海洋异壁放线菌WH1-2216-6产生的多环含特特拉姆酸大环内酰胺

采用紫外跟踪分离和波谱鉴定的方法,从海洋异壁放线菌(Actinoalloteichus cyanogriseus WH1-2216-6)的发酵产物中分离鉴定了6个5,5,6-多环含特特拉姆酸大环内酰胺(PTMs)类天然产物:16-hydroxymaltophilin(1)、dihydromaltophilin(2)、4-deoxydihydromaltophilin(3)、maltophilin(4)、xanthobaccin C(5)和FI-2(6),其中1为新化合物.评价了化合物1~5对人正常肝细胞L-02及人癌细胞A549、MCF-7、Jurkat、BXPC-3、HCT-116、PANC-1和K562的细胞毒活性,结果表明:化合物1~5对上述人癌细胞具有细胞毒活性,其半数抑制浓度(IC50)为0.1~9.7μmol·L-1;新化合物1对L-02的毒性较低,但对Jurkat、HCT-116和BXPC-3的选择指数(SI)分别高达31.5、41.1和52.4.除化合物2和3对A549和MCF-7的肿瘤细胞毒活性外,其余的肿瘤细胞毒活性是首次报道.还测试了化合物1~6的抗烟曲霉活性,发现化合物2和4的活性较好,其最小抑菌浓度(MIC)分别为3.04和6.12μmol·L-1,这是首次发现5,5,6-PTMs类化合物具有抗烟曲霉活性.     

链霉菌CB03234-S中天赐霉素衍生物的发现

天赐霉素是一种蒽醌骈合型烯二炔类化合物,具有显著的抗肿瘤活性.通过在天赐霉素A高产菌株放线菌CB03234-S中异源表达两个细胞色素P450羟化酶基因dynE10和dynOrf19,分离得到三个天赐霉素衍生物1～3.通过一维和二维核磁共振、高分辨质谱和圆二色谱测定了它们的化学结构.天赐霉素H (1)为天赐霉素D的C-9羟基化产物,TNM T1 (2)为一个烯二炔的环化产物, TNM T3 (3)为已知化合物.化合物1对所有四种测试的肿瘤细胞株,如He La细胞、MB49细胞、B16细胞和BIU87细胞均具有较强的抗肿瘤活性.     

多形炭角菌Xylaria polymorpha菌丝发酵的次级代谢产物研究

从多形炭角菌Xylaria polymorpha(Pers.:Fr.)Grer菌丝发酵产物乙酸乙酯部分中分离鉴定了21个化合物,包括2个新的drimane型倍半萜polymorphines A,B(1~2),1个新的phenyloxolane类化合物2-甲基-2-(4-羟甲基苯基)氧杂环戊烷(3)和18个已知化合物4~21.利用NMR和X射线单晶衍射技术对上述化合物结构进行鉴定与确认.化合物2具有一定的乙酰胆碱酯酶及α-葡萄糖苷酶抑制活性.此外,化合物3具有中等的全齿复活线虫Panagrellus redivivus抑制活性,在浓度为2.5 mg/m L时,线虫致死率为59.6%.     

N-[1-(取代苯基)乙基]-2-羟基苯甲酰肼的合成、表征及抑菌活性

依据邻羟基二苯醚及芳香肼类化合物的抗菌特性, 以邻羟苯基为分子核心, 酰肼键为桥基, 设计合成了7种未见报道的N-(取代苯基)乙基-2-羟基苯甲酰肼类化合物. 以水杨酸甲酯为原料, 经肼解反应后与取代苯乙酮缩合, 再与硼氢化钠反应制得目标化合物, 化合物结构经IR, ¹H NMR和元素分析等证实. 抗菌活性测试结果表明, 该类化合物对不同菌株的抑菌活性具有明显的选择性和特异性. 当质量浓度为1×10^-4 g/mL时, 化合物3b和3e对大肠杆菌和白色念珠菌的抑菌率高达100%, 有极强的抑菌活性; 所有化合物对金黄色葡萄球菌的抑菌率均大于70%, 有一定的抑菌活性. 构效关系分析结果表明, 苯基中引入Cl或Br等卤原子能显著增强化合物的抑菌活性, 而引入-NO₂及-CH₃基团则会降低其抑菌活性.     

