Molecules, Volume 16, Issue 1 (January 2011) – 65 articles , Pages 1-1010

One of the most powerful approaches for the formation of simple and complex chiral molecules is the metal-catalysed asymmetric allylic alkylation. This reaction has been broadly studied with a great variety of substrates and nucleophiles under different reaction conditions and it has promoted the synthesis of new chiral ligands to be evaluated as asymmetric inductors. Although the mechanism as well as the active species equilibria are known, the performance of the catalytic system depends on the fine tuning of factors such as type of substrate, nucleophile nature, reaction medium, catalytic precursor and type of ligand used. Particularly interesting are chiral phosphines which have proved to be effective asymmetric inductors in several such reactions. The present review covers the application of phosphine-donor ligands in Pd-catalysed asymmetric allylic alkylation in the last decade. Full article

The atom-efficiency of one of the most widely used catalytic reactions for forging C-C bonds, the Tsuji-Trost reaction, is limited by the need of preoxidized reagents. This limitation can be overcome by utilization of the recently discovered palladium-catalyzed C-H activation, the allylic C-H alkylation reaction which is the topic of the current review. Particular emphasis is put on current mechanistic proposals for the three reaction types comprising the overall transformation: C-H activation, nucleophillic addition, and re-oxidation of the active catalyst. Recent advances in C-H bond activation are highlighted with emphasis on those leading to C-C bond formation, but where it was deemed necessary for the general understanding of the process closely related C-H oxidations and aminations are also included. It is found that C-H cleavage is most likely achieved by ligand participation which could involve an acetate ion coordinated to Pd. Several of the reported systems rely on benzoquinone for re-oxidation of the active catalyst. The scope for nucleophilic addition in allylic C-H alkylation is currently limited, due to demands on pK_a of the nucleophile. This limitation could be due to the pH dependence of the benzoquinone/hydroquinone redox couple. Alternative methods for re-oxidation that does not rely on benzoquinone could be able to alleviate this limitation. Full article

Bacterial biofilms constitute an extremely resistant form of bacterial colonization with dire health and economical implications. Towards achieving polymeric composites capable of resisting bacterial adhesion and biofilm formation, we prepared five 2,6-pyridinedicarboxylate-based polyesters employing five different diol monomers. The resulting polyesters were complexed with copper (II) or silver (I). The new polymers were characterized by proton and carbon nuclear magnetic resonance spectroscopy, inherent viscosity, infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. The corresponding metal complexes were characterized by differential scanning calorimery and infrared spectroscopy. The amounts of complexed copper and silver were determined by atomic absorption spectrophotometry. Finally, the resulting composites were tested for their antibacterial potential and were found to effectively resist bacterial attachment and growth. Full article

The molecular structures of nine 3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one isomers, obtained by the oxidative cyclization of the corresponding 1-phenylhydrazono chromen-2-ones with copper acetate as catalyst, are reported. The molecular and supramolecular structures of the 8-chloro, 8-bromo- and 8-nitro isomers 2b-d, were established by X-ray diffraction. The halogenated isomers 2b and 2c are isomorphs, they crystallize as a triclinic system, space group P-1 with two molecules in the asymmetric unit. Compound 2d crystallizes as a monoclinic system, space group P2₁/m with two molecules in the unit cell. The 1-phenyl ring [Cg(4)] is almost perpendicularly positioned to the chromene-pyrazole ring system. This conformation is in agreement with the anisotropic NMR shielding effect exerted by the phenyl ring over H-9 in solution. The supramolecular architecture is almost controlled by C―H···A (A = O, p) and face to face p-stacking interactions. The observed p-stacking trend between chromene and pyrazole rings is given by the overlapping between the best donor and acceptor rings in each compound. Full article

