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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules and Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
Editor in Chief :
Volume & Issues
Volume 5, Issue 4 - Dec 1997
Volume 5, Issue 3 - Sep 1997
Volume 5, Issue 2 - Jun 1997
Volume 5, Issue 1 - Mar 1997
Selecting the target year
Regeneration of Pinusolide from Its 17-Nor-8-oxo Derivative
Han, Byung-Hoon ; Song, Wan-Jin ; No, Kwnag-Hyun ;
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 107~109
For metabolic study of pinusolide, a naturally occurring platelet activating factor antagonist, a synthetic method for preparation of radiolabeled pinusolide was studied. Pinusolide was first oxidized with
to 17-nor-8-oxo compound (2), which was subsequently converted to pinusolide by treatment with the Lombardo reagent
. The Wittily reaction was unsuccessful in the latter carbonyl methylenation of 2.
Effect of G-CSF on Myelosuppression and Antitumor Effect of DA-125, a Novel Adfiamycin Derivative
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 110~116
The present study was designed to evaluate the effects of a recombinant human granulocyte-colony stimulating factor (G-CSF) on leukopenia and tumor growth in mice treated with DA-125, an adri-amycin (ADM) derivative. In normal mice, single intravenous injection of DA-125 produced transient leukopenia accompanied with weight loss and splenic atrophy in a dose-related manner. However, subcutane-ous administration of G-CSF (5
g/head) for 5 consecutive days after DA-125 resulted in a significantly elevated nadir of leukocyte counts and facilitation of recovery from the leukopenia. To investigate the effect of G-CSF on antitumor effects of DA-125, ADM (12 mg/kg) or DA-125 (40 mg/kg) was administered to Colon-26 murine adenocarcinoma-bearing Balb/c mice with G-CSF. Regardless of treatment with G-CSF, DA-125 and ADM markedly retarded the growth of implanted tumor, though they failed to increase mean survival time of tumor-bearing mice. These results suggest that G-CSF is able to not only ameliorate, but reconstitute DA-125-induced myelosuppression without affecting its antitumor potential.
Analgesic Effects of DA-5018, a New Capsaicin Derivative, after Subcutaneous Injection and Topical Application
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 117~124
The analgesic effects of DA-5018, a new caosaucin derivative, were evaluated in various experimental pain models. Drugs were administered subcutaneously or topically. When drugs were administered subcutaneously, 1) the
of DA-5018, morphine . HCI, capsaicin and acetaminophen were 0.091-2.0, 0.3-4.3, 1.4-26.5 and 45.4-643 mg/kg, respectively in various pain or inflammatory models including acetic acid writhing, formalin, tail flick, Randall-Selitto, hot plate and crouton oil-induced ear edema test, 2) the AD2 values (the dose for doubling of pain threshold of vehicle control) of DA-5018, capsaicin and ketoprpgin were 1.07
0. 18, 23.47
4.46 and 2.97
0.43 mg/kg in Freund's complete adjuvant (FCA)-induced arthritic pain model. And by topical application, 1) neither DA-5018 0.3% cream nor Zostrix-HP (capsaicin 0.075%) were effective in formalin test, 2) although DA-5018 0.3% cream significantly inhibited the croton oil-induced ear edema being better than Zostrix-HP and Kenofen (ketoprofen 3%). 3) In FCA model, DA-5018 0.3% cream reversed the decreased pain threshold of arthritic rat from 136.4 g (day 0) to 289.0 g (day 5) and 250.1 g (day 10), which was similar to Zostrix-HP. These results suggest that DA-5018 administered subcutaneously has a potent and broad analgesic spectrum than nonsteroidal antiinflammatory drugs against acute and chronic pain, and by topical application it exerts comparable analgesic and antiinglammaatory effects to capsaicin cream.
[Pt(II)(cis-DACH) (DPPE)] .
