Synthesis,docking, and biological studies of phenanthrene β-diketo acids as novel HIV-1 integrase inhibitors

In the present study we report the synthesis of halogen-substituted phenanthrene β-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6-Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound of the series, inhibiting both 3′-end processing (3′-P) and strand transfer (ST) with IC₅₀ values of 5 and 1.3 μM, respectively. Docking studies revealed two predominant binding modes that were distinct from the binding modes of raltegravir and elvitegravir, and suggest a novel binding region in the IN active site. Moreover, these compounds are predicted not to interact significantly with some of the key amino acids (Q148 and N155) implicated in viral resistance. Therefore, this series of compounds can further be investigated for a possible chemotype to circumvent resistance to clinical HIV-1 IN inhibitors.     

Beilschglabrines A and B: Two new bioactive phenanthrene alkaloids from the stem bark of Beilschmiedia glabra

Two new phenanthrene alkaloids, beilschglabrines A (1) and B (2) were isolated from the stem bark of Beilschmiedia glabra, together with lupeol, taraxerol, and 24-methylenelanosta-7,9-diene-3β-15α-diol. The structures of the isolated compounds were elucidated by extensive spectroscopic data analysis and comparison with respective literature data. The compounds were tested for DPPH radical scavenging, acetylcholinesterase and lipoxygenase inhibitory activities. Compound 1 displayed considerable activity in the acetylcholinesterase (IC₅₀ 50.4 μM), the DPPH radical scavenging (IC₅₀ 115.9 μM) and the lipoxygenase (IC₅₀ 32.8 μM) assays.     

Cholinesterase inhibitory activity of isoquinoline alkaloids from three Cryptocarya species (Lauraceae)

Alzheimer’s disease is the most common form of dementia among older adults. Acetylcholinesterase and butyrylcholinesterase are two enzymes involved in the breaking down of the neurotransmitter acetylcholine. Inhibitors for these enzymes have potential to prolong the availability of acetylcholine. Hence, the search for such inhibitors especially from natural products is needed in developing potential drugs for Alzheimer’s disease. The present study investigates the cholinesterase inhibitory activity of compounds isolated from three Cryptocarya species towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Nine alkaloids were isolated; (+)-nornantenine 1, (−)-desmethylsecoantofine 2, (+)-oridine 3, (+)-laurotetanine 4 from the leaves of Cryptocarya densiflora BI., atherosperminine 5, (+)-N-methylisococlaurine 6, (+)-N-methyllaurotetanine 7 from the bark of Cryptocarya infectoria Miq., 2-methoxyatherosperminine 8 and (+)-reticuline 9 from the bark of Cryptocarya griffithiana Wight. In general, most of the alkaloids showed higher inhibition towards BChE as compared to AChE. The phenanthrene type alkaloid; 2-methoxyatherosperminine 8, exhibited the most potent inhibition against BChE with IC₅₀ value of 3.95 μM. Analysis of the Lineweaver–Burk (LB) plot of BChE activity over a range of substrate concentration suggested that 2-methoxyatherosperminine 8 exhibited mixed-mode inhibition with an inhibition constant (Ki) of 6.72 μM. Molecular docking studies revealed that 2-methoxyatherosperminine 8 docked well at the choline binding site and catalytic triad of hBChE (butyrylcholinesterase from Homo sapiens); hydrogen bonding with Tyr 128 and His 438 residues respectively.     

14C-菲在营养液-火山石-小麦有控系统中的迁移和转化

利用放射性同位素示踪技术研究了¹⁴C标记菲在有控系统中的迁移转化。结果表明,¹⁴C-菲在有控系统中降解较快,施入药品24d后仅有0.32%的¹⁴C-菲存留在植物、营养液和火山石中。植物吸收的¹⁴C放射性大部分被结合到植物组织中,其它¹⁴C主要以菲的极性代谢物形态存在。     

~(14)C-菲在营养液-火山石-小麦有控系统中的迁移和转化

利用放射性同位素示踪技术研究了１４Ｃ标记菲在有控系统中的迁移转化．结果表明,１４Ｃ菲在有控系统中降解较快,施入药品２４ｄ后仅有０．３２％的１４Ｃ－菲存留在植物、营养液和火山石中．植物吸收的１４Ｃ放射性大部分被结合到植物组织中,其它１４Ｃ主要以菲的极性代谢物形态存在．     