We developed a screening procedure to identify ligands from a phage display random peptide library that are selective for circulating bone marrow derived cells homing to angiogenic tumors. Panning the library on blood outgrowth endothelial cell suspension in vitro followed by in vivo selection based on homing of bone marrow-bound phage to angiogenic tumors, yielded the peptide QFPPKLTNNSML. Upon intravenous injection phage displaying this peptide homed to Lewis lung carcinoma (LLC) tumors in vivo whereas control phage did not localize to tumor tissue. Phage carrying the QFPPKLTNNSML peptide labeled with ⁶⁴Cu radionuclide when administered intravenously into a tumor bearing mouse was detected noninvasively with positron emission tomography (PET) around the tumor. These proof-of-principle experiments demonstrate the ability of the QFPPKLTNNSML peptide to deliver payload (radiolabeled phage conjugates) in vivo to sites of ongoing angiogenesis and point to its potential clinical utility in a variety of physiologic and pathologic processes where neovascular growth is a critical component. Full article

Dinophysis spp. blooms and related shellfish toxicity events of diarrhetic shellfish poisoning (DSP) have been the most reported toxicity event through the Croatian National monitoring program. With the aim to characterize the DSP toxin profile in shellfish farmed in Croatia, for the first time a complete analysis of the toxin profile of Croatian mussels has been carried out using the LC-MS/MS technique. The obtained results showed okadaic acid (OA) as the main toxin contaminating Croatian mussels at that time. The maximum concentration of OA in shellfish tissue was recorded 12 days after the Dinophysis fortii bloom, thus suggesting that rapid growth of the toxin level in the shellfish occurred in the first week after the bloom while it was slower in the second week. Furthermore, the presence of only OA at concentrations which could endanger human health suggests D. fortii as the main organism responsible for the toxic event that occurred in Lim Bay. The presence of gymnodimine and spirolides in Croatian mussel has been detected for the first time, while the presence of yessotoxin and pectenotoxin-2 is confirmed. Full article

Ligands selected from phage-displayed random peptide libraries tend to be directed to biologically relevant sites on the surface of the target protein. Consequently, peptides derived from library screenings often modulate the target protein’s activity in vitro and in vivo and can be used as lead compounds in drug design and as alternatives to antibodies for target validation in both genomics and drug discovery. This review discusses the use of phage display to identify membrane receptor modulators with agonistic or antagonistic activities. Because isolating or producing recombinant membrane proteins for use as target molecules in library screening is often impossible, innovative selection strategies such as panning against whole cells or tissues, recombinant receptor ectodomains, or neutralizing antibodies to endogenous binding partners were devised. Prominent examples from a two-decade history of peptide phage display will be presented, focusing on the design of affinity selection experiments, methods for improving the initial hits, and applications of the identified peptides. Full article

This study was to examine the effects of yeast extract (YE) and its fractions (YE1 and YE2) on the growth and diepoxin ζ (a spirobisnaphthalene with a diversity of bioactivities) production in liquid culture of Berkleasmium-like endophytic fungus Dzf12 from Dioscorea zingiberensis. When YE was applied to the liquid medium at 10 g/L on day 3 of culture, the diepoxin ζ production was most effectively enhanced 3.2-fold (378.70 mg/L versus 120.09 mg/L in control) after another 10 days culture. Feeding with 15 g/L of YE on day 9, the mycelia biomass reached 16.44 g/L, about 2.3-fold in comparison with the control (7.15 g/L). The polysaccharide fraction (YE1) was mainly responsible for stimulating diepoxin ζ accumulation, and the non-polysaccharide fraction (YE2) was mainly responsible for promoting mycelia growth. The results showed that the diepoxin ζ production in liquid culture of endophyte Dzf12 could be effectively enhanced by YE and its fractions. Full article

