Rubralactone,Rubralides A,B and C,and Rubramin Produced by Penicillium rubrum

Rubralactone (1), rubralides A, B and C (2–4), rubramin (5), and 2-formyl-3,5-dihydroxy-4-methylbenzoic acid (6), were isolated from Penicillium rubrum, and their structures established by spectroscopic methods including 2D NMR. The effects on plant growth of 1–6 were examined using the lettuce seedling bioassay. Compound 1 promoted root growth. Compounds 2, 3 and 5 inhibited the growth of lettuce seedlings, but 4 and 6 did not have any inhibitory effect on their growth.     

Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido-carborane: synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular uptake

The preparation of boronated triaryl and tetraaryl phosphonium salts of the type [PPh₃CH₂R]Br [R is 4-boronophenyl (1), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (2), 3-boronophenyl (3), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (4), 2-boronophenyl (5), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (6), and closo-1,2-carboran-1-yl (7)] is described. These compounds were prepared by the reaction of triphenylphosphine with benzylic bromides or 1-bromomethyl-closo-1,2-carborane in acetonitrile solution at 85 °C. The zwitterionic nido-7,8-carborane derivative PPh₃CH₂C₂B₉H₁₁ (8) was prepared by treatment of 7 with cesium fluoride in refluxing ethanol. All compounds were fully characterized by multinuclear (¹H, ¹¹B, ¹³C, and ³¹P) 1D- and 2D-NMR spectroscopy, electrospray ionization mass spectrometry, and elemental analysis, and single-crystal X-ray structures were determined for compounds 1, 3, 7, and 8. The cytotoxicities and boron uptake of selected derivatives were investigated in vitro using human glioblastoma (T98G) and canine kidney tubule (MDCK II) cells. The zwitterionic species 8 was found to be the least cytotoxic agent while also delivering the greatest amount of boron to the T98G cells, peaking at 9.15 ± 2.65 μg B/mg protein.     

Novel Mycelial Components,Ganoderic Acid Mg,Mh, Mi,Mj and Mk,from the Fungus Ganoderma lucidum

Five novel C₃₀ triterpenoids, ganoderic acids Mg (10), Mh (11), Mi (12), Mj (13) and Mk (14), were isolated from the mycelial mat of a G. lucidum strain, which produces C₂₇ lucidenic acids in the fruiting body. Their structures were determined by spectroscopic analysis and chemical conversion.     

Hybrid flavan-chalcones, aromatase and lipoxygenase inhibitors, from Desmos cochinchinensis

Hybrid flavan-chalcones, desmosflavans A (1) and B (2), together with three known compounds, cardamonin (3), pinocembrin (4) and chrysin (5), were isolated from leaves of Desmos cochinchinensis. Cardamonin (3) and chrysin (5) exhibited potent antioxidant activity with 15.0 and 12.2 ORAC units. Desmosflavans A (1) and B (2), pinocembrin (4), and chrysin (5) were found to be inhibitors of aromatase with respective IC₅₀ values of 1.8, 3.3, 0.9, and 0.8 μM. Desmosflavan A (1) inhibited lipoxygenase with the IC₅₀ value of 4.4 μM. Desmosflavan A (1) exhibited cytotoxic activity with IC₅₀ values of 0.29–3.75 μg/mL, while desmosflavan B (2) showed IC₅₀ values of 1.71–27.0 μg/mL.     

Description of nine new species of Heliura Butler from South America (Lepidoptera,Erebidae, Arctiinae,Arctiini, Ctenuchina)

Nine new species of the genus Heliura are described from Brazil (H. brasiliana sp. nov., H. olivocolora sp. nov., H. pulcherrima sp. nov., and H. laerteae sp. nov.), Ecuador (H. ecuadoris sp. nov.), Peru (H. flavipennis sp. nov. and H. peruana sp. nov.), and Venezuela (Heliura albiventris sp. nov. and H. juliani sp. nov.). They are illustrated in habitus and genitalia, and their phylogenetic affinities are discussed based on morphological evidence.     