: A Novel Class Of Platinum Complex Exhibiting Selective Cytotoxicity to Human Ovarian Carcinoma Cell Lines and Normal Kidney Cells
Jung, Jee-Chang ; Chu, Min-Ho ; Chang, Sung-Goo ; Lee, Kyung-Tae ; Rho, Young-Soo ;
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 125~132
Cisplatin, a platinum-complex, is currently one of the most effective compounds used in the treat-ment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. We synthesized new Pt (II) complex analogue containing 1,2-diaminocyclohexane (DACH) as carrier ligand and 1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(cia-DACH)(DPPE)] .
(PC) was synthes-ized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR),
carbon nuclear magnetic resonance (NMR)] .PC demonstrated acceptable and significant antitumor activity against SKOV-3 and OVCAR-3 human ovarian carcinoma cell lines as compared with that of cisplatin. The cytotoxicity of PC in normal cells was found quite less than that of cisplatin using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), (
H)thymidine uptake and glucose consumption tests in rabbit renal proximal tubular cells, human renal cortical cells and tissues. In conclusion, PC is considered to be more selective cytotoxicity toward human ovarian cancer cells than normal human/rabbit kidney cells.
Four-week Oral Toxicity Study of DA-5018, a New non-narcotic Analgesic Agent
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 133~149
4-week repeated dose toxicity of DA-5018, a new capsaicin analogue analgesic agent, was examined in 5D rats at dosage levels of 0,0.4,2, 10 and 50 mg/kg/day. DA-5018 was administered orally to 17 males and 17 females per group at doses of 0, 10 and 50 mg/kg and to 12 males and 12 females per group at doses of 0.4 and 2 mg/kg. After the administration period, 5 males and 5 females at the 0, 10 and 50 mg/kg were placed on withdrawal for 2 weeks. Treatment-related clinical signs were observed at 10 and 50 mg/kg. Clinical signs observed immediately after the administration of DA-5018 were grooming, sedation or depression, lacrimation, atacia, reddening of extremities and ears, ventral or lateral recumvincy, respiratory distress, cyanosis and convulsion. Delayed-type clinical signs including focal scabbing and depilation around nose were also observed 1 or 2 weeks after the start of administration of DA-5018. Only at the 50 mg/kg group, corneal opacities, reduced body weight gain (male) and death (male 6/17, female 3/17) were noted. In blood biochemical analysis, serum levels of glucose and triglyceride decreased at 10 and 50 mg/kg. In hematological examination, there were increases in the number of red blood cell, hemoglobin content and percent of hematocrit at 10 and 50 mg/kg. Pulmonary enlargement and hemorrhagic spot, focal scabbing and depilation around nose and corneal opacities were seen at the necropsy of the animals died during the dosing of DA-5018 50 mg/kg. Focal scabbing and depilation around nose were observed in the animals terminally necropsied at doses of 10 and 50 mg/kg. Histopathological examination revealed pulmonary hemorrhage, focal necrosis in the scabbed area, corneal necrosis, fibrosis and neovasculization in the stroma. At 0.4 and 2 mg/kg, there were no significant toxic changes attributable to the administration of DA-5018. In conclusion, target organs following to 4-week repeated dose of DA-5018 in the rat were determined to be lung, skin and eyes. Definite toxic dose and no-observed-adverse-effect-level (NOAEL) were estimated to be 50 and 2 mg/kg/day, respectively.