The conventional reaction yield evaluation for radioisotope production is not sufficient to set up the optimal conditions for producing radionuclide products of the desired radiochemical quality. Alternatively, the specific radioactivity (SA) assessment, dealing with the relationship between the affecting factors and the inherent properties of the target and impurities, offers a way to optimally perform the irradiation for production of the best quality radioisotopes for various applications, especially for targeting radiopharmaceutical preparation. Neutron-capture characteristics, target impurity, side nuclear reactions, target burn-up and post-irradiation processing/cooling time are the main parameters affecting the SA of the radioisotope product. These parameters have been incorporated into the format of mathematical equations for the reaction yield and SA assessment. As a method demonstration, the SA assessment of ¹⁷⁷Lu produced based on two different reactions, ¹⁷⁶Lu (n,γ)¹⁷⁷Lu and ¹⁷⁶Yb (n,γ) ¹⁷⁷Yb (β^- decay) ¹⁷⁷Lu, were performed. The irradiation time required for achieving a maximum yield and maximum SA value was evaluated for production based on the ¹⁷⁶Lu (n,γ)¹⁷⁷Lu reaction. The effect of several factors (such as elemental Lu and isotopic impurities) on the ¹⁷⁷Lu SA degradation was evaluated for production based on the ¹⁷⁶Yb (n,γ) ¹⁷⁷Yb (β^- decay) ¹⁷⁷Lu reaction. The method of SA assessment of a mixture of several radioactive sources was developed for the radioisotope produced in a reactor from different targets. Full article

An increasing number of peptides with specific binding affinity to various protein and even non-protein targets are being discovered from phage display libraries. The power of this method lies in its ability to efficiently and rapidly identify ligands with a desired target property from a large population of phage clones displaying diverse surface peptides. However, the search for the needle in the haystack does not always end successfully. False positive results may appear. Thus instead of specific binders phage with no actual affinity toward the target are recovered due to their propagation advantages or binding to other components of the screening system, such as the solid phase, capturing reagents, contaminants in the target sample or blocking agents, rather than the target. Biopanning experiments on different targets performed in our laboratory revealed some previously identified and many new target-unrelated peptide sequences, which have already been frequently described and published, but not yet recognized as target-unrelated. Distinguishing true binders from false positives is an important step toward phage display selections of greater integrity. This article thoroughly reviews and discusses already identified and new target-unrelated peptides and suggests strategies to avoid their isolation. Full article

Using peptides to achieve the functional and structural mimicry of small-molecules, especially those with biological activity or clear biotechnological applications, has great potential in overcoming difficulties associated with synthesis, or unfavorable physical properties. Combinatorial techniques like phage display can aid in the discovery of these peptides even if their mechanism of mimicry is not rationally obvious.The major focus of this field has been limited to developing biotin and sugar mimetics. However, the full “mimicry” of these peptides has not yet been fully established as some bind to the target with a different mechanism than that of the natural ligand and some do not share all of the natural ligand’s binding partners. In this article, mimicry of small-molecules by phage display-discovered peptides is reviewed and their potential in biochemical and medical applications is analyzed. Full article

The in vitro schistosomicidal effects of the essential oil of Ageratum conyzoides L. (Ac-EO) against adult worms of Schistosoma mansoni is reported in this paper. Concerning this activity, Ac-EO was considered to be active, but less effective than the positive control (praziquantel, PZQ) in terms of separation of coupled pairs, mortality, decrease in motor activity, and tegumental alterations. However, Ac-EO caused an interesting dose-dependent reduction in the number of eggs of S. mansoni. Precocene I (74.30%) and (E)-caryophyllene (14.23%) were identified as the two major constituents of Ac-EO. These compounds were tested individually and were found to be much less effective than Ac-EO and PZQ. A mixture of the two major compounds in a ratio similar to that found in the Ac-EO was also less effective than Ac-EO, thus revealing that there are no synergistic effects between these components. These results suggest that the essential oil of A. conyzoides is very promising for the development of new schistosomicidal agents. Full article

