青霉属真菌次级代谢产物的结构类型及其药用活性的研究进展

青霉属(Penicillium)真菌属于腐生类真菌,是自然界中一类重要的分解者。其可以产生多种多样的次级代谢产物。这些结构新颖、功能特殊的次级代谢产物在抗菌、抗氧化、抗肿瘤等药物开发中发挥重要作用,主要由聚酮类、生物碱、萜类、大环内酯等化学结构类型组成。本文综述了青霉属真菌次级代谢产物的结构类型以及丰富的生物药用活性,该内容可为后续青霉属真菌新型天然药物的开发提供研究思路。     

药用真菌活性次级代谢产物研究

药用真菌作为我国传统中医药体系的重要组成部分,有着悠久的历史。它们能够产生丰富的活性次级代谢产物,具有神经保护、抗肿瘤、降血脂等诸多药效。然而,目前对大部分药用真菌次级代谢产物的化学和生物学研究较少。本课题组主要以抗肿瘤、抗炎、抗菌以及抗病毒等生物活性为指导,选择重要药用真菌进行化学研究,构建我国特色药用真菌代谢产物库。文章主要介绍近4年我们在这方面的研究进展。     

真菌多糖的活性研究进展

真菌多糖是一类从真菌的子实体或菌丝体分离出来的天然高分子化合物。研究表明,真菌多糖具有抗病毒、抗凝血、降血脂、抗肿瘤、免疫调节、延缓衰老等多种生物活性,现已被开发成多种药物和功能性食品添加剂。随着天然药物化学、药理研究的不断深入,真菌多糖已引起国内外学者的极大兴趣,其重要生物学效应成为当今研究的热点。     

海洋曲霉属真菌抗菌活性物质的研究进展

海洋微生物由于其独特的生存环境造就了许多结构新颖、具有特殊生物活性的代谢产物。随着科学技术的发展,科学界掀起了对海洋微生物代谢物的研究浪潮。近年来的研究表明,海洋曲霉属真菌及其次级代谢产物具有抗肿瘤、抗菌、抗病毒等生物活性。通过查阅文献与资料,对近年来海洋曲霉属真菌及其次级代谢产物的化学结构及生物活性研究与开发的进展进行综述总结,以期有助于后续研究及应用。     

虫草属真菌化学成分及药理作用研究进展

虫草属真菌是一类十分重要的药用真菌,具有多种活性物质及广泛的药理作用、对该属真菌的化学成分及药理作用的研究进展进行了综述,为虫草属药用真菌的研究和开发提供依据。     

Nigrospora 属真菌化学成分及生物活性研究进展CSCD

Nigrospora属真菌是常见的药用动植物内生真菌,其次级代谢产物结构多样且生物活性显著,是药用活性物质的重要来源。本文对1997年至2021年报道的Nigrospora属真菌化学成分及其生物活性首次进行了系统综述,涵盖聚酮、蒽醌、萜、甾体和生物碱等199个化合物,并总结其抗菌、抗氧化、抗病毒、抗糖尿病和抗肿瘤等生物活性,以期为该属真菌药用成分的深度开发提供参考。     

漳江口红树林沉积物真菌多样性分析及抗茶叶致病真菌生物活性筛选

以福建漳江口红树林国家级自然保护区红树林沉积物分离的真菌为对象,研究红树林沉积物真菌的多样性和筛选抗茶叶病原真菌活性的菌株。将分离纯化的135株真菌通过形态学和Ribosomal DNA-Internal Transcribed Spacer(rDNAITS)序列测定进行鉴定及多样性分析,归为40个种类型,分别属于17个属,其中青霉属(25%)为优势菌,木霉属(15%)、曲霉属(10%)和镰刀属(10%)次之,表明红树林沉积物真菌具有丰富的多样性;利用平板对峙法对真菌的发酵粗提物抗茶叶病原真菌生物活性研究,结果发现,共有17株(占42.5%)真菌具有抗茶叶病原真菌活性,其中15株能够抑制茶叶轮斑病(Pestalotiopsis theae)LH13,12株能够抑制茶叶炭疽病(Colletotrichum gloeosporioides)LH30,8株能够抑制茶叶溃疡病(Neofusicoccumsp.)LH107,有两株对这三种茶叶致病菌均有较强活性。这些活性菌株分布在6个属中,分别是青霉属(7株)、木霉属(3株)、镰孢属(2株)、枝孢属(2株)、白地霉属(2株)和球腔菌属(1株)。由此可见,红树林沉积物真菌抗菌活性菌株的种属分布具有多样性。     

