Studies on new antibiotics SF2415. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities

A new species of Streptomyces is described for which the name Streptomyces aculeolatus is proposed. The organism produces new antibiotics SF2415A1, A2, A3, B1, B2 and B3 active against Gram-positive bacteria. Empirical molecular formulae of the antibiotics SF2415A1, A2, A3, B1, B2 and B3 were determined to be C26H31N2O5Cl, C26H30N2O5, C26H30N2O5Cl2, C26H33O5Cl, C26H32O5 and C26H32O5Cl2, respectively.     

Tallysomycin, a new antitumor antibiotic complex related to bleomycin. I. Production, isolation and properties

The unusual actinomycetes strain No. E465-94 produced a complex of new glycopeptide antibiotics tallysomycin, which was separated by CM-Sephadex chromatography into two major components, A (C68H107N21O27S2) and B (C62H95N19O26S2). They were isolated first in a copper-chelated form and showed physico-chemical properties similar to those of the bleomycin-group of antibiotics. Tallysomycin exhibited broad antibacterial and antifungal activity, and was highly active in vivo against bacterial infections in mice. Tallysomycins A and B demonstrated potent activity in the prophage induction of lysogenic bacteria.     

Novel thiocyanato complexes with potent cytotoxic and antimicrobial properties

The aim of the present study was to assess the cytotoxic and antimicrobial properties of seven new thiocyanato complexes: Ni(C(9)H(11)N(2)O)(SCN), Cu(C(9)H(11)N(2)O)(SCN), Pd(C(9)H(11)N(2)O)(SCN), Pt(C(9)H(11)N(2) O) (SCN), K[Ti(C(9)H(11)N(2)O)(SCN)(3)], Au(C(9)H(11)N(2)O)(SCN), and K[V(O)(C(9)H(11)N(2)O)(SCN)] (T(1)-T(7), respectively). All the complexes showed toxicity against brine shrimp nauplii (Artemia salina L.). The titanium-based complex, T(5), exhibited potent toxicity, with a lethal concentration 50% (the concentration of test compound that kills 50% of A. salina) value of 1.59 microg mL(-1). These new complexes also exhibited promising antibacterial and antifungal properties. A macrodilution technique was used to estimate the minimum inhibitory concentrations of the seven bioactive complexes. Minimum inhibitory concentrations were found to be 8-64 microg mL(-1) against the tested bacterial species.     

A54145, a new lipopeptide antibiotic complex: isolation and characterization

A54145 is a complex of acidic lipopeptide antibiotics which are produced by Streptomyces fradiae and are active against Gram-positive bacteria. The A54145 complex was isolated by adsorption on Diaion HP-20 nonfunctionalized macroreticular resin and/or ion exchange on Amberlite IRA-68 anion exchange resin. Antibacterial factors A, A1, B, B1, C, D, E, and F were obtained in purified form by repeated preparative reverse phase HPLC on C8 and/or C18 bonded-phase supports. The molecular formulae of the factors are C72H109N17O27 (factors A and A1), C73H111N17O27 (factors B, B1, C, and D), C74H113N17O27 (factor E), and C71H107N17O27 (factor F). The identities of the acyl side chains were established as 8-methylnonanoyl (factors F, A, and B1), n-decanoyl (factors A1 and B), and 8-methyldecanoyl (factors C, D, and E).     

Studies on antibiotics BN-227 and BN-227-F, new antibiotics. I. Taxonomy, isolation and characterization

The two new antibiotics, BN-227 and BN-227-F, were isolated from the fermentation broth of Pseudomonas sp. BN-227. BN-227 has a molecular formula C7H9NO3, and melts at 115 degrees C. BN-227-F has a molecular formula C21H24N3O9Fe, and melts at 156 degrees C. BN-227-F is a chelate compound consisting of three similar ligands (antibiotic BN-227) and ferric ion. The two antibiotics have antimicrobial activity against Gram-positive and Gram-negative bacteria.     

Isolation of cepafungins I, II and III from Pseudomonas species

New acylpeptide antibiotics named cepafungins I, II and III were isolated from the culture broth of a strain identified as Pseudomonas sp. These antibiotics are neutral substances, soluble in aqueous alcohols and dimethyl sulfoxide, and show UV maxima at 260.5 nm. The IR spectra indicated these to be peptides. Molecular formulas C28H46N4O6, C27H44N4O6 and C26H42N4O6 for cepafungins I, II and III were indicated by elemental analysis and SI-MS. Cepafungins exhibited inhibitory activity against yeast and fungi, and antitumor activity against P388 leukemia in mice.     