In this work we have characterized the action of the naringin, a flavonoid found in grapefruit and known for its various pharmacological effects, which include antioxidant blood lipid lowering and anticancer activity, on the structure and biochemical activities of a secretory phospholipase A (sPLA2) from Crotalus durissus cascavella, an important protein involved in the releasinge of arachidonic acid in phospholipid membranes. sPLA2 was incubated with naringin (mol:mol) at 37 °C and a discrete reduction in the UV scanning signal and a modification of the circular dichroism spectra were observed after treatment with naringin, suggesting modifications of the secondary structure of the protein. This flavonoid was able to decrease enzymatic activity and some pharmacological effects, such as myonecrosis, platelet aggregation, and neurotoxic activity caused by sPLA2, however, the inflammatory effect was not affected by naringin. In addition, small angle X-ray scattering (SAXS) data were collected for sPLA2 and naringin-treated sPLA2 to evaluate possible modifications of the protein structure. These structural investigations have shown that sPLA2 is an elongated dimer in solution and after treatment with naringin a conformational change in the dimeric configuration was observed. Our results suggest that structural modification may be correlated with the loss of enzymatic activity and alterations in pharmacological properties. Full article

Polygonum amplexicaule D. Don var. sinense Forb. (Polygonaceae) (PAF) is a famous traditional herb used to treat fractures, rheumatoid arthritis, muscle injury and pain. The present study was designed to investigate a PAF derived-chemical compound emodin-8-O-β-D-glucoside (EG) on the proliferation and differentiation of osteoblastic MC3T3-E1 cell in vitro. A compound was isolated from PAF extract by HPLC and identified as emodin-8-O-β-D-glucoside (EG) by spectroscopic methods. EG significantly promoted cell proliferation at 0.1–100 ng/mL, and increased the cell proportion in S-phase from 16.34% to 32.16%. Moreover, EG increased alkaline phosphatase (ALP) expression in MC3T3-E1 cells at the concentration from 0.1 to 100 ng/mL and inhibited PGE₂ production induced by TNF-α in osteoblasts at the concentrations ranging from 10–100 ng/mL, suggesting that cell differentiation was induced in MC3T3-E1 osteoblasts. Taken together, these results indicated compound EG directly stimulated cell proliferation and differentiation of osteoblasts, therefore this study preliminarily explored the pharmacological mechanism of PAF to promote the healing of bone rheumatism and various fractures. Full article

Lignin is the second most abundant terrestrial biopolymer after cellulose. It is essential for the viability of vascular plants. Lignin precursors, the monolignols, are synthesized within the cytosol of the cell. Thereafter, these monomeric precursors are exported into the cell wall, where they are polymerized and integrated into the wall matrix. Accordingly, transport of monolignols across cell membranes is a critical step affecting deposition of lignin in the secondarily thickened cell wall. While the biosynthesis of monolignols is relatively well understood, our knowledge of sequestration and transport of these monomers is sketchy. In this article, we review different hypotheses on monolignol transport and summarize the recent progresses toward the understanding of the molecular mechanisms underlying monolignol sequestration and transport across membranes. Deciphering molecular mechanisms for lignin precursor transport will support a better biotechnological solution to manipulate plant lignification for more efficient agricultural and industrial applications of cell wall biomass. Full article

Databases and computational tools for mimotopes have been an important part of phage display study. Five special databases and eighteen algorithms, programs and web servers and their applications are reviewed in this paper. Although these bioinformatics resources have been widely used to exclude target-unrelated peptides, characterize small molecules-protein interactions and map protein-protein interactions, a lot of problems are still waiting to be solved. With the improvement of these tools, they are expected to serve the phage display community better. Full article

Strain DCS523 was isolated from the branch tissue of Daphniphyllum longeracemosum and determined to be a Penicillium sp. according to the ITS sequence analysis. The extracts from the PDA solid fermentation media of Penicillium sp. DCS523 were purified to give two new chroman derivatives as well as six known compounds. Based on their spectral data the new compounds were identified as (Z)-6-acetyl- 3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one (1) and 6-acetyl-2α,5- dihydroxy-2-(2-hydroxypropyl)- 3α,8-dimethylchroman (2), respectively. Full article