栎生桑黄和忍冬桑黄液体培养过程中发酵液抗氧化能力

桑黄孔菌属Sanghuangporus是药用木生真菌资源中一个重要的属,但是该属仅有少数几个种类被用于人工栽培,且栽培面积较小。此外,桑黄孔菌属中大部分种类的药用功能仍未完全明确。因此,本研究以桑黄孔菌属近期新发表的新种栎生桑黄S. quercicola和关注度较低的忍冬桑黄S. lonicericola为主要研究对象,通过测定它们液体培养过程中第2、4、6、8、10、12和14天的菌丝生物量以及发酵液的粗多糖含量、多酚含量、黄酮含量、抗坏血酸含量、DPPH自由基清除能力、ABTS自由基清除能力、总抗氧化能力、超氧化物歧化酶活性、羟自由基清除能力、超氧阴离子清除能力、铁离子还原能力和亚铁离子螯合能力等12个抗氧化指标,对桑黄的抗氧化能力进行评定。2种桑黄真菌各选取一号菌株,其发酵液均表现出强抗氧化能力。相比之下,栎生桑黄的多糖、抗坏血酸和超氧化物歧化酶含量更高,而忍冬桑黄的多酚和黄酮含量更高。相应的,栎生桑黄和忍冬桑黄在其他一些抗氧化指标上也表现出强弱程度及出现时间的差异。上述研究结果为桑黄孔菌属真菌的药用功能开发提供了新资源,为不同抗氧化代谢产物的分离纯化提供了科学依据。     

猴头菌属真菌化学成分及药理活性研究概述

对猴头菌属真菌的小分子化学成分、药理活性等方面的研究进行了综述.小分子化学成分研究结果表明,猴头菌属真菌含有多种萜类、酚类、甾体类、吡喃酮类、脂肪酸类等化学成分;现代医学和药理学的很多研究认为,猴头菌属真菌具有抗肿瘤、提高免疫力、抗溃疡、抗炎症、抗糖尿病、抗氧化、保肝等多种药用功效.文中讨论了目前研究中存在的主要问题并...     

桃儿七和南山荷叶内生真菌的生物活性研究

通过研究桃儿七(Sinopodophyllum hexandrum)与南方山荷叶(Diphylleia sinensis)的内生真菌的生物活性,探讨内生真菌作为生物活性物质资源开发利用的价值。测定内生真菌发酵液的抗细菌、抗真菌、抗卤虫活性后,发现大多数菌株的发酵液都具有不同的生物活性。高活性菌株集中于镰孢霉属、柱孢属、木霉属、色串孢属。桃儿七内生真菌抗真菌活性较强,南方山荷叶内生真菌抗细菌和抗卤虫活性较强。桃儿七和南方山荷叶内生真菌是寻找有价值的活性成分的良好资源。     

Structure-activity relationships of the saponins dioscin and dioscinin

Hemolytic and antifungal activities of partial acid hydrolysates of dioscin and dioscinin were compared. In general, these activities were proportional to the number of sugar residues and those derivatives having branched sugar chains showed higher activities than those with straight chains. The 17-hydroxyl group of the dioscinin derivatives reduced both biological activities.     

Antiinflammatory and antioxidant evaluation of novel coumarin derivatives

Several coumarin derivatives have been reported to present multiple biological activities and especially antiinflammatory/antioxidant activities. Recently the synthesis and in vivo/in vitro anti-inflammatory/antioxidant activities of several new coumarin derivatives with a 7-azomethine linkage have been reported. In the present study these derivatives were further tested for their antioxidant ability. Some of them were found in vitro to inhibit lipid peroxidation and to strongly scavenge superoxide radicals. Compound 3 was found to potently inhibit cyclooxygenase-1 (COX-1) and the yeast-induced rat paw oedema. The most active compounds within the set were tested against adjuvant-induced arthritis. Compound 3 was found to significantly protect the rats from adjuvant-induced arthritis (when it is administered from the first day or when it is administered the fourteenth day, with the first symptoms of the disease). An attempt was made to delineate the possible mechanism of action of the studied compounds.     

Design, synthesis, and biological activity of novel 4-(3,4-dimethoxyphenyl)-2-methylthiazole-5-carboxylic acid derivatives

Novel 4-(3,4-dimethoxyphenyl)-2-methylthiazole-5-carboxylic acid derivatives (11-23) were synthesized from 3,4-dimethoxyacetophenone (5) in six-step procedure. Their biological activities were evaluated in the greenhouse. Some of the compounds had shown fungicidal and insecticidal activities at 375 g ai/ha and 600 g ai/ha, respectively.     

Design,Synthesis and Antitumor Activity of FAK/PLK1 Dual Inhibitors with Quinazolinone as the Skeleton

Febrifugine is a kind of quinazolinone compound with high biological activity from a Chinese herb called Chang Shan (Dichroa febrifuga). Febrifugine and its derivatives possess extensive biological activities, some of which exhibited anti-tumor activities as FAK inhibitors. However, they are not very effective at inhibiting tumor metastasis, perhaps because tumors gain energy through compensatory activation of other signaling pathways that promote cell migration and invasion. Therefore, seventeen novel febrifugine derivatives with quinazolinone skeleton were designed, synthesized and acted as potential FAK/PLK1 dual inhibitors. These compounds were determined by ¹H-NMR, ¹³C-NMR and MS. Most of the compounds exhibited good inhibitory activity against cancer cell lines by computer-assisted screening, antitumor activity test and FAK/PLK1 inhibitory activity test, wherein compound 3b was screened as a high-efficiency lead compound.     