Identification of unknown impurities in simvastatin substance and tablets by liquid chromatography/tandem mass spectrometry

Unknown impurities were detected in simvastatin substance and tablets at a 0.2% level using the liquid chromatography technique with UV (DAD) detection. The impurity structures were elucidated by a direct hyphenation of liquid chromatograph to high-resolution mass spectrometer with electrospray ionisation interface using solutions of formic acid in water and in acetonitrile as the mobile phase. Peak tracking was performed using the column-switching technique. Accurate mass measurements by quadrupole time-of-flight mass spectrometer equipped with lock-spray provided information about elemental composition of intact molecules and fragments of impurities. Measurement accuracy for precursor ions was around 3 ppm and for fragment ions between 4 and 13 ppm. Mass resolving power was around 6500. Deduced molecular formulae for A1, A2 and A3 impurities were C(27)H(44)O(6), C(26)H(43)O(6) and C(26)H(41)O(5), respectively. The structures proposed for all three impurities revealed modifications of simvastatin molecule on the lactone ring. Impurity A1, detected in simvastatin tablets, was identified as ethyl ester, while the impurities A2 and A3, detected in simvastatin substance, were identified as methyl ester and methyl ether of simvastatin. The impurity from tablets was synthesized and its structure confirmed by LC-UV, LC-MS/MS, and NMR techniques.     

Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. I. Taxonomy, fermentation, isolation and physico-chemical properties

A strain of actinomycetes identified as Streptomyces flavidovirens produced new antibiotics, mureidomycins (MRD's) A approximately D, specifically active against Pseudomonas aeruginosa. They were isolated from the culture filtrate by successive column chromatographies such as Amberlite XAD-2 and CG-50, Whatman DE-52 and Toyopearl HW-40. They were amphoteric white powders and soluble in methanol and water. Their molecular weights and molecular formulae in parentheses were 840 (C38H48N8O12S), 842 (C38H50N12S), 897 (C40H51N9O13S) and 899 (C40H53N9O13S), respectively. m-Tyrosine and two unknown substances were detected by amino acid analyses as their common constituents. MRD's A and C contained uracil but MRD's B and D dihydrouracil instead of uracil.     

Metabolism of 2 alpha-propoxy-1 alpha,25-dihydroxyvitamin D3 and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1.

Recently, we demonstrated that some A-ring-modified vitamin D3 analogs had unique biological activity. Of these analogs, 2alpha-propoxy-1alpha,25(OH)2D3 (C3O1) and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)2D3 (O2C3) were examined for metabolism by CYP27A1 and CYP24A1. Surprisingly, CYP27A1 catalyzed the conversion from C3O1 to O2C3, which has 3 times more affinity for vitamin D receptor than C3O1. Thus, the conversion from C3O1 to O2C3 by CYP27A1 is considered to be a metabolic activation process. Five metabolites were detected in the metabolism of C3O1 and O2C3 by human CYP24A1 including both C-23 and C-24 oxidation pathways. On the other hand, three metabolites of the C-24 oxidation pathway were detected in their metabolism by rat CYP24A1, indicating a species-based difference in the CYP24A1-dependent metabolism of C3O1 and O2C3 between humans and rats. Kinetic analysis revealed that the Km and kcat values of human CYP24A1 for O2C3 are, respectively, approximately 16 times more and 3 times less than those for 1alpha,25(OH)2D3. Thus, the catalytic efficiency, kcat/Km, of human CYP24A1 for O2C3 is only 2% of 1alpha,25(OH)2D3. These results and a high calcium effect of C3O1 and O2C3 in animal experiments using rats suggest that C3O1 and O2C3 are promising for clinical treatment of osteoporosis.     

Characterization of flavonoids in the extract of Sophora flavescens Ait. by high-performance liquid chromatography coupled with diode-array detector and electrospray ionization mass spectrometry

A method coupling high-performance liquid chromatography (HPLC) with diode-array detector (DAD) and electrospray ionization mass spectrometry (ESI) was established for the separation and characterization of flavonoids in Sophora flavescens Ait. Based on the chromatographic separation of most flavonoids present in S. flavescens Ait., a total of 24 flavonoids were identified. Fourteen compounds were unambiguously identified comparing experimental data for retention time (t(R)), UV and MS spectra with those of the authentic compounds: 3',7-dihydroxy-4'-methoxy-isoflavone (13), trifolirhizin (14), kurarinol (18), formononetin (19), 7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (22), maackiain (21), isoxanthohumol (23), kuraridine (26), kuraridinol (27), sophoraflavanone G (30), xanthohumol (31), isokurarinone (33), kurarinone (35) and kushenol D (38), and additional 10 compounds were tentatively identified as kushenol O (10), trifolirhizin-6'-malonate (15), sophoraisoflavanone A (20), norkurarinol/kosamol Q (24), kushenol I/N (25), kushenol C (28), 2'-methoxykurarinone (29), kosamol R (32), kushecarpin A (34) and kushenol A (37) by comparing experimental data for UV and MS spectra with those of literature. Furthermore, fragmentation pathways in positive ions mode of 24 flavonoid compounds of types of flavanone, flavanonol, flavonol, chalcone, isoflavone, isoflavanone and ptercocarpane were summarized. Some common features, such as CH(3)., H(2)O, CO, CO(2), C(3)O(2) and C(2)H(2)O losses, together with Retro-Diels-Alder fragmentations were observed in the prenylated flavonoids in S. flavescens Ait. The loss of the lanandulyl chain was their characteristic fragmentation, which might help deducing the structure of unknown flavonoid compounds. The present study provided an approach to rapidly characterize bioactive constituents in S. flavescens Ait.     

