二氧化钛包裹竹红菌素纳米粒的制备和表征

采用溶胶-凝胶法合成二氧化钛包裹竹红菌素纳米粒,并利用透射电镜和粒度分析仪对其形貌和粒子大小进行测定,证明粒子呈球形,平均直径在100 nm左右;采用紫外和荧光光谱研究二氧化钛包裹竹红菌素纳米粒的光谱性质,并与未包裹的竹红菌素在水溶液中的光谱性质进行了比较,结果表明,竹红菌素被成功地包裹于二氧化钛纳米粒中;包裹后竹红菌素的光谱吸收峰红移,强度增加.由此,将有利于竹红菌素在光动力疗法中的应用.     

竹红菌素中试提纯工艺及抑菌活性研究

为了研究竹红菌素的中试提纯工艺及抑菌效果，在中试生产中，通过不同溶剂、提取方法提取竹红菌素，研究盐析法、降温法和超滤法对竹红菌素的纯化效果。结果表明使用气流粉碎法竹红菌素提取量可达21.4 mg/g,超滤法纯化后，竹红菌素的纯度达到90%以上。对竹红菌素的抑菌活性分析发现，其热稳定性良好，并且对大肠埃希氏菌和白色念珠菌均有抑制作用。竹红菌素具有天然抗菌和良好的热稳定性，易提取纯化，可作为一种抑菌药物应用到医药等领域。     

纳米二氧化钛负载1,4-二羟基蒽醌的机理研究

蒽醌类化合物是天然植物药中具有重要生物活性和药效功能的物质,可用作降血糖、降胆固醇、通便利尿、抗氧化、抗过氧化、促智、抗衰老等,尤其是蒽醌类化合物还是自然界中广泛存在的一类天然光敏剂,使其在光动力疗法研究领域中受到广泛的关注.已见报道具有光敏治疗肿瘤活性的蒽醌类化合物主要有金丝桃素、痂囊腔菌素和竹红菌素等,此类药物通常以DNA为作用靶点,在光照射条件下光敏损伤DNA     

竹红菌素研究的进展

竹红菌素(Hypocrellin)是在我国最早发现的一种新型光敏剂.它的光生物活性可抑制细菌生长.近几年的研究表明,细胞吸收后,它主要分布于细胞膜及胞浆中,只有少量的进入细胞核中.竹红菌素加光照后对细胞具有明显的杀伤作用,使细胞存活率显著下降.竹红菌素光敏作用靶部位是细胞膜,线粒体和微粒体是其敏感靶部位,而光敏作用引发的脂自由基等产物可能是诱导DNA等损伤,最终导致细胞死亡的重要原因.     

利用分子印迹固相萃取法进行竹红菌素精制的研究

选用沉淀聚合法合成竹红菌甲素分子印迹聚合物(molecular imprinted polymer,MIP)和竹红菌乙素MIP,研究了基于分子印迹聚合物的竹红菌素发酵液的静态吸附和解吸.利用干法填装竹红菌甲素MIP、竹红菌乙素MIP和制备型固相萃取柱,对竹红菌素提取浓缩液进行了竹红菌甲素和乙素的分离与精制.结果表明:混合吸附的最佳填充柱组合为竹红菌甲素MIP 10.5,g、竹红菌乙素MIP为4.5,g,洗脱次序为先洗脱竹红菌甲素,更换淋洗剂后,再洗脱竹红菌乙素.     

竹红菌甲素和溶菌酶之间的电子转移与荧光猝灭作用

在光动力疗法中,竹红菌甲素作为敏剂与溶菌酶发生了相互作用.本文对竹红菌甲素同溶菌酶作用的荧光猝灭机理进行了研究.结果表明,竹红菌甲素与溶菌酶结构中的酪氨酸和色氨酸之间的光诱导电子转移机制,在荧光猝灭过程中起了重要作用.     

