Triterpenes from Euonymus revolutus

Fourteen pentacyclic triterpenes, which included ten D:A-friedooleananes, three lup-20(29)-enes and 2α,3α-dihydroxy-olean-12-en-28-oic acid, were isolated from the stem bark extract of Euonymus revolutus.     

Fluorinating π‐Extended Molecular Acceptors Yields Highly Connected Crystal Structures and Low Reorganization Energies for Efficient Solar Cells

The synthesis and characterization of new semiconducting materials is essential for developing high‐efficiency organic solar cells. Here, the synthesis, physiochemical properties, thin film morphology, and photovoltaic response of ITN‐F4 and ITzN‐F4, the first indacenodithienothiophene nonfullerene acceptors that combine π‐extension and fluorination, are reported. The neat acceptors and bulk‐heterojunction blend films with fluorinated donor polymer poly{[4,8‐bis[5‐(2‐ethylhexyl)‐4‐fluoro‐2‐thienyl]benzo[1,2‐b:4,5‐b′]‐dithiophene‐2,6‐diyl]‐alt‐[2,5‐thiophenediyl[5,7‐bis(2‐ethylhexyl)‐4,8‐dioxo‐4H,8H‐benzo[1,2‐c:4,5‐c′]dithiophene‐1,3‐diyl]]} (PBDB‐TF, also known as PM6) are investigated using a battery of techniques, including single crystal X‐ray diffraction, fs transient absorption spectroscopy (fsTA), photovoltaic response, space‐charge‐limited current transport, impedance spectroscopy, grazing incidence wide angle X‐ray scattering, and density functional theory level computation. ITN‐F4 and ITzN‐F4 are found to provide power conversion efficiencies greater and internal reorganization energies less than their non‐π‐extended and nonfluorinated counterparts when paired with PBDB‐TF. Additionally, ITN‐F4 and ITzN‐F4 exhibit favorable bulk‐heterojunction relevant single crystal packing architectures. fsTA reveals that both ITN‐F4 and ITzN‐F4 undergo ultrafast hole transfer (<300 fs) in films with PBDB‐TF, despite excimer state formation in both the neat and blend films. Taken together and in comparison to related structures, these results demonstrate that combined fluorination and π‐extension synergistically promote crystallographic π‐face‐to‐face packing, increase crystallinity, reduce internal reorganization energies, increase interplanar π–π electronic coupling, and increase power conversion efficiency.     

T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy

HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations.     

Bombesin analogs containing alpha-amino-isobutyric acid with potent anticancer activity.

Six octapeptide bombesin (BN) analogs were synthesized by substituting alpha-aminoisobutyric acid (Aib), in place of Ala9 or Gly11, or both, in the [D-Phe6, desMet14]-BN (6-14) sequence: D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-NH2 (P0). Additionally, Leu13 was replaced with isoleucine in two analogs and one of the analogs was butanoylated at the N-terminus. The antiproliferative activity of the analogs was tested in vitro on human pancreatic (MiaPaCa-2) and colon cancer (SW620, HT29 and PTC) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The analogs demonstrated anticancer activity in the above cell lines at concentrations ranging from 0.01 nM to 1 microM. One of the analogs, P6, was evaluated for in vivo tumor regression in a xenograft model of human primary colon cancer in athymic nude mice and was found to cause significant reduction in tumor volume. NMR and molecular dynamics (MD) simulation studies for this analog revealed the presence of a mixed 3(10)/alpha-helical structure. This study demonstrates that the designed BN analogs retain their anticancer activity after the incorporation of the constrained amino acid, Aib, and are potential molecules for future use in cancer therapy and drug targeting.     