Studies on the Local Irritation of DA-5018, a New Capsaicin Derivative
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 150~157
Capsaicin cream has been used to attenuate the pain associated with diabetic neuropathy, rheum-atoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, local irritation, limits the use of it and there is still a need for a new analgesic devoid of this side effect. This study was conducted to compare the local irritant effect of DA-5018, a new capsaicin derivative, with that of capsaicin in various animal models and human beings. Capsaicin, applied topically to the mouse ear, produced dose-dependent increase of ear volume and the frequency of ear scratching behavior in mice. Neither ear volume nor scratching behavior was affected by DA-5018. In eye wiping test of rat, DA-5018 was 10 times less irritant than capsaicin. Capsaicin administered intradermally into the rat paw elicited paw lick/lift response with a potency which was three times that of DA-5018. Zostrix-HP (0.075% capsaicin cream), but not DA-50180.3% cream, increased ear volume of rat and induced thermal hyperalgesia in normal and carrageenan inflamed paws. Six day-treatment of Zostrix-HP failed to develop tolerance against this thermal hyperalgesia. In human beings, Zostrix-HP produced burning sensation and itching in more than 90% of volunteers involved and its maximum irritant effect was significantly higher than that of DA-5018 cream. These results suggest that local irritation and burning sensation produced by DA-5018 is much less than capsaicin.
Effects of Trypsin Inhibitors on Oleic acid Induced Acute Pancreatitis in Dogs
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 158~164
To investigate the effects of trypsin inhibitors, aprotinin and urinary trypsin inhibitor (UTI), on the cute pancreatitis, this study was carried out in dogs of acute pancreatitis induced by oleic acid (0.28 mg/kg). Administration with aprotinin and UTI seemed to have a therapeutic effect on the clinical sign, ultrasonographic finding, histopathologic finding. But in amylase and lipase activity, there were no significant differences among three groups.
Beneficial Effect of DA-9601, an Extract of Artemisiae Herba, on Animals Models of Inflammatory Bowel Disease
Ahn, Byoung-Ok ; Ryu, Byong-Kweon ; Ko, Jun-Il ; Oh, Tae-Young ; Kim, Soon-Hoe ; Kim, Won-Bae ; Yang, Jun-Nick ; Lee, Eun-Bang ; Hahm, Ki-Baik ;
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 165~173
This study was conducted to investigate the effect of DA-9601, an extract of Artemisiae Herba, which is known to possess mucoprotective action either by free radical scavenging effect or increase of mucus secretion, against animal models of inflammatory bowel disease (IBD) induced by trinirobenzene sulfonic acid (TNBS) or other noxious agents. Experimental colitis was induced by intracolonic administration of TNBS in 50% ethanol, or 1 ml of 7% acetic acid solution (AA), by subcutaneous injection of indomethacin (INDO) in rats, or by supplementing drinking water with 5% dextran sodium sulfate (DSS) in albino mice. DA-9601 was treated orally for 4 to 7 days. Animals were euthanized 1 day after the last treatment for morphological and biochemical analysises. All the noxious agents including TNBS, AA, INDO and DSS elicited severe colitis. The animals treated with DA-9601 showed a consistent, dose-related reduction in the severity of colitis, grossly and histologically. The reduction was significant (p<0.05) after administration of DA-9601 at dose range of 10 mg/kg or above. In TNBS-induced colitis, the rats receiving DA-9601 showed significantly decreased mucosal myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBA-RS), when compared to control and mesalazine groups. Mucosal proinflammatory cytokine levels were also decreased after DA-9601 treatment. In conclusion, DA-9601 ameliorated macroscopic and histologic scores in experimental colitis either through decreasing oxidative stress or by attenuating cytokines involved in inflammation. DA-9601 could be a promising drug for the therapy of IBD.
Immunotoxicity Study of Combined Vaccine (KGCC-95Vl) against Japanese Encephalitis and Hantaan Virus Infection in Guinea Pigs
Shin, Kwang-Soon ; Kim, Chul-Joong ; Yun, Hyo-In ; Shin, Hyeong-Soon ; Park, Jong-Il ; Cha, Shin-Woo ; Oh, Kyu-Ho ; Song, Dong-Ho ; Ahn, Chang-Nam ;
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 174~178
The immnunogenicity of the possible non-essential component of the combined vaccine (KGCC-957) for the prophylaxis against Japanese encephalitis and Hantaan virus infection recently developed by Korea Green Cross Corporation was investigated using the Hartley guinea pigs. The KGCC-95Vl was administered to the guinea pigs subcutaneously to sensitize the animals. The guinea pigs did not induce any anaphylactic immune responses which could be detectable by the active systemic anaphylaxis (ASA), the passive systemic anaphylaxis (PSA), and the passive cutaneous anaphylaxis (PCA) tests. The KGCC-95Vl is considered not to induce any anaphylactic immune responses except the prophylatic immune effects of the vaccine.