滇西竹黄抗菌活性研究

采用索氏提取法和酸碱沉淀法提取了产自滇西竹黄中的竹红菌素,并用纸碟法对竹红菌素进行抗茵活性检测．结果表明：滇西竹黄提取物对革兰氏阳性菌抑制效果明显,对革兰氏阴性菌抑制效果不明显,对霉菌有部分抑菌效果．     

从竹红菌及竹黑菌、竹黄中提取甘露醇的方法

竹红菌(Hypocrella bambusae)及竹黑菌(H.SP)竹黄(Shiria bambusicola)系子襄菌纲肉座菌科的竹寄生真菌。其中竹红菌和竹黄是民间用于治疗胃病及风湿关节炎的中药。近几年来对上述真菌进行了深入研究,从中分离到了竹红竹甲素(简称甲素)及其同系物,使用甲素治疗外阴白色病变和疤痕疙瘩取得了明显疗效,为我国首创的光化学疗法药物。为了充分利用上述三种真菌资源我们开展了综合利用的研究。 我们从竹红菌及竹黑菌、竹黄中分别分离得到了D—甘露醇,按生药风干重计,获得率依次为4％、0.6％、0.6％。D—甘露醇用于治疗脑水肿、休克、循环虚脱、烫伤烧伤,可作为生化试剂,炸药原料,工业上用于电镀液、电溶及合成树脂等。在竹红菌素药物生产中,D—甘露作为一个付产品获得,是经济可行的。兹将竹红苗、竹黑菌及竹黄中D—甘露醇的分离、鉴定及提取流程报告如下。     

竹红菌甲素和竹红菌乙素的光电转换性能

通过光电转换检测系统对竹红菌甲素和竹红菌乙素的光电转换性能进行了研究，结果表明两种光敏剂均具有良好的光敏性能，其中竹红菌甲素光敏电极无论是光电流还是光电压均要大于竹红菌乙素光敏电极，说明竹红菌甲素比竹红菌乙素的光敏性能更佳．     

蛇足石杉内生真菌Shiraia sp. Slf14中III型聚酮合酶的表达、纯化及生物信息学分析

竹红菌素是我国特有的一类苝醌类光敏色素,在开发新型抗肿瘤抗病毒药物、光敏活性农药及新型光电转换材料等方面应用前景广阔.聚酮合酶（ Polyketide synthase,PKS）是合成竹红菌素的一种关键酶,通过全基因组测序及分析发现在Shiraia sp. Slf14中存在一个III型聚酮合酶基因.利用RT-PCR技术,以其总RNA为模板,扩增得到目的片段,并成功构建表达载体pET-22b（+）-PKSIII,采用Ni-NTA亲和层析法纯化目的蛋白,在大肠杆菌BL21（ DE3）中成功表达出了目的蛋白,SDS-PAGE结果显示表达重组产物分子质量约为43 kDa,与理论值一致,为III型聚酮合酶的催化活性研究提供理论依据.     

Photochemistry of hypocrellin derivatives under aerobic conditions

Hypocrellins are a novel type of photosensitizers. A series of new hypocrellin B (HB) derivatives have been synthesized to overcome their limitations, i.e. to improve their red absorption and amphiphilicity. The generation of reactive oxygen species (including Superoxide anion radical, hydroxyl radical and singlet oxygen) is investigated in the presence of oxygen. The chemical structures of HB derivatives affect not only the generation efficiencies of Superoxide and hydroxyl radicals, but also quantum yields of singlet oxygen.     

Novel phototherapeutic agents： Investigation and progress of hypocrellin derivatives

Hypocrellins, as a kind of novel phototherapeutic agents, have several advantages over the clinically used hematoporphyrin derivatives, including high-excited triplet state yield, high phototoxicity, low dark toxicity, and rapid metabolism. However, they exhibit little absorption in the photodynamic window (600--900 nm) and are not water soluble, which limits their application in photodynamic therapy. Sulfonated and metal-ioned hypocrellins have been designed and synthesized to improve their water solubility.Unfortunately, the water-soluble derivatives obtained exhibit lower photodynamic activity than the parent hypocrellins.Thiolated and aminated hypocrellins have also been designed and synthesized to enlarge their photoresponse. Among them,the aminated hypocrellins possess the highest photodynamic activity. We recently have further designed and synthesized some amphiphilic aminated hypocrellin derivatives. Thus,not only the photoresponse but also the water solubility is enhanced. The experiments in vitro and in vivo on the derivatives are under way at present.     

