Synthesis,spectral characterization,and in vitro antibacterial and antifungal activities of novel 1,3-thiazine-2-amines comprising morpholine nucleus

A collection of 4-(4-morpholinophenyl)-6-aryl-6H-1,3-thiazin-2-amines (20–28) were synthesized and their in vitro antimicrobial activity was investigated. Compound 21 against P. aeruginosa, 23 against B. subtilis, 24 against V. cholerae and P. aeruginosa, 26 against S. aureus and B. subtilis, 27 against B. subtilis and E. coli, and 28 against all tested bacterial strains exerted excellent antibacterial activity. Compound 20 against A. flavus and Rhizopus, 21, 26 against Rhizopus, 22, 27 against Mucor, 23 against A. flavus, 24 against both A. flavus and Mucor, 25 against all tested strains, and 28 against Rhizopus and M. gypseum exerted excellent antifungal activity.     

Books and the Child

Abstract

Marion Endicott, Emily Carr: The Story of an Artist, Women's Educational Press: Toronto, Canada, 1981, 64 pages, n.p.i. (paperback)

Jean Lipman with Margaret Aspin-wall, Alexander Calder and his Magic Mobiles, Hudson Hills Press: New York, 1981, 96 pages, $15.00

M. B. Goffstein, Lives of the Artists, Farrar, Straus & Giroux: New York, 1982, unpaged, $8.95

Trina Schart Hyman, Self-Portrait, Addison-Wesley: Reading, Massachusetts, 1981, unpaged, $8.95

Andrew Glass, Jackson Makes his Move, Warne: New York, 1982, unpaged, $9.95

Tom Seidmann-Freud, The Magic Boat, Greenwillow: New York, 1981, unpaged, $5.95

Ernest Nister, Magic Windows, Philomel Books: New York, 1980, unpaged, $6.95

Lothar Meggendorfer, The City Park, Viking: New York, 1981, unpaged, $10.95

J. F. Schreiber (verses by Anthea Bell), The Great Menagerie, Viking: New York, 1980, unpaged, $7.95

Lothar Meggendorfer, International Circus, Viking: New York, 1980, unpaged, $7.95

Eric Hill, Spot's First Walk, G. P. Putnam's Sons: New York, 1981, unpaged, $7.95

Robert Crowther and lames R. Diaz (paper engineer), The Most Amazing Hide-and-Seek Counting Book, Viking: New, York, 1981, 14 pages, $8.95

Demi, Where is Willie Worm? Random House: New York, 1981, unpaged, $3.50

John Goodall and Tor Lokvig (paper engineer), PADDY FINDS A JOB, Atheneum: New York, 1981, unpaged, $6.95

Eric Carle, The Honeybee and the Robber, Philomel: New York, 1981, 15 pages, $10.95     

New and little known species of the genus Zorochros Thomson 1859 (Coleoptera: Elateridae) from Palaearctic and Oriental Region

Sixteen new species of the genus Zorochros Thomson 1859 from China, Indonesia, Malaysia, Nepal and Thailand are described and illustrated, a key to the species of the Zorochros indicus group is given, and new records on already known species are provided. New species: Z. ahrensi n. sp., Z bingkorensis n. sp., Z. dabieshanensis n. sp., Z. dolini n. sp., Z. hartmanni n. sp., Z. hubeiensis n. sp., Z. karnaliensis n. sp., Z. magnificus n. sp., Z. naniensis n. sp., Z. nigredos n. sp., Z. platiai n. sp., Z schawalleri n. sp., Z. schmidti n. sp., Z. senaroensis n. sp., Z. theodori n. sp., and Z. tongshanensis n. sp.     