The review summarizes data evaluating the role of adenosine receptor signaling in murine hematopoietic functions. The studies carried out utilized either non-selective activation of adenosine receptors induced by elevation of extracellular adenosine or by administration of synthetic adenosine analogs having various proportions of selectivity for a particular receptor. Numerous studies have described stimulatory effects of non-selective activation of adenosine receptors, manifested as enhancement of proliferation of cells at various levels of the hematopoietic hierarchy. Subsequent experimental approaches, considering the hematopoiesis-modulating action of adenosine receptor agonists with a high level of selectivity to individual adenosine receptor subtypes, have revealed differential effects of various adenosine analogs. Whereas selective activation of A₁ receptors has resulted in suppression of proliferation of hematopoietic progenitor and precursor cells, that of A₃ receptors has led to stimulated cell proliferation in these cell compartments. Thus, A₁ and A₃ receptors have been found to play a homeostatic role in suppressed and regenerating hematopoiesis. Selective activation of adenosine A₃ receptors has been found to act curatively under conditions of drug- and radiation-induced myelosuppression. The findings in these and further research areas will be summarized and mechanisms of hematopoiesis-modulating action of adenosine receptor agonists will be discussed. Full article

Tithonia diversifolia is a medicinal plant from the Municipality of Suchiapa, Chiapas, Mexico, that according to local folk medicine is considered useful in the treatment of gastric ulcers. The aim of the present study was to investigate the gastroprotective activity of T. diversifolia by using an ethanol-induced gastric ulcer experimental model in male Wistar rats. The results showed that T. diversifolia had gastroprotective activity, and that the dichloromethane extract had the highest protective activity (close to 90% when using doses between 10 to 100 mg/kg), and that further the compound tagitinin C isolated from this extract was the main active gastroprotective agent. Rats treated with tagitinin C suspended in Tween 80 at 1, 3, 10 and 30 mg/kg showed 37.7, 70.1, 100, and 100% gastroprotection, respectively. The effect elicited by tagitinin C (30 mg/kg) was not attenuated by pretreatment with either N^G-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups, or indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, which suggests that the gastroprotective mechanism of action of this sesquiterpene lactone does not involve NO, sulfhydryl groups or prostaglandins. Full article

The D-, L-enantiomeric pairs of common monosaccharides (xylose, ribose, rhamnose, arabinose, fucose, glucose, mannose, galactose, N-acetylgalactosamine, glucuronic acid and galacturonic acid) were derivatized with 2,3-naphthalenediamine to form the corresponding D-, L-aldo-NAIM derivatives. A simple and facile capillary electrophoretic method was established for sugar composition analysis by simultaneously determining the migration times of these aldo-NAIMs using borate buffer at high pH (100 mM, pH 9.0). The methodology is also applicable to sialic acid (ketose monosaccharides). The quantitation level of the proposed method was in the 10~500 ppm range and the LOD was 1 ppm. The enantioseparation of D, L pairs of aldo-NAIMs were also achieved by using modified sulfated-a-cyclodextrin as the chiral selector in phosphate buffer (300 mM, pH 3.0). In addition, the combination by reductive amination of amino-aldo-NAIM agent and D-, L-enantiomeric pairs of monosaccharides formed a diastereomeric pair for saccharide configuration analysis. Aldo-NAIM derivatives are thus shown to be rapid and efficient agents for analyzing saccharide compositions and configurations with good linearity and short analysis times via capillary electrophoresis. Full article

The novel glycosphingolipid, b-D-GalNAcp(1®4)[a-D-Fucp(1®3)]-b-D-GlcNAcp(1®)Cer (A), isolated from the marine sponge Aplysinella rhax has a unique structure, with D-fucose and N-acetyl-D-galactosamine moieties attached to a reducing-end N-acetyl-D-glucosamine through an a1®3 and b1®4 linkage, respectively. We synthesized glycolipid 1 and some non-natural di- and trisaccharide analogues 2-6 containing a D-fucose residue. Among these compounds, the natural type showed the most potent nitric oxide (NO) production inhibitory activity against LPS-induced J774.1 cells. Our results indicate that both the presence of a D-Fuca1-3GlcNAc-linkage and the ceramide aglycon portion are crucial for optimal NO inhibition. Full article