Design,synthesis of novel pyranotriazolopyrimidines and evaluation of their anti-soybean lipoxygenase,anti-xanthine oxidase,and cytotoxic activities

The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes 2a–e has been accomplished by reaction of 2-acetonitrile derivatives 1a–e with hydroxylamine. Cyclocondensation reaction of precursors 2a–e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a–e, 4a–e, and 5a–e, respectively. On the other hand, the reaction of precursors 2a–e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a–e which evolve under reflux of toluene to the new oxadiazoles 7a–e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i) 5a was the most active (IC_50?=_?4.0?μM) and selective against MCF-7 and (ii) 2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC_50?=_?17 and 12?μM, respectively) while 2e is highly selective against OVCAR-3 (IC_50?=_?10?μM).     

DNA sequence-specific ligands: XIV. Synthesis of fluorescent biologically active dimeric bisbenzimidazoles DB(3, 4, 5, 7, 11)

Five fluorescent symmetrical dimeric bisbenzimidazoles DB(n) containing four 2,6-substituted benzimidazole cores and differing in the length of the oligomethylene linker between two bisbenzimidazole rings (n = 3, 4, 5, 7, 11) have been synthesized. The ability of the dimeric bisbenzimidazoles to form complexes with the double-stranded DNA has been shown by spectral methods. Upon binding to the double-stranded DNA, DB(n) are localized in the narrow groove. The data on the inhibition of the DNA methyltransferase Dnmt3a by DB(n) indicate that dimeric bisbenzimidazoles DB(3) and DB(11) site-specifically bind to the oligonucleotide duplex.     

Community Structure,Geochemical Characteristics and Mineralogy of a Hypersaline Microbial Mat,Cabo Rojo,PR

Seasonal variations in precipitation changed the community composition and microbial activity in a hypersaline, tropical microbial mat, in Cabo Rojo, PR. Using a combination of dissection, light, and transmission electron microscopy, terminal restriction fragment length polymorphism (T-RFLP), in situ microelectrode studies, and ³⁵ S isotope incubations, we documented the major differences between wet and dry seasons. During the wet season (precipitation 177 mm), cyanobacterial (green layer) and anoxyphototrophic (pink layer) communities, as well as the black FeS layer were well-developed, and T-RFLP patterns indicated a diverse community. The rate of oxygenic photosynthesis was 49 μ M min ^{? 1} . Aerobic respiration was 29 μ M min ^{? 1} , and sulfate reduction was 264 nmol cm ^{? 3} h ^{? 1} . During the dry season (precipitation 51 mm), cyanobacteria and anoxyphototrophs were less diverse and abundant, and T-RFLP patterns were less complex. The O ₂ production rate was reduced to 9 μ M min ^{? 1} , as was O ₂ consumption (7 μ M min ^{? 1} ) and sulfate reduction (26 nmol cm ^{? 3} h ^{? 1} ). Aragonite, calcite, halite, and quartz were the predominant minerals. Seasonal differences were found in the green and pink layers for both halite and quartz. Gypsum was not observed, likely due to a sample handling artifact. The fluctuations in community composition and metabolic activity, principally reflected in fluctuations in binding and trapping potential of the uppermost mat community, might be responsible for the observed differences in mineralogy.     

New lanostane-type triterpenoids, inonotsutriols D, and E, from Inonotus obliquus

Two new lanostane-type triterpenoids, inonotsutriols D (1) and E (2), were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) Pil. (Japanese name: kabanoanatake; Russian name: chaga). Their structures were determined to be lanost-8-ene-3β,22R,24R-triol (1) and lanost-8-ene-3β,22R,24S-triol (2) on the basis of spectral data, including 2D NMR analysis. In addition, major compounds, inotodiol (3), trametenolic acid (4), 3β-hydroxylanosta-8,24-dien-21-al (5), 21-hydroxylanosterol (6), inonotsuoxide A (7) and inonotsuoxide B (8) were identified, and all compounds, except 2, were evaluated for their cancer cell growth inhibitory activity against P388, HL-60, L1210 and KB cell lines.     