Synthesis and Antimicrobial Activity of Optically Active trans-Cycloheximide Isomers

Optically active tiraras-cycloheximide isomers such as cycloheximide [(2S,4S,6R,αR)-form (1)], naramycin B[(25,4S,6RαR)-form(4)], and new stereoisomers (2S,4S,6S,αS)-form (8) and (2S,4S,6R,αS)-from (9) were synthesized by an aldol condensation of trans-2,4-dimethyl-l-cyclohexanone (5b), with 4-(2-oxoethyl)-2,6-piperidinedione(6). The antimicrobial activity of trans- cycloheximide isomers (1, 4, 8, and 9) was examined against S. cerevisiae and P. oryzae. The stereoisomers 1 and 4 exhibited marked antimicrobial activity against both microorganisms as compared with their C- α-epimers 8 and 9.     

Synthesis,anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA

Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a–7e, 8a–8e, and 9a–9e were designed and synthesised with the aim of evaluating their anti-bacterial and anti-trypanosomal activities and DNA/RNA binding affinity. Results from anti-bacterial evaluations of antibiotic-resistant pathogenic bacteria revealed that both o-chlorophenyl-1,2,3-triazole and N-isopropylamidine moieties in 8c led to strong inhibitory activity against resistant Gram-positive bacteria, particularly the MRSA strain. Furthermore, the non-substituted amidine and phenyl ring in 7a induced a marked anti-bacterial effect, with potency against ESBL-producing Gram-negative E. coli better than those of the antibiotics ceftazidime and ciprofloxacin. UV–Vis and CD spectroscopy, as well as thermal denaturation assays, indicated that compounds 7a and 8c showed also binding affinities towards ctDNA. Anti-trypanosomal evaluations showed that the p-methoxyphenyl-1,2,3-triazole moiety in 7b and 9b enhanced inhibitory activity against T. brucei, with 8b being more potent than nifurtimox, and having minimal toxicity towards mammalian cells.     

Synthesis and Antimicrobial Evaluation of Novel Pyrazolones and Pyrazolone Nucleosides

The synthesis of a novel series of 4-arylhydrazono-5-methyl-1,2-dihydropyrazol-3-ones 4a–h, and their N ²-alkyl and acyclo, glucopyranosyl, and ribofuranosyl derivatives is described. K₂CO₃ catalyzed alkylation of 4a–h with allyl bromide, propargyl bromide, 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide proceeded selectively at the N ²-position of the pyrazolinone ring. Glycosylation of 4a with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose under Vorbruggen glycosylation conditions gave the corresponding N ²-4-arylhydrazonopyrazolone ribofuranoside 9a in good yield. Conventional deprotection of the acetyl protected nucleosides furnished the corresponding 4-arylhydrazonopyrazolone nucleosides in good yields. Selected numbers of the newly synthesized compounds were screened for antimicrobial activity. Compounds 4b, 12a, and 14d showed moderate activities against Aspergillus flavus, Penicillium sp., and Escherichia coli.     

The chemical constituents of Piper kadsura and their cytotoxic and anti-neuroinflammtaory activities

The n-hexane and CHCl₃ soluble fractions of the MeOH extract of the aerial parts of Piper kadsura were found to potently inhibit nitric oxide (NO) production in LPS-activated BV-2 cells, a microglial cell line. From the active fractions, a new stereoisomer of guaiane sesquiterpene, 1α,5β-guai-4(15)-ene-6β,10β-diol, kadsuguain A (1) and a new cyclohexadienone, kadsuketanone A (2), together with twelve known compounds (3–14) were isolated. The structures of these compounds were elucidated by extensive NMR spectral studies. The absolute configuration of 2 was determined by circular dichroism (CD) spectra. Compounds 2, 6, and 11–14 significantly inhibited both nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in the LPS-activated microglia cells. In addition, compounds 4, 6, and 11–14 exhibited cytotoxicity against the A549, SK-OV-3, SK-MEL-2, and HCT15 human tumour cells.     