Carotenoids in the peel and the flesh of persimmon fruit were identified, and the contents of carotenoids in the fleshes of 46 different persimmon cultivars were analyzed. The results indicated that 31 specific carotenoids were detected in both cultivars of persimmons, among which nine specific carotenoids were characterized. β-Cryptoxanthin was the most abundant carotenoid among all individual components in both the peel and the flesh, accounting for about 20-30% of the total carotenoids in both cultivars. The contents of total carotenoids in the fleshes of different persimmon cultivars were between 194.61 µg/100g FW and 1,566.30 µg/100g FW. Zeaxanthin was also the most abundant in all persimmon fleshes besides β-Cryptoxanthin, and the total amount of these two components accounted for 37.84-85.11% of the total carotenoids. The RE values in the fleshes of different cultivars also differed greatly. Besides, the stage of maturation was also important factor which could influence the carotenoid content and RE value in the fleshes. Full article

Enaminone 1 was reacted with hydrazonoyl halides 2a-d to yield 3,4-disubstituted pyrazoles 6a-d. Coupling with arenediazonium chlorides afforded the 2-(arylhydrazono)-3-(1-naphthalenyl)-3-oxopropionaldehydes 13a-c. Compounds 13 could be utilized for the synthesis of a variety of arylpyrazoles, arylazolopyrimidines, and pyridazinones via reaction with hydrazines, aminoazoles, and active methylene derivatives, respectively. A comparative study of aforementioned reactions was carried out with chitosan as a basic ecofriendly catalyst under conventional heating as well as under pressurized microwave irradiation conditions. Full article

The presence of aryl sulfides in biologically active compounds has resulted in the development of new methods to form carbon-sulfur bonds. The synthesis of aryl sulfides via metal catalysis has significantly increased in recent years. Historically, thiolates and sulfides have been thought to plague catalyst activity in the presence of transition metals. Indeed, strong coordination of thiolates and thioethers to transition metals can often hinder catalytic activity; however, various catalysts are able to withstand catalyst deactivation and form aryl carbon-sulfur bonds in high-yielding transformations. This review discusses the metal-catalyzed arylation of thiols and the use of disulfides as metal-thiolate precursors for the formation of C-S bonds. Full article

The methanol and fractionated extracts (hexane, ethyl acetate and water) of Alpinia mutica (Zingiberaceae) rhizomes were investigated for their cytotoxic effect against six human carcinoma cell lines, namely KB, MCF7, A549, Caski, HCT116, HT29 and non-human fibroblast cell line (MRC 5) using an in vitro cytotoxicity assay. The ethyl acetate extract possessed high inhibitory effect against KB, MCF7 and Caski cells (IC₅₀ values of 9.4, 19.7 and 19.8 µg/mL, respectively). Flavokawin B (1), 5,6-dehydrokawain (2), pinostrobin chalcone (3) and alpinetin (4), isolated from the active ethyl acetate extract were also evaluated for their cytotoxic activity. Of these, pinostrobin chalcone (3) and alpinetin (4) were isolated from this plant for the first time. Pinostrobin chalcone (3) displayed very remarkable cytotoxic activity against the tested human cancer cells, such as KB, MCF7 and Caski cells (IC₅₀ values of 6.2, 7.3 and 7.7 µg/mL, respectively). This is the first report of the cytotoxic activity of Alpinia mutica. Full article

