Acyl-CoA:Cholesterol Acyltransferase Inhibitory Activity of Lignans Isolated from Schizandra, Machilus and Magnolia Species

Fifteen lignans were isolated from the fruits of SCHIZANDRA CHINENSIS, the leaves of MACHILUS THUNBERGII, and the flower buds of MAGNOLIA DENUDATA. They were identified as gomisins, schizandrin, wuweizisu, schizantherin, licarins, and machilin, which inhibited rat liver ACAT with IC (50) values of 25-200 microM. Comisin N is the most potent inhibitor with IC (50) value of 25 microM in these lignans.     

Bioisosterism: Interchange of 4-OH to 4-NH2 in vanillin or homovanillin ring of capsaicinoids

A series of 4-amino Capsaicin analogs 15, 17 and 19 were prepared to investigate the bioisosteric effect of 4-amino group, and all these compounds exhibited moderate or weak potency from their analgesic test. From our previous results and others, 4-hydroxyl group as well as 3-methoxy substituent could be crucial for high analgesic activity. This biological result also shows that the activity is sensitive to alkyl chain length in hydrophobic region and the phenylacetic amides 19 are more active than the corresponding urea derivatives 17.     

Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillin-resistantStaphylococcus aureus and the DNA gyrase-inhibitory activity

Psammaplin A, a natural bromotyrosine derivative from an associated form of two sponges (Poecillastra sp. and Jaspis sp.) was found to possess the antimicrobial effect on the Gram-positive bacteria, especially on methicillin-resistant Staphylococcus aureus (MRSA). The minimal inhibitory concentration of psammaplin A against twenty one MRSAs ranged from 0.781 to 6.25 microg/ml, while that of ciprofloxacin was 0.391-3.125 microg/ml. Psammaplin A could not bind to penicillin binding protein, but inhibited the DNA synthesis and the DNA gyrase activity with the respective 50% (DNA synthesis) and 100% (DNA gyrase) inhibitory concentration 2.83 and 100 microg/ml. These results indicate that psammaplin A has a considerable antibacterial activity, although restricted to a somewhat narrow range of bacteria, probably by inhibiting DNA gyrase.     

Synthesis of 4-hydroxy-1-thiocoumarin derivatives-1: An efficient synthesis of thioflocoumafen

An efficient procedure for the preparation of 4-hydroxy-3-{1,2,3,4-tetra-hydro-3-[4-(4-triflu-oromethylbenzyl oxy)phenyl]-1-naphthyl}thiocoumarin (thioflocoumafen, 1a and 1b) is described. The key step in the synthesis involves the condensation reaction of 3-(4-methoxyphenyl)-1-tetralol (2) with 4-hydroxy-1-thiocoumarin (3).     

Synthesis andin vitro antibacterial activity of C-3′ pyridinium cephalosporin derivatives

The quaternary ammonium cephalosporin derivatives were prepared with various pyridines substituted at the 3 or/and 4 position. Their in vitro antibacterial activities were determined and substituent effect on pyridine nucleus was studied. Preparation of substituted pyridines are also described.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Effect of DW2282 on the induction of methemoglobinemia, hypoglycemia or WBC count and hematological changes

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl] -4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induce methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it does produce.     

Esters of substituted benzoic acids as anti-thrombotic agents

Aliphatic esters of protocatechuic acid (PA,1), vanillic acid (VA,9) and gallic acid (GA,18) were prepared and their anti-thrombotic effects were evaluated in the mouse model of thrombosis. The aliphatic groups included methyl, ethyl,n-propyl,i-propyl,n-butyl,i-butyl,n-amyl and cyclohexyl.n-Amyl ester of PA (7), i-propyl and cyclohexyl esters of VA (13 and17 respectively) and ethyl ester of GA (20) treatment significantly lowered the death rate and increased the recovery from paralysis due to the thrombotic challenge. From the limited analogs available, it was tentatively concluded that the structural conformation, where carboxy oxygen (=O or-O^?) of the carboxyl group (COOH) at C₁ and the oxygen function at C₃ (either OH or OCH₃) are closely situated, is favorable for the esters of PA, VA and GA to be more antithrombotic.     

Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury.

A bilayer artificial skin composed of a temporary Silastic epidermis and a porous collagen-chondroitn 6-sulfate fibrillar dermis, which is not removed, has been used to physiologically close up to 60% of the body surface following prompt excision of burn wounds in ten patients whose total burn size covered 50--95% body surface area (BSA). Following grafting, the dermal portion is populated with fibroblasts and vessels from the wound bed. The anatomic structure of the artificial dermis resembles normal dermis and serves as a template for the synthesis of new connective tissue and the formation of a "neodermis," while it is slowly biodegraded. This artificial skin has physiologically closed excised burn wounds for periods of time up to 46 days before the Silastic epidermis was removed. At the time of election when donor sites are ready for reharvesting, the Silastic epidermis is removed from the vascularized artificial dermis and replaced with 0.004 autoepidermal graft in sheet or meshed form. Clinical and histologic experience in a relatively short follow-up period (2--16 months) indicates that "neodermis" retains some of the anatomic characteristics and behavior of normal dermis, thus promising improvement in the functional and cosmetic results, as well as providing physiologic function as a skin substitute. The artificial skin is easily sterilized and stored at room temperature, capable of large scale production, and immediately available for grafting, indicating its potential for easy and relatively economic use in the burn patient.     

Distortion-product and click-evoked otoacoustic emissions in healthy newborns.

Distortion-product otoacoustic emissions (DPOEs) are believed to provide frequency-specific information about cochlear function. The DPOEs have been reported in the adult population but have not been reported previously in the neonatal population. We recorded DPOEs from a group of healthy full-term newborn human subjects (35 ears) to establish the characteristics of these emissions in the newborn population. To our knowledge, this is the first study of DPOEs in newborns. The "DPOE audiograms" from the newborns tested revealed characteristics qualitatively similar to those seen in adults with normal hearing. This study demonstrates the feasibility of DPOE measurements among newborns and provides a normal baseline for this age group, thus fulfilling a necessary step toward the development of an objective, noninvasive frequency-specific test of cochlear function. Click-evoked otoacoustic emissions were also recorded from the newborn population and compared with click-evoked otoacoustic emissions from adults. The spectrum of the click-evoked emissions was variable and individualistic, similar to findings previously reported in adult subjects. The click-evoked otoacoustic emissions of the newborns had a higher overall level and contained stronger high-frequency (4.5 to 6 kHz) spectral components than those of the adults. We also found that the low-frequency components of the click stimulus spectrum were attenuated in the neonatal ears exhibiting a high-pass slope below about 2.5 kHz, whereas the stimulus spectrum was nearly flat in this frequency region in adult ears.