Books and the Child

Abstract

Jindra Capek (story by Max Bolliger), The Most Beautiful Song, Little, Brown: Boston, 1980, unpaged, $8.95 (boards)

Maurice Sendak, Outside Over There, Harper &; Row: New York, 1981, unpaged, $12.95

Chris van Allsburg, Jumanji, Houghton Mifflin: Boston, Mass., 1981, unpaged, $9.95

Anita Lobel (words by Arnold Lobel), On Market Street, Greenwillow: New York, 1981, unpaged, $8.95

Stephen Gammell (story by Olaf Baker), Where The Buffaloes Begin, Warne: New York, 1981, unpaged, $8.95

Nicola Bayley and William Mayne, The Patchwork Cat, Knopf: New York, 1981, unpaged, $8.95 (boards)

Jan Brett, Fritz and the Beautiful Horses, Houghton Mifflin: Boston, 1981, 32 pages, $8.95

Guy Billout, Thunderbolt and Rainbow: A Look at Greek Mythology, Prentice-Hall: Englewood Cliffs, N.J., 1981, unpaged, $9.95 (boards)

Michael Foreman, Trick a Tracker, Philomel Books: New York, 1981, unpaged, $9.99

Monika Beisner (text by Alison Lurie), Fabulous Beasts, Farrar, Straus &; Giroux: New York, 1981, unpaged, $9.95

Leonard Baskin (words by the Baskin family), Hosie's Zoo, Viking: New York, 1981, unpaged, $10.95     

Organometallic indolo[3,2-c]quinolines versus indolo[3,2-d]benzazepines: synthesis, structural and spectroscopic characterization, and biological efficacy

The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L ¹ ) and N′-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (L ² ) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L ³ ) and N′-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-diamine (L ⁴ ) of the general formulas [(η⁶-p-cymene)M^II(L ¹ )Cl]Cl, where M is Ru (4) and Os (6), [(η⁶-p-cymene)M^II(L ² )Cl]Cl, where M is Ru (5) and Os (7), [(η⁶-p-cymene)M^II(L ³ )Cl]Cl, where M is Ru (8) and Os (10), and [(η⁶-p-cymene)M^II(L ⁴ )Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, spectroscopy (IR, UV–vis, and NMR), and X-ray crystallography (L ¹ ·HCl, 4·H₂O, 5, and 9·2.5H₂O). Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC₅₀ values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L ¹ and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L ⁴ and 11, arguing for additional targets and molecular effects, such as intercalation into DNA.     

Synthesis and Antimicrobial Activity of Chiral cis-Cycloheximide Isomers

Such (+)- and (?)-cis-cycloheximide isomers as isocyclohcximide (1a, 1b), α-epiisocycloheximide (2a, 2b) and neocycloheximide (3a, 3b) were synthesized by aldol condensation of (?)-(2R, 4R)- and (+)-(2S, 4S)-cis-2,4-dimethyl-1-cyclohexanone (5a, 5b). obtained by microbial resolution, with 4-(2-oxoethyl)-2,6-piperidinedione (7). The absolute configuration of the (?)-cis-ketone 5a was confirmed by chemical correlation with natural (2S, 4S, 6S, αR)-cycloheximide (4). The newly synthesized isomer, (?)-α-epiisocycloheximide (2b), showed strong antimicrobial activity against S. cerevisiae andP. oryzae close to that of natural cycloheximide (4).     

Biotransformation of arenobufagin and cinobufotalin by Alternaria alternata

Abstract

The biotransformation of arenobufagin (1) and cinobufotalin (2), isolated from the natural medicine Chan Su, by Alternaria alternata AS 3.4578 was carried out. Incubation of 1 and 2 afforded six metabolites: 3-oxo-arenobufagin (1a), ψ-bufarenogin (1b), 3-oxo-ψ-bufarenogin (1c), 3-oxo-Δ⁴-derivative of cinobufotalin (2a), 3-oxo-cinobufotalin (2b) and 12β-hydroxycinobufotalin (2c). Among them, metabolites 1a, 1c and 2c are new compounds and their structures were characterized on the basis of their spectroscopic data (NMR, MS and IR). Compounds 1, 2, 1b, 2a and 2b were evaluated for their cytotoxicity against HepG2 and MCF-7 human cancer cells, and all of them showed significant inhibitory activities.     