The propensity of a half-sandwich (η5-tetramethylcyclopentadienyl) dimethylsilylamido Ti^IV-based catalyst bearing an auxiliary diethylboryl-protected pyridyl moiety (Ti-8), activated by methylaluminoxane (MAO) to homopolymerize α-olefins such as ethylene, 1-hexene and styrene as well as to copolymerize styrene with 1,3-cyclo-hexadiene is described. The reactivity of Ti-8 was investigated in comparison to a 6-(2-(diethylboryl)phenyl)pyrid-2-yl-free analogue (Ti-3). Full article

Thymidine 5´-bis[3-acetyloxy-2-cyano-2-(2-phenylethylcarbamoyl)propyl]phosphate (1) has been prepared and the removal of phosphate protecting groups by hog liver carboxyesterase (HLE) at pH 7.5 and 37 °C has been followed by HPLC. The first detectable intermediates are the (R_P)- and (S_P)-diastereomers of the monodeacetylated triester 14, which subsequently undergo concurrent retro-aldol condensation to diester 4 and enzyme-catalyzed hydrolysis to the fully deacetylated triester 15. The former pathway predominates, representing 90% of the overall breakdown of 14. The diester 4 undergoes the enzymatic deacetylation 700 times less readily than the triester, but gives finally thymidine 5´-monophosphate as the desired main product. To elucidate the potential toxicity of the electrophilic 2-cyano-N-(2-phenylethyl)acrylamideby-product 17 released upon the deprotection, the hydrolysis of 1 has also been studied in the presence of glutathione (GSH). Full article

Six pimarane-type diterpenes isolated from Viguiera arenaria Baker and two semi-synthetic derivatives were evaluated in vitro against a panel of representative microorganisms responsible for dental root canal infections. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia, Prevotella buccae, Fusobacterium nucleatum, Bacteroides fragilis, Actinomyces naeslundii, Actinomyces viscosus, Peptostreptococcus micros, Enterococcus faecalis and Aggregatibacter actinomycetemcomitans. The compounds ent-pimara-8(14),15-dien-19-oic acid, its sodium salt and ent-8(14),15-pimaradien-3β-ol were the most active, displaying MIC values ranging from 1 to 10 μg mL^-1. The results also allow us to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to the discovery of new chemicals for use as a complement to instrumental endodontic procedures. Full article

White spot syndrome virus (WSSV) is the causative agent of white spot syndrome, one of the most devastating diseases in shrimp aquaculture. The genome of WSSV includes a gene that encodes a putative family B DNA polymerase (ORF514), which is 16% identical in amino acid sequence to the Herpes virus 1 DNA polymerase. The aim of this work was to demonstrate the activity of the WSSV ORF514-encoded protein as a DNA polymerase and hence a putative antiviral target. A 3.5 kbp fragment encoding the conserved polymerase and exonuclease domains of ORF514 was overexpressed in bacteria. The recombinant protein showed polymerase activity but with very low level of processivity. Molecular modeling of the catalytic protein core encoded in ORF514 revealed a canonical polymerase fold. Amino acid sequence alignments of ORF514 indicate the presence of a putative PIP box, suggesting that the encoded putative DNA polymerase may use a host processivity factor for optimal activity. We postulate that WSSV ORF514 encodes a bona fide DNA polymerase that requires accessory proteins for activity and maybe target for drugs or compounds that inhibit viral DNA replication. Full article

A chalcone was prepared by the reaction of terephthalaldehyde with 3-acetyl-2,5-dimethylthiophene. Treatment of this chalcone with thiosemicarbazide/phenyl hydrazine/guanidine hydrochloride/thiourea afforded the corresponding pyrazoline, pyrazole, and pyrimidine in good yields. All the new compounds have been characterized by IR, ¹H-NMR, ¹³C-NMR, GC-MS and elemental analyses. The anti-bacterial activity of these compounds were first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined with the reference of standard drug chloramphenicol. The results showed that the pyrazoline derivative is better at inhibiting growth of both types of bacteria (Gram-positive and Gram-negative) compared to chloramphenicol. Full article