Density functional theory molecular modelling,DNA interactions,antioxidant, antimicrobial,anticancer and biothermodynamic studies of bioactive water soluble mixed ligand complexes

A novel series of bioactive water soluble mixed ligand complexes (1–5) [M^II(L)(phen)AcO]. nH₂O {where M?=?Cu (1) n?=?2; Co (2), Mn (3), Ni (4), n?=?4 and Zn (5) n?=?2} were synthesized from 2-(2-Morpholinoethylimino) methyl)phenol Schiff base ligand (LH), 1, 10-phenanthroline and metal(II) acetate salt in a 1:1:1 stoichiometric ratio and characterized by several spectral techniques. The obtained analytical and spectral data suggest the octahedral geometry around the central metal ion. Density functional theory calculations have been further supportive to explore the optimized structure and chemical reactivity of these complexes from their frontier molecular orbitals. Gel electrophoresis result indicates that complex (1) manifested an excellent DNA cleavage property than others. The observed binding constants with free energy changes by electronic absorption technique and DNA binding affinity values by viscosity measurements for all compounds were found in the following order (1)?>?(2)?>?(4)?>?(5)?>?(3) > (LH). The binding results and thermodynamic parameters are described the intercalation mode. In vitro antioxidant properties disclose that complex (1) divulges high scavenging activity against DPPH^?, ^?OH, O₂^?? NO^?, and Fe³⁺. The antimicrobial reports illustrate that the complexes (1–5) were exhibited well defined inhibitory effect than ligand (LH) against the selected different pathogenic species. The observed percentage growth inhibition against A549, HepG2, MCF-7, and NHDF cell lines suggest that complex (1) has exhibited superior anticancer potency than others. Thus, the complex (1) may contribute as potential anticancer agent due to its unique interaction mode with DNA.GRAPHICAL ABSTRACT

Communicated by Ramaswamy H. Sarma     

New species of Alaus Eschscholtz, 1829 (Coleoptera: Elateridae,Agrypninae, Hemirhipini)

Four new species of Alaus Eschscholtz, 1829 are described: A. cinnamomeus n. sp., A. latlpennls n. sp., A. serlceus n. sp. and A. thoracopunctatus n. sp. Three species removed from Chalcolepldlus Eschscholtz, 1829, are transferred to this genus: A. allcll (Pjatakowa, 1941) n. comb., A. haroldl (Candèze, 1878) n.comb. and A. unlcus (Fleutiaux, 1910) n. comb. The characters of external morphology of these seven species and male and female genitalia, when available, are described and illustrated. An identification key for all species of the genus is included: A. allcll (Pjatakowa, 1941) n. comb., A. calcarlpllosus Casari, 1996, A. cinnamomeus n. sp., A. haroldl (Candèze, 1878) n. comb., A. latlpennls n. sp., A. lusclosus (Hope, 1832), A. melanops Leconte, 1863, A. myops (Fabricius, 1801), A. nobllls Sallé, 1855, A. oculatus (Linnaeus, 1758), A. patrlclus (Candèze, 1857), A. plebejus Candèze, 1874, A. serlceus n. sp., A. thoracopunctatus n. sp., A. tricolor (Olivier, 1790), A. unlcus (Fleutiaux, 1910) n. comb., A. veracruzanus Casari, 1996 and A. zunianus Casey, 1893.     

Earth,Air, Fire,and Water: Elements of Art

Abstract

Shoshana Zuboff. In the Age of the Smart Machine: The Future of Work and Power. New York: Basic Books, 1988, 468 pp. $11.95 paperback.

George Gilder. Microcosm: The Quantum Revolution in Economics and Technology. New York: Simon &; Schuster, 1989. 426 pp. $19.95 hardcover.

Loren Baritz. The Good Life. New York: Alfred A. Knopf, Inc., 1988. 361 pp. $19.95 hardcover.

Miles Orville. The Real Thing: Imitation and Authority in American Culture, 1880–1940. Chapel Hill: University of North Carolina Press, 1989. 382 pp. $14.95 paperback.

Peter Shaw. The War Against the Intellect. Iowa City: The University of Iowa Press, 1989. 181 pp. $10.95 paperback.

Robert Alter. The Pleasures of Reading in an Ideological Age. New York: Simon &; Schuster, 1989. 250 pp. $18.95 hardcover.

Ian Crofton. A Dictionary of Art Quotations. New York: Macmillan Publishing Company, 1989. $19.95 hardcover.     