石斛根中三个新的菲醌类化合物

综合运用多种现代色谱技术对兰科石斛属植物石斛Dendrobium nobile Lindl.根中的化学成分进行了系统的分离纯化,从其根的乙醇提取物中分离得到了phenanobiles A～C (1～3), 6,7-dihydroxy-2-methoxy-1,4-phenanthrenedione (4)和ephemeranthoquinone (5) 5个菲醌类化合物.采用多种波谱技术确定了这些化合物的结构,其中化合物1～3为新的菲醌类化合物.化合物1～5的体外抗肿瘤活性评价结果表明它们对3种肿瘤细胞株(HL-60,A549以及MCF-7)显示出体外生长抑制活性.     

3-氨基-4-氯-1H吲唑衍生物的合成及抗肿瘤活性测定

以2,6-二氯苯腈为起始原料通过5步反应合成了9个具有抗肿瘤活性的吲唑类化合物并对其抗肿瘤活性进行了初步筛选.目标产物结构经~1H-NMR和IR确证,体外细胞实验结果显示化合物2c的抗肿瘤活性最好,对K-562、SMMC7721肿瘤细胞有明显抑制作用.     

放线菌MY02发酵液活性组分的HPLC分离方法研究

放线菌MY02的发酵提取物对黄瓜枯萎病有显著的抑菌活性,由紫外光谱分析结果初步判断其为四烯大环内酯类化合物.采用高效液相色谱法(HPLC)分离其活性组分,通过分析参数的优化,确定了最佳色谱分离条件:Sinochrom ODS-BP柱(300×4.6 mm i.d.,5 μm),流动相为V(甲醇):V(水)=80:20等度洗脱,流速0.4 mL/min,20℃,检测波长304 nm.方法可满足对MY02发酵液活性组分的分离要求.     

新多环特特拉姆酸大环内酰胺3-Hydroxycombamide Ⅰ的发现

从链霉菌S001的重组菌株S001-cbm-OX4-ikaD中分离获得1个新多环特特拉姆酸大环内酰胺(Po TeMs)类化合物3-hydroxycombamide Ⅰ (2),通过一维、二维核磁共振波谱(NMR)和高分辨质谱(HRMS)数据分析确定其化学结构.化合物2的C-3位羟基推测为宿主链霉菌S001所含羟基化酶催化形成.分别采用滤纸片法和噻唑蓝(MTT)比色法测定了化合物2的抗菌和细胞毒活性,结果显示化合物2无明显活性.此外,化合物2在100μmol/L时对鼠伤寒沙门菌Ⅲ型分泌系统(T3SS)无抑制活性.结果显示Po TeMs的C-3位羟基化修饰可能发生在多环体系氧化修饰之后.     

来源湛江红树内生真菌的二氢异香豆素及其抑菌活性

为了研究湛江红树(Rhizophora apiculata)植物内生真菌Fusarium sp.F67和B42的二氢异香豆素类次级代谢产物及其抑菌活性,采用色谱技术对菌株F67和B42的代谢产物进行分离纯化,确认所得化合物的结构为:3,6,8-三羟基-3,4,5,7-四甲基-3,4-二氢异香豆素(sclerotinin A)(1),二氢橘霉素(2)、5-甲基蜂蜜曲菌素(3)、5-羧基蜂蜜曲菌素(4)、4-羟基蜂蜜曲菌素(5)和蜂蜜曲菌素(6),并利用滤纸片琼脂扩散法检测化合物对7种常见致病菌的抑菌活性。在1.0 g/L质量浓度下化合物1~4对受试菌株的抑菌圈范围为5.1~11.0 mm,其中化合物4的抑菌活性相对较强,抑菌谱相对较广,可为挖掘新型抗菌药物的研究提供补充。     

Indoxamycin家族分子的合成研究进展

Indoxamycins A~F是从海洋放线菌中分离得到的一类聚酮化合物,它们均含有空间拥挤的[5,5,6]三环类笼状结构和6个连续的手性中心.前期活性研究表明,indoxamycins A和F对HT-29肿瘤细胞株具有显著的生长抑制活性.该综述总结了Carreira和丁寒锋两个小组在此家族天然产物全合成中取得的进展情况.     