Synthesis and antimicrobial studies of novel 1-benzhydryl-piperazine sulfonamide and carboxamide derivatives

A series of novel substituted 1-benzhydryl-piperazine sulfonamide 8(a–f) and benzamides 9(a–h) were synthesized and their antimicrobial activities evaluated in vitro by paper disc diffusion and micro dilution method against standard strains of Gram-positive (Staphylococcus aureus ATCC 25953, Staphylococcus epidermis 25212, Bacillus cereus 11778, Bacillus substilis 6051) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 2853, Proteus vulgaris ATCC 2853 and Salmonella typhi ATCC 9484) bacteria. Among the synthesized new compounds 8d, 8e, 9c, 9e, 9f and 9 h showed potent antimicrobial activities compared to the standard drug streptomycin.     

Biomineralization of Fungal Hyphae with Calcite (CaCO3) and Calcium Oxalate Mono- and Dihydrate in Carboniferous Limestone Microcosms

The formation of biogenic fabrics in limestone by two fungi, Serpula himantioides and a polymorphic fungal isolate from limestone identified as a Cephalotrichum (syn. Doratomyces) sp., was investigated. The fungal cultures were grown in laboratory microcosms consisting of Carboniferous limestone and after 21 d incubation at 25°C, biomineralization of fungal filaments was observed. Environmental electron scanning microscopy (ESEM) and X-ray micro-analysis (EDXA) of crystalline precipitates on the hyphae of S. himantioides demonstrated that the secondary crystals exhibited different crystalline forms but were similar in elemental composition to the original limestone. Powder X-ray diffraction (XRD) of crystalline precipitates showed they were composed of a mixture of calcite (CaCO ₃ ) and calcium oxalate monohydrate (CaC ₂ O ₄ · H ₂ O). Analysis of crystals precipitated on the hyphae of the limestone isolate, using ESEM and EDXA, showed that the crystals exhibited similar morphological characteristics and elemental composition to the original limestone. XRD showed that they were composed solely of calcite (CaCO ₃ ) or of calcite with some calcium oxalate dihydrate (CaC ₂ O ₄ · 2H ₂ O). These results provide direct experimental evidence for the precipitation of calcite (CaCO ₃ ) and also secondary mycogenic minerals, on fungal hyphae in low nutrient calcareous environments, and suggest that fungi may play a wider role in the biogeochemical carbon cycle than has previously been appreciated.     

The Enantioselective Synthesis of Marmelo Oxides A and B and the Assignment of the Absolute Configurations of Marmelo Oxides

(+)-Marmelo oxide A and (—)-marmelo oxide B were stereoselectively synthesized from d-glutamic acid via (—)-marmelo lactones A and B. The absolute configurations of marmleo oxides were thus determined to be the (+)-oxide A having the (2R, 4R) and (+)-oxide B having (2S, 4R) configurations.     

基本药物制度实施与乡镇卫生院补偿机制转变

目的 了解乡镇卫生院各项收支及药品补偿状况,探讨基本药物制度实施后,取消药品加成对乡镇卫生院的影响。方法 收集华东三省49家乡镇卫生院财务及药品收支数据,对定量资料进行统计分析。结果 乡镇卫生院主要的补偿渠道依然是药品收入,乡镇卫生院收入增长主要归因于增加药品收入。在财政补助收入大幅增加的情况下,乡镇卫生院对药品收入的依赖程度有所降低。结论 基本药物制度的实施对乡镇卫生院的平稳运行有影响,可采取加强财政补助、建立综合补偿机制、遏制药品价格虚高等措施保证乡镇卫生院在改革中的平稳运行。     

