present almost exclusively in the tunics and more in the order Stolidobranchia, while more sulfated polysaccharides are present in Phlebobranchia species. Almost all proteins are collagens with a high essential amino acid index and high delicious amino acid (DAA) content. All fractions also have high contents of good-quality fatty acids and trace minerals but low toxic element contents, with different sterols and glycosaminoglycans. There are species-specific characteristics observed for vanadium accumulation and sterol structures which are also meaningful for ascidian chemotaxonomy and resource exploitation. It is suggested that in addition to the present utilizations of tunics for cellulose production and of some species’ inner body tissues as human food, one should explore all species’ inner body tissues as human foods and all tunics as food or animal feed with the contained cellulose as dietary fiber. Collagens, sulfated polysaccharides, glycosaminoglycans, sterols and trace elements could be explored as byproducts for, e.g. pharmaceutical and chemical industries.

Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is the key enzyme to assimilate CO 2 into the biosphere. The nonredundant structural data sets for three RuBisCO domain superfamilies, i.e. large subunit C-terminal domain (LSC), large subunit N-terminal domain (LSN) and small subunit domain (SS), were selected using QR factorization based on the structural alignment with Q H as the similarity measure. The structural phylogenies were then constructed to investigate a possible functional significance of the evolutionary diversification. The LSC could have occurred in both bacteria and archaea, and has evolved towards increased complexity in both bacteria and eukaryotes with a 4-helix–2-helix–2-helix bundle being extended into a 5-helix–3-helix–3-helix one at the LSC carboxyl-terminus. The structural variations of LSN could have originated not only in bacteria with a short coil, but also in eukaryotes with a long one. Meanwhile, the SS dendrogram can be contributed to the structural variations at the βA–βB-loop region. All the structural variations observed in the coil regions have influence on catalytic performance or CO 2 /O 2 selectivities of RuBisCOs from different species. Such findings provide insights on RuBisCO improvements.