Synthesis and Antibacterial Activity of Oxazolidinone Derivatives Containing Nitro Heteroaromatic Moiety

A series of novel oxazolidinone derivatives containing nitro heteroaromatic moiety was synthesized and characterized by means of ¹H NMR and MS spectra. All target compounds were evaluated for their in vitro antibacterial activities against S.au 29213, methicillin-resistant Staphylococcus aureus(MRSA) and vancomycin-resistant Enterococcus(VRE) by minimum inhibitory concentration(MIC) assay. Most of them exhibited antibacterial activity against S. au 29213, MRSA and VRE. Among them, compounds 10e and 10f displayed better activity than the control.     

Synthesis and Antibacterial Activities of Pyran Annulated Heterocyclic Compounds

Two novel pyran annulated heterocyclic compounds(1 and 2) were synthesized and characterized via IR, 1H NMR and H RMS. The structure of compound 1 was verified by single-crystal X-ray diffraction. The in vitro antibacterial activities of the two compounds against Staphylococcus aureus(S. aureus ATCC 29213), methicillin-resistant S. aureus(MRSA XJ 75302), vancomycin-intermediate S. aureus(Mu50 ATCC 700699), and USA 300(Los Angeles County clone, LAC) were evaluated by observing the minimum inhibitory concentration.     

Chemical constituents,Antibacterial and Acetylcholine esterase inhibitory activity of Cupressus macrocarpa leaves

Abstract

The chemical constituents of Cupressus macrocarpa were investigated. A new neolignan glycoside (1) in addition to nine known compounds were isolated. The acetylcholinesterase (AChE) inhibitory activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) of different fractions and isolates of C. macrocarpa were evaluated. The light petroleum fraction showed the highest activity in both assays with IC₅₀ value of 88.79 µg/ml and 152.58 µg/ml for the AChE inhibitory activity and MRSA antibacterial activities, respectively. Weak to moderate activity were detected for the isolated compounds.     

Spermine increases bactericidal activity of silver-nanoparticles against clinical methicillin-resistant Staphylococcus aureus

Spermine can effectively reinforce the antibacterial activity of AgNPs.     

Bioactives of Microbes Isolated from Western Ghat Belt of Kerala Show β-Lactamase Inhibition along with Wide Spectrum Antimicrobial Activity

The present study describes the exploitation of microbial biodiversity from Western Ghats of Kerala for screening of bioactives having β-lactamase inhibitory activities. A total of 700 pure cultures were isolated and were screened for antibacterial activity against a β-lactam resistant Bacillus cereus strain (PL 10) isolated from the same niche. Bioactive extracts made from 45 isolates showed inhibitory activities against PL 10, of which two strains showed inhibition of extended spectrum β-lactamase (ESBL) producing Klebsiella ESBL1101 and three strains inhibited methicillin-resistant Staphylococcus aureus (MRSA) strain MRSA831. All these five strains showed wide spectrum antimicrobial activity against various fungi and bacteria. These five cultures were identified by 16S rRNA sequencing and biochemical tests and the preliminary characterizations of their bioactive extracts were carried out. This study suggests the potential of bioactives from two inhibitor–producer strains, NII 167 and NII 1054, for being developed as inhibitors against wide spectrum β-lactam resistant strains.     

Phytogrowth-inhibitory and antibacterial activities of 2,5-dihydroxy-1,4-dithiane and its derivatives

2,5-Dihydroxy-1,4-dithiane (I) and its derivatives (II-IV) showed rather marked inhibitory activities on the growth of the roots of two plant species. All compounds tested had phytogrowth-inhibitory activities. These compounds markedly inhibited the growth of the two plant species at the concentration of 1.0 x 10(-3) M. Seeds of Brassica rapa treated with 2,5-dihydroxy-2,5-dimethyl-1,4-dithiane (III) and its diacetate (IV) at the same concentration failed to germinate. Among these compounds, IV showed the most potent inhibitory activity on the two plant species. The radicles of both plant species treated with these compounds at concentrations higher than 1.0 x 10(-4) M showed negative geotropism, even though germination occurred. The compounds except for 2,5-diacetoxy-1,4-dithiane (II) also had antibacterial activities. In particular, III had rather marked antibacterial activity and its minimal inhibitory concentration (MIC) for Staphylococcus aureus IFO-3060 and Escherichia coli IFO-12734 was 4.0 micrograms/ml.     