Alkaloids from roots of Aconitum crassicaule

From the roots of ACONITUM CRASSICAULE, four diterpenoid alkaloids were isolated. Two of these were identified as chasmanine (5) and yunaconitine (4). The other two, Crassicauline A and Crassicauline B, are new alkaloids. The structure of crassicauline A, C (35)H (49)O (10)N, has been elucidated as structure (1) on the basis of chemical and spectral data, while the structure of crassicauline B, C (27)H (31)O (4)N, is still to be determined.     

Enhancement effect of polyoxometalates on NGF-induced neurite-outgrowth of PC12 cells

Nerve growth factor (NGF)-induced neurite-outgrowth of PC12 cells was enhanced by polyoxometalates such as Na9[SbW(9)O(33)].19.5H(2)O (SbW(9)) and (NH(3)Pr(i))6[Mo(7)O(24)].3H(2)O (Mo(7)). Western blotting analysis of polyoxometalate/NGF-treated PC12 cells showed a strong expression of growth-associated protein 43 (GAP-43), which is associated with the neurite outgrowth. Similar effects were observed for other polyoxometalates, K(11)H[(VO)3(SbW(9)O(33))2].27H(2)O ((VO)3(SbW(9))2), K6[P(2)W(18)O(62)].14H(2)O (P(2)W(18)), and K7[PTi(2)W(10)O(40)].6H2O (PTi(2)W(10)), in contrast with little effect for monomeric tungstate and molybdate. Of the polyoxometalates tested in this study, SbW(9) and Mo(7) were the most potent.     

黄褐毛忍冬化学成分的研究

从我省商品药材金银花的主要品种之一,黄褐毛忍冬(Lonicera fulvotomentosa Hsu et S.C.Cheng)的花蕾中分离到五种以常春藤皂甙元构成甙元的皂甙(Ⅰ～Ⅴ),本文报道化合物Ⅰ,Ⅱ和Ⅴ的结构测定。Ⅴ为新的三萜酸双糖链甙,命名为黄褐毛忍冬皂甙甲(fulvotomentoside A),Ⅰ和Ⅱ为已知化合物,分别被鉴定为α-常春藤皂甙(α-hederin)和无患子皂甙B(sapindoside B)。     

Studies on a new antibiotic FR-900109. 1. Taxonomy, isolation and characterization

FR-900109 is a new antibiotic obtained from fermentation broth of a streptomyces which was identified as Streptomyces prunicolor. Its elementary analysis and mass spectroscopic measurement suggest that the molecular formula is C27H32O9. It has an ultraviolet absorption maximum at 254 nm. The antibiotic is active against Gram-positive bacteria. Acute toxicity in mice is very low.     

Physico-chemical analysis of systems with a main component acetylsalicylic acid in ethanol-water mixtures. Part 3: Systems containing calcium acetylsalicylate.

The systems C9H8O4-(C9H7O4)2Ca-25% ethanol-water mixture (I), C9H8O4-(C9H7O4)2Ca-50% ethanol-water mixture (II), C9H8O4-(C9H7O4)2Ca-95% ethanol-water mixture (III) have been investigated at 15 degrees C by physico-chemical analytical methods. It was established that under the conditions of the no experiments no double or triple compounds of acetylsalicylic acid and calcium acetylsalicylate have been formed. The fields of the crystallization of the pure components are outlined. In systems I and II there exist crystallization fields of (C9H7O4)2Ca - 2H2O and in system III field of (C9H7O4)2Ca. The anhydrous salt and the crystalline hydrate were isolated and were investigated by chemical analysis and X-ray diffraction analysis.     

Design and synthesis of some novel hydrazide, 1,2-dihydropyridine, chromene derivatives carrying biologically active sulfone moieties with potential anticancer activity

This paper describes the synthesis of some novel sulfones having biologically active hydrazides (4-9, 22, 23, 26 and 27), hydrazonoyl cyanide (24), 1,2-dihydropyridines (16-21), chromene (28) and benzochromene (29) moieties starting with 1-[4-(piperidin-1-ylsulfonyl)phenyl]-ethanone 1. The structures of the the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR and 13C NMR. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (MCF7).     