Pharmacokinetics and Tissue distribution of DWP20373, a Novel Fluoroquinolone, in Rats and Beagle Dogs
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 179~186
The pharmacokinetics and tissue distribution of DWP20373, a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20373 in plasma, tissue, and urine was performed by both HPLC and microbiological assay. The plasma drug concentration declined biexponentially both rats and beagle dogs. In the rats, the terminal drug elimination half-life (t
/) was 64 min (IV) and 57 min (PO) by bioassay, and 76 min (IV) and 77 min (PO) by HPLC. Whereas in beagle dogs, t
/ was 196 min (IV) and 350 min (PO). The volume of distribution at steady-state (Vd
) was 811 ml/kg (bioassay) and 2061 ml/kg (HPLC) in rats, and 2738 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl
) of DWP20373 was 10 ml/min/kg (bioassay) and 7 ml/min/kg (HPLC) in rats, and 11 m1/min/kg (bioassay) in beagle dogs. The extent of bioavailability after oral administration was 49% (bioassay) and 67% (HPLC) in rats, and 84% (bioassay) in beagle dogs. The 24-h urinary recovery, measured by bioassay, was 2.7% after oral dosing and 5.5% after intravenous dosing in rats. Serum protein binding ratio determined at 27g/ml was 78%. This drug was also distributed in tissues in the decreasing order of liver, kidney, spleen, lung, heart, and muscle determined at 30 min after oral administration.on.
Jn vivo and Jn vivo Antibacterial Activity of DW-ll6, a New Quinolone Antibiotic
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 187~193
The in vivo and in vivo antibacterial activity of DW-116, a newly synthesized fluoroquinolone, were compared with those of other quinolones. DW-116 exhibited more potent antibacterial activity than rufloxacin and lower activity than ofloxacin and ciprofloxacin in in vivo assay But, DW-116 particularly showed strong activity against the family of staphylococci including methicillin-sensitive staphylococcus and its activity was more active than that of ciprofloxacin. The time-kill curve studies showed rapid bactericidal activity for DW-116. The post-antibiotic effect of DW-116 was observed between 0.66 and 5 hours. The therapeutic efficacy of DW-116 against respiratory infection with P. aeruginosa was as strong as that of ciprofloxacin and its effect against urinary tract in(traction with E. coli was more effective than rufloxacin. The excellent therapeutic efficacy of DW-116 against these local infections is due to its good pharmacokinetic profiles.
Hopatoprotective Effects of Extracts form Artemisia iwayomogi
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 194~201
The hepatoprotective activity of six extracts (BE, EE, HH, PS-1, PS-2, KP) from Artimisia iwayomogi was investigated against experimentally produced hepatic damages. Silymarin, DDB and UDCA were used as reference compounds. Treatment with PS-1 extract reduced hepatic demages induced by
, acetaminophen and ANIT but it did not alter ethionine-induced hepatotoxicity In addition, PS-1 extract showed a protective effect against chronic
-induced hepatotoxicity as well as liver regeneration. PS-2 and KP extracts exhibited significant antihepatotoxic effects on D-galactosamine-induced hepatitis. Treatment with EE extract inhibited ethionine-induced fatty liver. These data indicate that the PS-1 extract is the roost hepato-protective constituent and rationalize the traditional use of this plant in hepatobiliary disorders.