武夷菌素高产基因工程菌株Streptomyces albulus OoWysR活性成分的分离鉴定

【背景】武夷菌素高产基因工程菌株Streptomyce albulus OoWysR具有明显的抑菌效果。【目的】明确S.albulus OoWysR的活性成分。【方法】采用柱层析法,利用大孔吸附树脂、离子交换树脂和高效液相色谱等对S.albulus OoWysR的活性成分进行分离纯化,经高分辨率电喷雾电离质谱(high-resolution electrospray ionization mass spectrometry,HR-ESI-MS)和核磁共振(nuclear magnetic resonance,NMR)等波谱技术对化合物化学结构进行鉴定,并通过生长速率法测定化合物的生物活性。【结果】从S.albulus OoWysR中分离鉴定出4个化合物,分别为对羟基苯甲酸(1)、吡咯-2-羧酸(2)、对羟基苯乙醇(3)和云南霉素(4)。化合物1对玉米弯孢病菌、番茄叶霉病菌、玉米小斑病菌和烟草赤星病菌具有一定的抑制作用;化合物2对番茄灰霉病菌、大豆菌核病菌、苹果腐烂病菌、玉米小斑病菌、小麦赤霉病菌、稻瘟病菌和烟草赤星病菌具有一定的抑制作用;化合物3对番茄灰霉病菌、苹果轮纹病菌、玉米小斑病...     

Synthesis and biological evaluation of O-methyl and O-ethyl NSAID hydroxamic acids

This paper reports the synthesis of O-methyl and O-ethyl NSAID hydroxamic acids, their antimicrobial activities, and their ability to inhibit urease and soybean lipoxygenase activities. Ibuprofen and fenoprofen hydroxamic acids with free hydroxy groups present the highest antimicrobial activity, while indomethacin and diclofenac analogs show significantly lower antimicrobial activity. Diclofenac hydroxamic acid 4e exerts the highest anti-urease activity. Indomethacin O-ethyl hydroxamic acid 3h and ibuprofen O-benzyl hydroxamic acid 4b exert significant inhibitory activities on soybean lipoxygenase. Fenoprofen and indomethacin O-ethyl hydroxamic acids 3b and 3h and diclofenac and indomethacin O-benzyl analogs 4g and 4i highly inhibit lipid peroxidation. The highest antioxidant activity was shown by fenoprofen derivative 3b.     

New data and taxa for Orthoptera Tettigoniidae and Acrididae from tropical Africa

The results of a long-term study on the Orthoptera collected in tropical Africa and preserved in different European natural history museums are reported. Horatosphaga bazeletae n. sp. is described from South Africa, Dapanera falxcercata n. sp. from Cameroon, Eurycorypha specularia n. sp. from Zambia (Tettigoniidae Phaneropterinae), and Eucoptacra popovi n. sp. (Acrididae Coptacrinae) from the Gabon. Furthermore, the new genus Pigalua n. gen. is described for Eulioptera insularis Ragge, 1980 from Annobón Is. (Equatorial Guinea). The new tribe Kevaniellini n. trib. is proposed for Kevaniella bipunctata Chopard, 1954. Besides, the hitherto unknown males of Eurycorypha flavescens (Walker, 1869) and Eurycorypha klaptoczi Karny, 1917 from West Africa are described. In addition, new records or unknown taxonomical characters are reported for five species of Horatosphaga, Peronura clavigera Karsch, 1889, Prosphaga splendens Ragge, 1960, Kevaniella bipunctata Chopard, 1954, Eurycorypha prasinata Stål, 1874, Poreuomena lamottei Chopard, 1954, Tylopsis fissa Ragge, 1964, Catoptropteryx extensipes Karsch, 1896 and Mangomaloba latipennis Chopard, 1954 (Tettigoniidae Phaneropterinae).     

Synthesis and Biological Evaluation of 9-(f-2, c-3-Bishydroxymethyl-r-cyclopropylmethyl)-9H-adenine (A Lower Methylene Homolog of Carbocyclic Oxetanocin) and Related Compounds

Abstract

Adenine (7 and 16), thymine (9a and 18a), and 5-fluorouracil (9b and 18b) involving f-2, c-3-bishydroxymethyl-r-1-cyclopropylmethyl- and t-2 t-3-bishydroxymethyl-r-1-cyclopropylmethyl residues were synthesized, starting from trans-1, 4-dibenzyloxy-2-butene and its cis isomer, respectively. These compounds were evaluated for anti HSV-1 activity.