Isolation and characterization of agglomerins A, B, C and D

New antibiotics, agglomerins A, B, C and D, were isolated from the culture broth of a bacterial strain identified as Enterobacter agglomerans. These antibiotics are acidic in nature and their sodium salts are obtained as colorless crystalline powders, soluble in lower alcohols. All the antibiotics shows characteristic UV maxima at 248 and 298 nm. Molecular formulas: A, C15H21O4Na; B, C17H23O4Na; C, C17H25O4Na and D, C19H27O4Na; were indicated by elemental analysis and MS. These antibiotics are active against a wide variety of anaerobic bacteria and weakly against aerobic Gram-positive bacteria in vitro.     

BMAL1对H2O2诱导的H9C2心肌细胞损伤的影响及机制探讨

目的 探讨节律基因BMAL1对过氧化氢（H2O2）诱导的H9C2心肌细胞损伤的影响及机制。方法 构建 BMAL1稳定过表达的H9C2细胞系后,实验分为2个部分。（1）实验1。对照组、H2O2组（0.2 mmol/L的H2O2处理24 h）、 BMAL1 过表达（BMAL1-OE）组（BMAL1 稳定过表达 H9C2 细胞）、BMAL1 过表达+H2O2（BMAL1-OE+H2O2）组 （0.2 mmol/L的H2O2处理BMAL1稳定过表达H9C2细胞24 h）。（2）实验2。H2O2组、BMAL1-OE+H2O2组、BMAL1过表 达+抑制 NRF2+H2O2（BMAL1-OE+ML385+H2O2）组（NRF2 抑制剂 2 μmol/L 的 ML385 预处理 BMAL1 稳定过表达 H9C2 细胞 24 h,再用 0.2 mmol/L 的 H2O2处理 24 h）、BMAL1 过表达+抑制 HO-1+H2O2（BMAL1-OE+Znpp+H2O2）组 （HO-1抑制剂5 μmol/L的Znpp预处理BMAL1稳定过表达H9C2细胞24 h,再用0.2 mmol/L的H2O2处理24 h）。CCK-8 法检测细胞活力,羟胺法检测超氧化物歧化酶（SOD）活性、TBA 法检测丙二醛（MDA）含量,Western blot 法检测 BMAL1、核因子 E2 相关因子 2（NRF2）和血红素加氧酶-1（HO-1）蛋白表达水平。结果 （1）与 Control 组相比, BMAL1-OE组BMAL1 mRNA表达水平升高,H2O2组细胞活力和细胞上清液SOD活性下降、MDA含量增加,BMAL1、 NRF2和HO-1蛋白相对表达水平降低（P＜0.05）;与H2O2组相比,BMAL1-OE+H2O2组细胞活力和细胞上清液SOD活 性增加,MDA 含量减少,而 BMAL1、NRF2 和 HO-1 蛋白相对表达水平升高（P＜0.05）;（2）与 BMAL1-OE+H2O2组相 比,BMAL1-OE+ML385+H2O2组和BMAL1-OE+Znpp+H2O2组细胞活力和细胞上清液SOD活性降低,MDA含量增加 （P＜0.05）。结论 BMAL1可能通过上调NRF2/HO-1信号轴,减轻H2O2诱导的大鼠心肌细胞氧化应激损伤。     

OF4949, new inhibitors of aminopeptidase B. I. Taxonomy, fermentation, isolation and characterization

New aminopeptidase B inhibitors that we named OF4949-I, II, III and IV were isolated from the culture broth of a fungus, Penicillium rugulosum OF4949. The molecular formula of I was C23H26N4O8 and that of II, C22H24O8, judging from elemental analysis and secondary ion mass spectrometry. The concentrations of I, II, III and IV required for 50% inhibition of aminopeptidase, using Ehrlich ascites carcinoma cells as the source of the enzyme, were 0.0054, 0.0048, 3.4 and 1.7 micrograms/ml, respectively. Components I and II augmented delayed-type hypersensitivity in mice to sheep red blood cells.     

Structures of Crassicaulisine and Crassicaulidine, two New Diterpenoid Alkaloids

From the roots of ACONITUM CRASSICAULE, two new diterpenoid alkaloids, crassicaulisine and crassicaulidine, were isolated. The structure of crassicaulisine, C (24)H (39)O (7)N, has been elucidated as 3 on the basis of chemical and spectral data, while the structure of crassicaulidine, C (24)H (39)O (8)N, has been shown as 4 on the basis of chemical data and spectral comparison with crassicaulisine.