Phytogrowth-inhibitory and antimicrobial activities of 3,4'-dihydroxy-alpha,beta-diethylstilbene, the isomer of diethylstilbestrol

3,4'-Dihydroxy-alpha,beta-diethylstilbene (I), like diethylstilbestrol (II), showed phytogrowth-inhibitory and antimicrobial activities. First, compound I showed strong growth-inhibitory activity against the roots of two kinds of plants. The inhibitory activity of I was almost equal to that of sodium 2,4-dichlorophenoxyacetate used as a positive control. The phytogrowth-inhibitory activity of I was much higher than that of II. Next, unlike II, I had broad antifungal spectrum against phathogenic fungi. Compound I showed antifungal activity against six kinds of Fusarium oxysporum sp. This compound also had antibacterial activity against pathogenic and plant-pathogenic bacteria. These antibacterial activities of I were as high as those of II, the isomer of I. It should be emphasized that by shifting one of the phenolic hydroxyl groups of II to meta-position, phytogrowth-inhibitory activity was largely increased, while antimicrobial activity was unchanged.     

Synthesis of indole-based oxadiazoles and their interaction with bacterial peptidoglycan and SARS-CoV-2 main protease: In vitro,molecular docking and in silico ADME/Tox study

In the present study, Indole-based-oxadiazole (1A-17A) compounds were successfully synthesized. The structures of all synthesized compounds were fully characterized by different sophisticated spectroscopic techniques such 1H NMR, 13C NMR, and HREI-MS. Further, the synthesized compounds were explored to investigate their broad-spectrum antibacterial and antibiofilm potential against multidrug resistant Pseudomonas aeruginosa (MDR-PA) and methicillin resistant Staphylococcus aureus (MRSA). The compounds possessed a broad spectrum of antibacterial activity having MIC values of values 1–8 mg/ml against the tested microorganisms. Compound A6 and A7 shows maximum antibacterial activity against MDR-PA, whereas A6, A7 and A11 shows highest activity against MRSA. Furthermore, antibiofilm assay shows that A6, A7 and A11 showed maximum inhibition of biofilm formation and it was found that at 4 mg/ml; A6, A7 and A11 inhibit MRSA biofilm formation by 81.1, 77.5 and 75.9%, respectively; whereas in case of P. aeruginosa; A6 and A7 showed maximum biofilm inhibition and inhibit biofilm formation by 81.5 and 73.7%, respectively. Molecular docking study showed that compounds A6, A7, A8, A10, and A11 had high binding affinity to bacterial peptidoglycan, indicating their potential inhibitory activity against tested bacteria, whereas A6 and A11 were found to be the most effective inhibitors of SARS CoV-2 main protease (3CLpro), with a binding affinity of ? 7.78 kcal/mol. Furthermore, SwissADME and pkCSM-pharmacokinetics online tools was applied to calculate the ADME/Tox profile of the synthesized compounds and the toxicity of these chemicals was found to be low. The Lipinski, Veber, Ghose, and Consensus LogP criteria were also used to predict drug-likeness levels of the compounds. Our findings imply that the synthesized compounds could be a useful for the preventing and treating biofilm-related microbial infection as well as SARS-CoV2 infections.     

Inhibitory study of some novel Schiff base derivatives on Staphylococcus aureus by microcalorimetry

The effect of a series of novel Schiff base compounds on Staphylococcus aureus was studied by microcalorimetric method at 37 °C The results showed that all of the organic compounds had the capacity to inhibit the growth of S. aureus in different extent. And the extent and duration of the inhibitory effect on the growth of S. aureus, judged from the rate constant (k), varied with the different structure of the Schiff base compounds. According to the power-time curves, the multiplication rate constant and inhibition ratio were calculated. The growth rate constant of S. aureus (in log phase) in the presence of Schiff base compounds decreased with the increasing of the concentrations of these compounds regularly. The experimental results revealed that the hydrophilicity of Schiff bases had a great influence on their antibacterial activity. Of these Schiff bases, the greater their hydrophilicity, the higher their antibacterial activity. The antibacterial structure-activity relationship (SAR) of Schiff base derivatives was also briefly discussed.     

Diversity oriented design of various benzophenone derivatives and their in vitro antifungal and antibacterial activities

A series of new substituted benzophenone derivatives was designed, synthesized and screened for their antifungal and antibacterial activities. The bioassays indicated that most of the synthesized compounds showed some antifungal activity against the tested phytopathogenic fungi, but lower antibacterial activities towards the five vibrios isolated from marine sources. The preliminary structure activity relationship (SAR) of the compounds was also discussed.