Epivernadol diacetate

In the crystal structure of the title compound, (4aR,5R,6S,7S,8aS)-methyl 8a-ethenyloctahydro-5-acetoxy-7-{[2-(acetoxymethyl)-1-oxo-2-propenyl]oxy}-[alpha],4-bis(methylene)-3-oxo-1H-2-benzopyran-6-acetate, C24H28O10, the molecule has a cis configuration at the junction of the two six-membered rings and not a trans configuration as was assigned on the basis of NMR data in solution [Asaka et al. (1977). Phytochemistry, 16, 1838-1839]

Selective Th1 upregulation by ethyl acetate fraction of Labisia pumila

Aim of the study: Labisia pumila has rejuvenating properties that help women to regain the strength and vigour after giving birth (Burkill, 1935) leading us to speculate that Labisia pumila might also modulate the immune matrix as it is one of the important aspect of healthy state of the living body. Materials and methods: Studies were carried out for the evaluation of pro-inflammatory cytokines in murine neutrophils followed by expression of T cell-surface markers and corresponding intracellular expression of cytokines related to T helper1 (Th1) and T helper 2 (Th2) activity. Results: The ethyl acetate fraction (A001/3b) obtained from ethanolic extract of leaves of Labisia pumila at graded doses (in vitro) showed increased expression of TNF-�, IL-6 and IL-12. IL-12 is a strong inducer of Th1 response in activated CD4+ T cells and accordingly T cell studies were carried out (in vivo). These specific studies showed A001/3b to cause marked stimulation of CD4+ T helper cells and related cytokine expression like IL-2 and IFN-gamma (a potent Th1 inducer), thereby, having a predominant Th1 upregulation pathway. This was further validated by suppression of IL-4 and IL-10 expression which are the Th2 pathway cytokines. Conclusion: This study showed ethyl acetate fraction (A001/3b) of Labisia pumila to have Th1 upregulating activity and suggests its possible usefulness as a therapeutic agent in immune compromised patients

Enzymatic resolution of naproxen

Trichosporon sp. (TSL), a newly found strain isolated from a locally fermented cottage cheese has been found to be highly stereoselective in the resolution of(S)-(+)-naproxen (ee >99%, E�500) from the corresponding racemic methyl ester. The process of resolution using whole cells has been scaled up to multi-kg level. Optimization of experimental conditions including downstream processing at 80–100 g/L substrate concentration with >90% recovery has been achieved. Changes in the physical parameters such as the particle size of the substrate play an important role in the resolution kinetics. A new strain of Trichosporon sp. having high cell density in cultivation (>60 g dry cell mass L−1 in 14–16 h) is found to be sufficiently stable for two years in dry powder form at 5–8°C. The viability of the resolution process has been further improved by the development of a simple racemization process for the enriched (R)-(−)-ester

Arthrobacter sp. lipase immobilization for improvement in stability and enantioselectivity

Arthrobacter sp. lipase (ABL, MTCC no. 5125)is being recognized as an efficient enzyme for the resolution of drugs and their intermediates. The immobilization of ABL on various matrices for its enantioselectivity,stability, and reusability has been studied. Immobilization by covalent bonding on sepharose and silica afforded a maximum of 380 and 40 IU/g activity, respectively,whereas sol 13gel entrapment provided a maximum of 150 IU/g activity in dry powder. The immobilized enzyme displayed excellent stability in the pH range of 4 1310 and even at higher temperature, i.e., 50 136

Protective Effect ofLabisia pumilaon Stress-Induced Behavioral, Biochemical, and Immunological Alterations

The aim of the present study was to investigate the antistress potential of LABISIA PUMILA aqueous extract (LPPM/A003) using a battery of tests widely employed in different stressful situations. Pretreatment of experimental animals with LPPM/A003 caused an increase in the swimming endurance and hypoxia time and also showed the recovery of physical stress-induced depletion of neuromuscular coordination and scopolamine induced memory deficit. LPPM/A003 at graded doses reversed the chronic restraint stress (RST), induced depletion of CD4 and CD8 T lymphocytes, NK cell population, and corresponding cytokines expression besides downregulating the stress-induced increase in plasma corticosterone, a major stress hormone. In addition, LPPM/A003 reversed the chronic stress-induced increase in adrenal gland weight, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and hepatic lipid peroxidation (LP) levels and augmented the RST induced decrease in hepatic glutathione (GSH), thymus and spleen weight. Thus, we conclude that LPPM/A003 has the ability to reverse the alterations produced by various stressful stimuli and therefore restores homeostasis

Enantioselectivity modulation through immobilization of Arthrobacter sp. lipase: Kinetic resolution of fluoxetine intermediate

Arthrobacter sp. lipase (ABL, MTCC no. 5125) has been identified for its excellent performance in kinetic resolution of a number of drug intermediates. ABL free enzyme provided product II and V (ee < 95%) from racemic fluoxetine intermediate (I and IV) compared to its cell biomass in naturally immobilized state (ee < 98%). To overcome this problem and obtaining high enantioselectivity (R isomer ee 99%), ABL enzyme was modulated by immobilization using various methods vis-`a-vis substrate modification (Scheme 2). Immobilized enzyme obtained by hydrophobic binding provided 6710–7720 U/g, covalent binding 200 U/g, and sol–gel entrapment 65–110 U/g activity. Substantial improvement in enantioselectivity was obtained using acylates of ethyl 3-hydroxy 3-phenylpropanoate a fluoxetine drug intermediate (R isomer ee from 93 to 99% and E from 43 to 127–473) at 29–45% conversion in fixed time period of 21 h, indicating thereby some change in conformation of ABL immobilized enzyme. The ABL immobilized by covalent binding and sol–gel entrapment has demonstrated reasonable superiority over the free ABL in enantioselectivity as well as over all rate of hydrolysis. Immobilized enzymes prepared by covalent and entrapment methods have shown excellent operational stability and used for 10 cycles without loss in activity and the technique can be upscaled for process development

Trichosporon beigelli esterase (TBE): a versatile esterase for the resolution of economically important racemates

A hydrolase producing strain Trichosporon beigelli esterase (TBE) isolated from local cottage cheese in its native form has displayed versatility and high efficacy in the kinetic resolution of a wide range of economically important substrates, which include racemic secondary alcohols, such as 1-(6-methoxy-2-naphthyl)ethanol (E � 316), 1-(3,4-methylenedioxyphenyl)ethanol and pentanol(E � 180 and 156 resp.), and alkyl esters of carboxylic acids such as ibuprofen (E � 340), 2-(benzylthio)propanoic acid (E � 1000). In other substrates such as in the primary alcohol 2-(6-methoxy-2-naphthyl)propan-1-ol and carboxylic acids such as 2-(5-bromo-6-methoxy-2-naphthyl)propanoic acid, 2-(2-naphthyloxy)propanoic acid, and substituted 2-thiopropanoic acids, it displayed moderate to low selectivity. Commercial lipases such as CCL, PPL, and PSL were also used in the resolution of the substrates for comparative studies