Alkylation reactions of phosphachroman-2,4-diones and 4-hydroxy phosphacoumarins

Phosphachroman-2,4-dione and 4-alkoxyphosphacoumarin derivatives, phosphonic analogues of chromones and coumarins with potential biological activities, were synthesized in good yields through sequential base-catalyzed intramolecular cyclization of O-alkyl-O'-(2'-methoxycarbonyl phenyl)-(substituted) benzyl phosphonates and alkylation. The synthesis sets the stage for an examination of the biological activities.     

Synthesis and biological activity of aminophenylphosphonic derivatives of levorin

Reactions of levorin, a polyenic macrolide antibiotic, with aromatic aldehydes and hypophosphorous acid resulted in formation of its amino phenylphosphonium derivatives. Physicochemical and biological properties of the derivatives were studied. The levorin amino phenylphosphonium derivatives were shown to be low toxic and have antifungal and antiviral activities.     

Trypsin-resistant forms of human growth hormone have diabetogenic and insulin-like activities

Although diabetogenic and insulin-like activities are intrinsic properties of the growth hormone (GH) molecule, it has been frequently suggested that the hormone must be proteolytically processed for these activities to be expressed. If this is correct, then derivatives of GH having resistance to appropriate proteolytic attack might not have diabetogenic and/or insulin-like activity. The purpose of the present study was to prepare derivatives of human GH that are resistant to digestion by trypsin and to determine whether they possess diabetogenic or insulin-like activity. Three derivatives were prepared from purified native human GH in which lysine residues were modified with methyl acetimidate, citraconic anhydride or S-ethyl-thioltrifluoroacetate, and one in which arginine residues were modified with camphorquinone-10-sulfonic acid. Comparisons of peptide maps of tryptic digests of these derivatives with that of unmodified human GH indicated that all four were resistant to proteolysis by trypsin. All of these trypsin-resistant forms of human GH were found to possess significant growth-promoting, diabetogenic and insulin-like activities, although all activities were attenuated to some extent in each derivative. The relative potencies of the human GH derivatives in a radioimmunoassay for human GH were somewhat similar to their order of potency in the growth-promoting and diabetogenic assays. These results suggest that if proteolytic processing of the GH molecule is involved in the expression of one or more of its biological activities, such processing probably does not involve a trypsin-like proteinase.     

Synthesis and DNA topoisomerase-II inhibitory activity of unnatural nucleosides

The synthesis and biological activities of a number of unnatural nucleosides (23-43) is described. Nucleosides have been synthesized by SnCl4-catalyzed condensation of amino sugar acetates and silylated modified pyrimidines. Few of the 2'-O-acetyl derivatives of the nucleosides were hydrolyzed to the respective hydroxy derivatives by treatment with methanol saturated with ammonia. The compounds were screened against Filarial DNA-topoisomerase-II but only one of the compounds (29) inhibited this enzyme at 40 microg/mL of reaction mixture.     

Antiinflammatory and antioxidant evaluation of novel coumarin derivatives

Several coumarin derivatives have been reported to present multiple biological activities and especially anti-inflammatory/antioxidant activities. Recently the synthesis and in vivo/in vitro anti-inflammatory /antioxidant activities of several new coumarin derivatives with a 7-azomethine linkage have been reported. In the present study these derivatives were further tested for their antioxidant ability. Some of them were found in vitro to inhibit lipid peroxidation and to strongly scavenge superoxide radicals. Compound 3 was found to potently inhibit cyclooxygenase-1 (COX-1) and the yeast-induced rat paw oedema. The most active compounds within the set were tested against adjuvant-induced arthritis. Compound 3 was found to significantly protect the rats from adjuvant-induced arthritis (when it is administered from the first day or when it is administered the fourteenth day, with the first symptoms of the disease). An attempt was made to delineate the possible mechanism of action of the studied compounds.     

Preparation and biological activity of molecular probes to identify and analyze jasmonic acid-binding proteins

Several types of jasomonic acid (JA) derivatives, including JA--amino acid conjugates, a JA--biotin conjugate, a JA--dexamethasone heterodimer, and a JA-fluoresceine conjugate, were prepared as candidates for molecular probes to identify JA--binding proteins. These JA derivatives, excepting the JA--fluoresceine conjugate, exhibited significant biological activities in a rice seedling assay, a rice phytoalexin-inducing assay, and/or a soybean phenylalanine ammonia-lyase-inducing assay. These JA derivatives could therefore be useful probes for identifying JA--binding proteins. The activity spectra of the prepared compounds were different from each other, suggesting that different types of JA receptors were involved in the perception of JA derivatives in the respective bioassays.