Asitrocin, (2,4)-cis- and trans-asitrocinones: novel bioactive mono-tetrahydrofuran acetogenins from Asimina triloba seeds.

Asitrocin (1) and the mixture of (2,4)-cis- and trans-asitrocinones (2 and 3), new bioactive Annonaceous acetogenins, were isolated from the seeds of Asimina triloba by activity-directed fractionation using the brine shrimp lethality test. Asitrocin and the mixture of (2,4)-cis- and trans-asitrocinones have a configuration of erythro/trans/threo from C-15 to C-20, the mono-THF moiety with two flanking hydroxyl groups. The structures were determined by spectroscopic methods. These acetogenins showed potent bioactivities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the prostate (PC-3) and the pancreatic (MIA PaCa-2) cell lines at 10-100 times the potency of adriamycin.

cis-Annonacin and (2,4)-cis-and trans-isoannonacins: cytotoxic monotetrahydrofuran annonaceous acetogenins from the seeds of Annona cherimolia.

cis-Annonacin (1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 and 3), three known mono-tetrahydrofuran annonaceous acetogenins, have been isolated from the seeds of Annona cherimolia by the use of the brine shrimp lethality test (BST) for bioactivity directed fractionation. Their structures were elucidated based on spectroscopic and chemical methods. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1,000 times the potency of adriamycin. The mixture of 2 and 3 is over 10,000 times cytotoxic as adriamycin in the pancreatic cell line (PaCa-2). All of the compounds are about 10 to 100 times as cytotoxic as adriamycin in the prostate cell line (PC-3).

Annocherin and (2,4)-cis- and trans-annocherinones, monotetrahydrofuran Annonaceous acetogenins with a C-7 carbonyl group from Annona cherimolia seeds.

The new cytotoxic monotetrahydrofuran Annonaceous acetogenins, annocherin (1) and a mixture of (2,4)-cis- and trans-annocherinones (2 and 3), were isolated from the bioactive methanolic extract of Annonacherimolia seeds. Compounds 1-3 each possess an unusual 7-carbonyl group. Their structures were established on the basis of chemical and spectral evidence. Compounds 1-3 showed significant toxicity in the brine shrimp lethality test and cytotoxicity for six human solid tumor cell lines, with selectivity for the renal cell line (A-498) at potencies equivalent to Adriamycin.

Antinociceptive effect of smilaxin B administered intracerebroventricularly in the mouse.

We examined the antinociceptive effect of smilaxin B administered intracerebroventricularly (i.c.v.) in ICR mice. The tail-flick test was used as an analgesic assay. Smilaxin B showed a strong antinociceptive effect in a dose-dependent manner. Sulfated cholecystokinin (CCK-8s, 0.5 ng), muscimol (50ng), or MK-801 [(+/-)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]cyclohepten-5, 10-imine maleate, 1 microgram] injected i.c.v. significantly reduced inhibition of the tail-flick response induced by smilaxin B administered i.c.v. However, naloxone (2 microgram), baclofen (10 ng), or CNQX (6-cyano-7- nitroquinoxaline-2,3-dione, 0.5 microgram) injected i.c.v. did not affect inhibition of the tail-flick response induced by similaxin B administered i.c.v. The intrathecal (i.t.) injection of yohimbine (20 micrograms), but not methysergide (20 micrograms) and naloxone (2 microgram), significantly attenuated inhibition of the tail-flick response. induced by smilaxin B administered i.c.v. Our results suggest that GABAA or NMDA receptors but not opioid, GABAB, and non-NMDA receptors located at the supraspinal level may play important roles in the production of antinociception induced by smilaxin B administered supraspinally. Furthermore, smilaxin B administered supraspinally. may produce its antinociception by activating descending noradrenergic- but not opioidergic- and serotonergic-neurons.

Longicin and goniothalamicinone: novel bioactive monotetrahydrofuran acetogenins from Asimina longifolia.

Longicin [1] and (2,4-cis and trans)-goniothalamicinone [2], two new monotetrahydrofuran Annonaceous acetogenins, have been isolated from the leaves and twigs of Asimina longifolia (the long leaf paw paw) by the use of the brine shrimp lethality test for bioactivity-directed fractionation. The structures were elucidated based on spectroscopic and chemical methods. Compound 1 was converted to its ketolactone isomer, (2,4-cis and trans)-longicinone [3], to aid the stereochemical elucidation of 1. Compounds 1-3 showed selective and potent cytotoxicities to certain human tumor cell lines, with the potency of 1 against pancreatic carcinoma (PaCa-2) over one million times that of adriamycin. Nine known cytotoxic acetogenins, annonacin, xylomaticin, isoannonacin, gigantetrocins A and B, muricatetrocins A and B, gigantetrocin-A-one and goniothalamicin, were also isolated for the first time from this species.

[The effect of various cleansing methods for total fiber optic colonoscopy].

It is a fact that there are recent increasing trends of incidence of the colorectal carcinoma among other colorectal diseases. In such trend, the early detection remain to be most important by the air contrast barium enema and total fiber optic colonoscopy There are several ways to prepare the colon for barium enema and fiber optic colonoscopy which include several agents. The mechanical cleansing have been used most frequently since Brown's method was adapted to be most perfect for colon cleansing. The ideal laxatives and enema solutions were limited to adequate dose, it's effectiveness, patient's diet and bowel habit, minimal side effect, low cost and simple to perform. In order to compare the effectiveness of various cleansing solutions, six experimental methods were formed as shown; 1. normal saline enema, 2. castor oil with normal saline enema, 3. castor oil with soapsuds enema, 4. magnesium citrate with normal saline, 5. magnesium citrate with soapsuds enema and 6. ingestion of Golyetly solution. The authors have compared and determined the degree of cleanliness by an experienced endoscopist The total number of patients was 247, age distribution was 43 +/- 15 years old, and sex distribution was 133 males and 114 females. The grade I and II represented no difficulties at performing the fiber optic colonoscopy+, but grade III and IV had some difficulties, even unable to perform the fiber optic colonoscopy. The effectiveness the cleansing agents, represented with grade I and II was 95.9% (47/49) in method 6, 93.2% (54/58) in method 2, 83.3% (30/33) in method 3, 70.0% (28/40) in method 5, 66.7% (16/24) in method 1, and 45.7% (18/40) in method 4. Method 2 and 6 were the most effective in normal bowel habit patients. In constipated patients, method 6 was the most effective and all method except method 4 were effective in diarrhea patients. The degrees of less mucosal irritation by various bowel cleansing method were in the order of method 6(100%), 1(100%), 5(74%), 2(69%). In subjective symptoms and cleansing groups, abdominal distension, pain, nausea and vomiting were complained, and that's subject symptoms were in the order of method 3(88.9%), 6(79.6%), 1(75%), 5(72.5%), 2(72.4%), 4(67.5%). In conclusion, we believe that the Golytely of the mechanical cleansing solution for fiber optic colonoscopy was the most effective, but others depended on the patient's condition and bowel habit.