Photophysical and photosensitive properties of Elsinochrome A

1 Introduction The perylenequinone compounds found in living creatures possess photodynamic activity to tumors and viruses and have drawn world-wide attention[1―4]However, their clinical application may be restrained due to the shortage of the natural re…     

Optimization of hypocrellin B derivative amphiphilicity and biological activity

To satisfy the dual requirements of the fluent transportation in blood and the affinity to the target tissues of vascular diseases, hypocrellin derivatives with optimized amphiphilicity are expected. In this work, 3-amino-l-propanesulfonic acid and 4-amino-l-butanesulfonic acid substituted hypocrellin B, named compounds 1 and 2, were designed, synthesized in high yields and characterized. Besides greatly strengthened red absorption, the maximum solubility of compound 2 in phosphate buffered saline （PBS） is 4.2 mg/mL which is just enough to prepare an aqueous solution for intravenous injection in clinically acceptable concentration, while the partition coefficient between n-octanol and PBS, 5.6, benefits the cell-uptake and biological activity as well. Furthermore, EPR measurements reveal that the photosensitization activities of the two compounds to generate semiquinone anion radicals, superoxide anion radicals and singlet oxygen are a little bit higher than those of taurine substituted hypocrellin B （THB）, but the photodynamic activities to human lung cancer A549 cells are several times that of THB, mainly due to increases in lipophilicity and cell-uptake.     

产生苝醌类化合物真菌的化学成分及光敏活性研究

 研究菌寄生菌属真菌(Ascomycetes Hypocreaceae Hypomyces(Fr.)Tul.sp.)菌丝体的化学成分.用丙酮回流提取,用二氯甲烷和甲醇洗脱,硅胶H柱层析分离,化学与波谱学进行结构鉴定.从菌丝体中分离得4个化合物,分别鉴定为甘露醇(I),痂囊腔菌素A(II),竹红菌甲素(III)和竹红菌乙素(IV).用微生物纸片法测定了化合物II,III,IV的光敏活性.     

新型光敏剂的合成研究

在醋酸和醋酐溶剂中,用硝酸盐作硝化剂,与四苯基金属卟啉进行区域选择性硝化反应,制备了一系列新型用于光动力治疗光敏剂研究的2-硝基-四(3-甲氧基苯基)卟啉,产率达90%以上.用红外光谱、紫外-可见光谱、核磁共振谱和质谱对这些化合物进行了分析和鉴证,各项指标均符合要求.     

Photochemistry of hypocrellin derivatives under anaerobic conditions

To improve the red absorption and solubility of hypocrellin, we have synthesized a series of hypocrellin B derivatives. The photochemistry of these new compounds in anaerobic media has been investigated by using electronic paramagnetic resonance (EPR) and spectrophotometric methods. The semiquinone anion radicals can be produced by self-electron transfer on irradiation, with the formation efficiency and EPR hyperfine structures of the semiquinone anion radicals dependent on the structures of the derivatives. When an electron donor is present, the electron transfer from electron donor to hypocrellin B derivatives enhanced the production of the corresponding semiquinone anion radical; in addition, the semiquinone anion radical and hydroquinone can be detected spectrophotometrically. Structural modifications exert little effect on the absorption position of semiquinone anion radical and hydroquinone, but influence their formation efficiency significantly.     

竹红菌甲素和马心肌红蛋白相互作用的光谱研究

利用紫外可见吸收光谱和荧光光谱研究了竹红菌甲素(HA)与肌红蛋白(Mb)的相互作用．结果表明两者的相互作用主要存在于竹红菌甲素与马心肌红蛋白分子中的氨基酸残基之间．