Synthesis,Characterization, Cellular Uptake,Apoptosis, Cytotoxicity,Dna-Binding,and Antioxidant Activity Studies of Ruthenium(II) Complexes

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)₂(HECIP)](ClO₄)₂ (1) (HECIP = N-ethyl-4-[(1,10)-phenanthroline(5,6-f)imidazol-2-yl]carbazole, dmb = 4,4’-dimethyl-2,2’-bipyridine) and [Ru(dmp)₂(HECIP)](ClO₄)₂ (2) (dmp = 2,9-dimethyl-1,10-phenanthroline) have been synthesized and characterized. The DNA-binding behaviors of the two complexes were investigated by absorption spectra, viscosity measurements, and photoactivated cleavage. The DNA-binding constants for complexes 1 and 2 were determined to be 8.03 (± 0.12) × 10⁴ M^?1 (s = 1.62) and 2.97 (± 0.15) × 10⁴ M^?1 (s = 1.82), respectively. The results suggest that these complexes interact with DNA through intercalative mode. The photocleavage of pBR322 DNA by Ru(II) complexes was investigated. The cytotoxicity of complexes 1 and 2 has been evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)] method. Complex 1 shows higher anticancer potency than 2 against the four tumor cell lines. Apoptosis and cellular uptake were investigated. The antioxidant activities of the ligand and these complexes were also performed.     

Synthesis,antimicrobial, anti-biofilm evaluation,and molecular modelling study of new chalcone linked amines derivatives

A series of amide chalcones conjugated with different secondary amines were synthesised and characterised by different spectroscopic techniques ¹H NMR, ¹³C NMR, and ESI-MS. They were screened for in vitro antibacterial activity. Compounds 36, 37, 38, 42, and 44 are the most active among the synthesised series exhibiting MIC value of 2.0–10.0?µg/ml against different bacterial strains. Compound 36 was equipotent to the standard drug Ampicillin displaying MBC value of 2.0?µg/ml against the bacterial strain Staphylococcus aureus. The products were screened for anti-biofilm activity. Compounds 36, 37, and 38 exhibited promising anti-biofilm activity with IC₅₀ value ranges from 2.4 to 8.6?µg. Molecular modelling was performed suggesting parameters of signalling anti-biofilm mechanism. AspB327 HisB340 (arene–arene interaction) and IleB328 amino acid residues seemed of higher importance to inhibit c-di-GMP. Hydrophobicity may be crucial for activity. ADME calculations suggested that compounds 36, 37, and 38 could be used as good orally absorbed anti-biofilm agents.     

A Simple Method for Synthesis of Spongosine,Azaspongosine, and Their Antiplatelet Effects

Abstract

Reaction of 2-ethylthioadenine (1) with protected ribose (2) in the presence of stannic chloride gave 2-ethylthioadenosine (4). Oxidation of 5 with potassium permanganate yielded the corresponding sulfone (6) which furnished spongosine (7) after treatment with sodium methoxide. Similarly, reactions of 7-amino-5-ethylthio-1,2,3-triazolo[4,5-d]pyrimidine (8) with the ribose (2) gave 8-azaspongosine (13). The compounds (4) and 7 demonstrated potent antiaggregatory effects both in human platelet-rich plasma and whole blood, whereas, the aza analog (13) showed no inhibitory activity on platelet aggregation. Both (4) and (7) inhibit platelet aggregation in the presence of adenosine deaminase, whereas, adenosine is non-inhibitory, suggesting that analogs (4) and (7) are poor substrates for adenosine deaminase.     

Novel DPPH Radical Scavengers,Demethylbisorbibutenolide and Trichopyrone,from a Fungus

In our screening program for antioxidants with 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging activity, two novel compounds, demethylbisorbibutenolide (1) and trichopyrone (2), were isolated from the fermentation broth of the fungus of USF-4860 strain isolated from a soil sample. The structures of these compounds were determined from spectroscopic evidence. The biosynthetic origin of the carbon atoms of 2 was unambiguously determined by feeding experiments using ¹³C-labeled precursors and elucidation of the ¹³C-NMR spectrum of ¹³C-labeled 2. These studies showed that 2 was derived from five acetates and a methyl group of methionine. In the DPPH-radical scavenging assay, 1 and 2 gave ED₅₀ values of 149 and 167 μM after standing for 2.0 hr. Compound 2 reacted with the DPPH radical to form reaction product 3 which was determined to be 1-[4-(3,4-dihydro-3-methyl-6-{1,3-pentadienyl}-2,4-dioxo-2H-pyran-3-yl)-phenyl]-1-phenyl-2-picrylhydrazine from spectroscopic evidence.     