Differentiation in callus cultures of a tobacco (Nicotiana tabacum cv. White Burley) variant: some biochemical aspects

A slow-growing variant plant with distinct foliar and floral morphology was obtained in tissue cultures ofNicotiana tabacum cv. White Burley. The root and shoot differentiation in the callus derived from normal plants occurred on the 8th and 12th day, respectively, but took 10 and 14 days, respectively, in the variant callus. Amylase and acid phosphatase activities, starch and soluble carbohydrate contents were studied in non-differentiating callus (NDC), root differentiating callus (RDC) and shoot differentiating callus (SDC). The activities of amylase and acid phosphatase were low in the variant as compared to normal. Maximum amylase and acid phosphatase activities coincided with the appearance of roots or shoots. There was more starch accumulation in normal callus on differentiating media, but the variant showed a less pronounced change. The normal callus under differentiating conditions also showed more increase in soluble carbohydrates as compared to the variant. The increase in soluble carbohydrate was maintained till roots and shoot appeared. The increase the variant in differentiating was reflected in slow development of enzyme activities and low starch and sugar concentrations.     

Treatment of deep mycoses with itraconazole

Four patients with deep mycoses were treated with itraconazole. Two patients had chromoblastomycosis, one patient each had aspergillosis and Rhinofacial zygomycosis. These patients were either resistant to or showed poor response to Amphotericin B and/or ketoconazole. After the initial clinical and mycological evaluation, itraconazole was given in a daily dose of 200 mg orally. All patients responded to the drug very well. No adverse effects attributable to itraconazole were detected.     

Nitrogenase. III. Nitrogenaseless mutants of Azotobacter vinelandii: Activities,cross-reactions and epr spectra

Mutant strains of Azotobacter vinelandii that are unable to fix nitrogen were analyzed for their ability to reduce acetylene and oxidize dithionite. The activities of Components I (Fe-Mo-protein) and II (Fe-protein), the presence of antibody cross-reacting material to each of the components and the electron paramagnetic resonance (EPR) intensities at g = 3.65 also were examined in these strains. All mutant strains so far studied that are unable to reduce nitrogen, are also incapable of reducing acetylene or oxidizing dithionite. Representatives of various nitrogenaseless mutants have been characterized. Based on activity measurements they fall into three classes: those lacking both components (I^?II^?), those lacking Component I (I^?II⁺) and those lacking Component II (I⁺II^?). Many strains have extremely low levels of activity for either component, but in some of these strains, cross-reacting material is made for one or both of the components. The EPR at g = 3.65 correlates well with the activity for Component I in several of these mutant strains, but in four of the mutants there appears to be 10-20-fold higher amounts of paramagnetic center than the nitrogen-fixing activity in in vitro tests would indicate.     

SYNTHESIS OF CHLOROPLAST DNA IN ISOLATED CHLOROPLASTS

Chloroplasts isolated from Euglena gracilis incorporated both tritiated thymidine 5'-triphosphate and tritiated deoxyadenosine 5'-triphosphate into an acid-stable fraction. The incorporation was dependent on the presence of all four deoxynucleoside triphosphates and was sensitive to treatment with deoxyribonuclease and actinomycin D. It was demonstrated that bacterial contamination could not account for the incorporation of label. Extraction of DNA from the chloroplasts and subsequent density gradient centrifugation of the DNA in CsCl₂ showed that the incorporation was into chloroplast DNA (ρ = 1.686) of high molecular weight.     

Lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesteryl ester metabolism in the adrenal gland of the rat.

In the adrenal gland of the rat, the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme of cholesterol synthesis, is shown to be regulated by cholesteerol carried in plasma lipoproteins. When plasma cholesterol levels were lowered 90% by administration of the drug 4-aminopyrazolopyrimidine, the cholesteryl ester content of the adrenal gland declined by more than 90% and this was associated with a 150- to 200-fold increase in the activity of adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase and a 30-fold increase in cholesterol synthesis from [14C]acetate. The subsequent intravenous infusion of cholesterol contained in either rat or human high density or low density lipoproteins restored the adrenal content of cholesteryl esters and reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase to basal levels. The depletion of adrenal cholesteryl esters and the enhancement in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that occurred in the 4-aminopyrazolopyrimidine-treated rat required the action of adrenocorticotropic hormone (ACTH) since neither was observed when ACTH secretion was blocked by administration of dexamethasone. The current data indicate that the low rate of cholesterol synthesis normally observed in the rat adrenal gland is due to a suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that is mediated by plasma lipoproteins.