Studies on Protective Effect of DA-9601\ulcorner an Artimisiae Herba Extract, against Ethanol-induced Gastric Mucosal Damage and its Mechanism
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 202~210
Protective effect of DA-9601, an extract of Artemisia Herb, against ethanol-induced gastric mucosal injury was evaluated in rats. In the prophylactic study, DA-9601 exhibited total protection (99.4%) against absolute ethanol-induced gastropathy, And the protective effect of DA-9601 lasted up to 2 hours, which was longer than those of other contemporary mucoprotectants. In the treatment study, DA-9601 significantly facilitated the healing of 70% ethanol-induced mucosal damage, which was superior to cetraxate, a commonly used anti-ulcer drug. The mechanisms of mucoprotection of DA-9601 were also assessed. DA-9601 increased the release of prostaglandin E
from murine neutrophils in a dose-dependent manner in vitro. The cytoprotective effect of DA-9601 against ethanol-induced mucosal damage was significantly diminished by the concommitant injection of N
-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, i.v.), a non-specific nitric oxide (NO) synthase inhibitor, while it was not affected by preinjection of indomethacin (5 mg/kg, s.c.), a prostaglandins-depletor. And it was found that DA-9601 significantly enhanced adaptive cytoprotective action of 10% ethanol against absolute ethanol (56.9
6.5 vs 23.0
, p<0.05, mean
SEM), though its exact underlying mechanism remains to be clarified. The present fin[lings demonstrate that DA-9601 exerts gastroprotecticv actions for the stomach against ethanol through several different underlying mechanisms, in which prostanglandins and NO are involved. In conclusion, the results obtained suggest that DA-9601 can be useful both in prevention and treatment of ethanol-induced gastric damage.
The Mechanism of Thermoregulatory Action of Capsaicin Is Different from That of Its Antinociceptive Effect in Guinea Pig
Yi-Sook JUNG ; Tai-Soon CHO ; Shin, Hwa-Sup ;
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 211~214
In the present study, we investigated the mechanisms of antinociceptive effect and thermoregulatory action of capsaicin in guinea pigs. The administration of capsaicin (5 mg/kg, s.c.) caused a significant decrease in frequency of eye wiping, an indicative of nociceptive threshold. This antinociceptive effect of calsaicin was abolished by co-administration of capsazepine (30 mg/kg, s.c.) with capsaicin, suggesting the involvement of a vanilloid receptor in the antinociceptive action of capsaicin. The administration of capsaicin (1 mg/kg, s.c.) produced a significant decrease in body temperature of guinea pigs. The maximum decrease in body temperature by 2 degrees was shown 1 hour after the treatment, and this decrease was not reversed by coadministration of capsazepine. In conclusion, it is suggested that the mechanism of action of capsaicin-induced thermoregulation involves different pathways from that of capsaicin-induced antinociception.
Cytotoxic Effect of Aromatic and Aliphatic Compounds Produced by Streptomyces sp. Isolated in Korea
Biomolecules and Therapeutics, volume 5, issue 2, 1997, Pages 215~221
In an effort to screen new selective antitumor agents from the broth of soil microorganism, cytotoxicity oriented screening was performed against tumor cells and 3 compounds (Compound 1, 2 and 3) were isolated from Sreptomyces parvullus ISP 5048 and their chemical structures were determined. Among these compounds, Compound 2 showed the highest cytotoxicity against P388Dl and L1210. While the
/ values of compound 2 against P388Dl and L1210 were 0.073
g/ml and 0.07
g/ml, respectively, and the
/ value of Compound 3 was 0.17
g/ml against human lung cancer cells, A549, the cytotoxicity of Compound 2 and 3 against normal cell line, Vero E6 cell was about 4- and 8-fold lower than that of adriamycin. Based on the chemical analysis data, Compound 3 was octacosamicine A, a known antibiotic, which was reported by Dobasih et al. (1988). Taken together the results demonstrated that Compound 2 and Compound 3 has the possibility to be developed as antitumor agent because of its potent cytotoxicity as well as high selectivity against various cancer cell lines.