Desferrithiocin analogue iron chelators: iron clearing efficiency,tissue distribution,and renal toxicity

The current solution to iron-mediated damage in transfusional iron overload disorders is decorporation of excess unmanaged metal, chelation therapy. The clinical development of the tridentate chelator deferitrin (1, Table 1) was halted due to nephrotoxicity. It was then shown by replacing the 4′-(HO) of 1 with a 3,6,9-trioxadecyloxy group, the nephrotoxicity could be ameliorated. Further structure–activity relationship studies have established that the length and the position of the polyether backbone controlled: (1) the ligand’s iron clearing efficiency (ICE), (2) chelator tissue distribution, (3) biliary ferrokinetics, and (4) tissue iron reduction. The current investigation compares the ICE and tissue distribution of a series of (S)-4,5-dihydro-2-[2-hydroxy-4-(polyether)phenyl]-4-methyl-4-thiazolecarboxylic acids (Table 1, 3–5) and the (S)-4,5-dihydro-2-[2-hydroxy-3-(polyether)phenyl]-4-methyl-4-thiazolecarboxylic acids (Table 1, 8–10). The three most effective polyether analogues, in terms of performance ratio (PR), defined as mean ICE_primate/ICE_rodent, are 3 (PR 1.1), 8, (PR 1.5), and 9, now in human trials, (PR 2.2). At the onset of the clinical trial on 9, no data were available for ligand 3 or 8. This is unfortunate, as 3 has many advantages over 9, e.g., the ICE of 3 in rats is 2.5-fold greater than that of 9 and analogue 3 achieves very high levels in the liver, pancreas, and heart, the organs most affected by iron overload. Finally, the impact of 3 on the urinary excretion of kidney injury molecule-1 (Kim-1), an early diagnostic biomarker for monitoring acute kidney toxicity, has been carried out in rats; no evidence of nephrotoxicity was found. Overall, the results suggest that 3 would be a far superior clinical candidate to 9.     

Design and synthesis of antimicrobial,anticoagulant, and anticholinesterase hybrid molecules from 4-methylumbelliferone

We designed and synthesized new series of diverse triazoles, isoxazoles, isoxazolines, and aziridines linked 4-methylumbelliferone 1 using intermolecular 1,3-dipolar cycloaddition reactions. Structures of these compounds were established on the basis of ¹H NMR, ¹³C NMR, and ESI-HRMS. All prepared compounds were evaluated for their antimicrobial, anticoagulant, and anticholinesterase activities. Interestingly, among the tested molecules, some of the analogs displayed better activities than the parent 4-methylumbelliferone 1 such as 6a and 6d for their antifungal properties. Moreover, compounds 4, 5, 6, and 7 showed the importance of the added fragments to 4-methylumbelliferone 1 via the linker methylene to have good activity.     

Synthesis,characterization, antiamoebic activity and cytotoxicity of new pyrazolo[3, 4-d]pyrimidine-6-one derivatives

A new series of pyrazolo[3,4-d]pyrimidine-6-one derivatives (2a–2j) were prepared by using the Biginelli multicomponent cyclocondensation of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (1a), different aromatic aldehydes, and urea with a catalytic amount of HCl at reflux temperature. These compounds were characterized by IR, ¹H NMR, ¹³C NMR, and Mass spectral data. In vitro antiamoebic activity was performed against HM1:IMSS strain of Entamoeba histolytica. The results showed that the compounds 2b, 2i, and 2j with IC₅₀ values of 0.37 µM, 0.04 µM, and 0.06 µM, respectively, exhibited better antiamoebic activity than the standard drug metronidazole (IC₅₀?=?1.33 µM). The toxicological studies of these compounds on human breast cancer MCF-7 cell line showed that the compounds 2b, 2i, and 2j exhibited >80% viability at the concentration range of 1.56–50 µM.