Catabolic role of a three-component salicylate oxygenase from Sphingomonas yanoikuyae B1 in polycyclic aromatic hydrocarbon degradation

Sphingomonas yanoikuyae B1 possesses several different multicomponent oxygenases involved in metabolizing aromatic compounds. Six different pairs of genes encoding large and small subunits of oxygenase iron-sulfur protein components have previously been identified in a gene cluster involved in the degradation of both monocyclic and polycyclic aromatic hydrocarbons. Insertional inactivation of one of the oxygenase large subunit genes, bphA1c, results in a mutant strain unable to grow on naphthalene, phenanthrene, or salicylate. The knockout mutant accumulates salicylate from naphthalene and 1-hydroxy-2-naphthoic acid from phenanthrene indicating the loss of salicylate oxygenase activity. Complementation experiments verify that the salicylate oxygenase in S. yanoikuyae B1 is a three-component enzyme consisting of an oxygenase encoded by bphA2cA1c, a ferredoxin encoded by the adjacent bphA3, and a ferredoxin reductase encoded by bphA4 located over 25kb away. Expression of bphA3-bphA2c-bphA1c genes in Escherichia coli demonstrated the ability of salicylate oxygenase to convert salicylate to catechol and 3-, 4-, and 5-methylsalicylate to methylcatechols.     

An unstructured model for studies on phenanthrene bioconversion by filamentous fungus Cunninghamella elegans

An unstructured model for phenanthrene bioconversion by filamentous fungus Cunnighamella elegans in stirred tank batch bioreactors was proposed. It was observed that the process of phenanthrene bioconversion is strictly associated with exponential growth of biomass. Therefore, a Monod-type, with Contois term, unstructured model could be applied to describe the process mathematically. The inhibition of biomass growth due to high concentrations of phenanthrene present in the medium was taken into account in the form of Yerusalimski's uncompetitive inhibition term.     

Phenanthrene stimulates the degradation of pyrene and fluoranthene by <Emphasis Type="Italic">Burkholderia</Emphasis> sp. VUN10013

Pyrene and fluoranthene, when supplied as the sole carbon source, were not degraded by Burkholderia sp. VUN10013. However, when added in a mixture with phenanthrene, both pyrene and fluoranthene were degraded in liquid broth and soil. The amounts of pyrene and fluoranthene in liquid media (initial concentrations of 50 mg l⁻¹ each) decreased to 42.1% and 41.1%, respectively, after 21 days. The amounts of pyrene and fluoranthene in soil (initial concentrations of 75 mg kg⁻¹ dry soil each) decreased to 25.8% and 12.1%, respectively, after 60 days. None of the high molecular weight (HMW) polycylic aromatic hydrocarbons (PAHs) tested adversely affected phenanthrene degradation by this bacterial strain and the amount of phenanthrene decreased rapidly within 3 and 15 days of incubation in liquid broth and soil, respectively. Anthracene also stimulated the degradation of pyrene or fluoranthene by Burkholderia sp. VUN10013, but to a lesser extent than phenanthrene. The extent of anthracene degradation decreased in the presence of these HMW PAHs.     

固定化微生物降解土壤中菲和芘的研究

1　引　　言固定化微生物技术是 2 0世纪 70年代兴起的一种新型生物技术 ,目前已成为国内外学者的研究热点[8] ,现被广泛应用于处理化学工业废水 .其优点是可以大幅度提高参加反应微生物浓度 ;减少活性污泥数量 ;微生物被高分子材料包埋 ,耐环境冲击 ;根据需要选择有效微生物 ,可降低二次污染等特点 ,因而受到越来越多的关注[4,6 ,10 ] .包埋法是固定化技术最为普遍的使用方法 ,包埋载体的选择是固定化微生物的关键 ,理想的载体具有对微生物无毒性 ,传质性能好 ,性质稳定 ,不易被微生物分解 ,强度高寿命长和价格低廉等优点[2 ] .迄今 ,国内…