Biomedical subjects

H P Kim

Publications and source records attributed to H P Kim.

18 recordsLinked to original sources

PubMed1995

Suppression of mouse lymphocyte proliferation in vitro by naturally-occurring biflavonoids.

In a continuing effort to investigate biological activities of flavonoids, nine biflavonoids, isolated from three plant sources were evaluated for their suppressive effects on mouse lymphocyte proliferation. The biflavonoids tested were amentoflavone, bilobetin, ginkgetin, isoginkgetin, sciadopitysin, ochnaflavone, 4'-O-methylochnaflavone, cryptomerin B and isocryptomerin. At 10 uM, several biflavonoids such as ginkgetin, isoginkgetin, ochnaflavone, cryptomerin B and isocryptomerin showed the suppressive activity against lymphocyte proliferation induced by Con A or LPS. Apigenin (flavone) and quercetin (flavonol) were suppressive against Con A-induced lymphocyte proliferation, but not against LPS-induced lymphocyte proliferation at the same concentration range. Biflavonoids were found to be irreversible inhibitors of lymphocyte proliferation. This is the first report describing the suppressive effects of naturally-occurring biflavonoids against lymphocyte proliferation.

Animals↗

PubMed1992

Anticlastogenic effect of flavonoids against mutagen-induced micronuclei in mice.

14 flavonoids, including flavone and flavonol derivatives, were tested for their anticlastogenic effect against induction of micronuclei by benzo[a]pyrene in polychromatic erythrocytes of mice. When each flavonoid was administered orally, together with intraperitoneally administered benzo[a]pyrene, most flavonol derivatives showed an anticlastogenic effect. The data suggest that the 2,3-double bond and 3,5,7-hydroxyl groups in the flavonoid molecules may be essential to produce anticlastogenic effects against benzo[a]pyrene. Galangin, one of the active compounds, and (-)-epicatechin, a weak one, were administered to mice in order to compare their anticlastogenic effect against 3 different kinds of carcinogens: ethyl methanesulfonate, 7,12-dimethylbenz[a]anthracene, and adriamycin. Galangin showed a stronger anticlastogenic effect than (-)-epicatechin against ethyl methanesulfonate and 7,12-dimethylbenz[a]anthracene. However, there was no significant effect against adriamycin-induced micronuclei by both compounds. Our study indicates that most flavonoids are anticlastogenic agents. Their anticlastogenic effects are apparently independent of their own clastogenic activities. Furthermore, their anticlastogenic activities do not apply universally to all types of genotoxic chemicals.

Animals↗

PubMed1992

New anti-inflammatory antedrugs: steroid acid esters and amides.

Therapeutic use of anti-inflammatory steroids is limited, due primarily to their suppressive effects on pituitary function and the immune system. In an attempt to circumvent the untoward systemic effects of corticosteroids, a new approach, the antedrug concept, was formulated by Lee. The term "antedrug" describes a drug that is active upon local application but is easily biotransformed, on entry into the systemic circulation, to an inactive or much less active metabolite. Thus, an antedrug acts only locally at the site of application and produces minimal systemic effects. This report provides a synopsis of the "evolution" of steroidal antedrugs, containing a metabolically labile carboxamide moiety, on the side-chain or at the C-16 position of prednisolone. Pharmacological screening of these steroidal antedrugs in the rat cotton pellet and croton oil-induced ear oedema bioassays led to the identification of P16CM, 11, as the lead compound and a viable drug candidate.

Amides↗

PubMed1991

Synthesis and pharmacological evaluation of new topical anti-inflammatory steroids.

The purpose of this research was to develop new topical steroid derivatives showing reduced systemic effects. Pregna-16 alpha,17-carboxycyclic acetal derivatives have been recently synthesized by reacting triamcinolone with methyl acetylalkanoate in the presence of a catalytic amount of perchloric acid. In testing for the anti-inflammatory activity of the compounds, rat cotton-pellet granuloma inhibition bioassay and mouse croton-oil-induced ear oedema inhibition bioassay were employed. One of the synthesized compounds, (22R)-9 alpha-fluoro-11 beta,21-dihydroxy-3,20-dioxo-16 alpha, 17-(methyl, methoxycarbonylmethyl)methylenedioxy-1,4-pregnadiene (I), showed more or less the same activity as shown by prednisolone in the granuloma inhibition test. However, compound I showed higher activity in the ear oedema inhibition test when applied topically (ID50 = 0.002 mg), as compared to prednisolone (ID50 = 0.006 mg) and triamcinolone (ID50 = 0.026 mg). When compound I was applied to mice, and thymus involution was measured for judging systemic effects, it was found that compound I did not show any significant thymus involution up to 0.1 mg/mouse (systemic administration) and 0.5 mg/mouse (topical administration). Because of its significantly reduced systemic effects, this compound is a promising topical anti-inflammatory steroid.

Administration, Topical↗

PubMed1989

A novel class of local antiinflammatory steroids. 2nd communication: pharmacological studies of methyl 11 beta,17 alpha,21- trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate and methyl 11 beta,21-dihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate.

Two novel 16-substituted steroidal carboxylate esters derived from prednisolone, methyl 11 beta,17 alpha,21- trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate (P16CM) and methyl 11 beta,21-dihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha- carboxylate (DeoxyP16CM) were evaluated for in vivo antiinflammatory and glucocorticoid activities. Results indicate that incorporation of a methoxycarbonyl group at the 16 position of prednisolone, as in P16CM, resulted in 5.5 times more local activity in the cotton pellet granuloma assay and 14 times more topical activity in the croton oil induced ear edema bioassay as compared with the parent compound prednisolone (P). The 17 alpha-dehydroxy analogue of P16CM (DeoxyP16CM) retained one-half the local activity of P in the cotton pellet granuloma bioassay and topical activity equal to P in the croton oil induced ear edema bioassay. Favorable dissociation of local from systemic effects is seen for these steroidal 16-carboxylate esters since their systemic antiinflammatory activity was significantly less than that of P, and their suppression of plasma corticosterone and ACTH levels was minimal. While P16CM does exhibit some thymolytic activity, DeoxyP16CM is essentially devoid of thymus atrophogenic effects at equiactive doses. Thus, these compounds may represent safer topical therapeutic agents.

Administration, Topical↗

PubMed1989

A novel class of local antiinflammatory steroids. 1st communication: analogues of methyl 11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate.

A novel class of steroidal 16-esters and amides, 1-8 has been synthesized and evaluated as safer local antiinflammatory agents. These compounds retain the intact ketol side-chain of prednisolone and have an alkanoate ester or carboxamide function at the C-16 of the steroid nucleus. In the cotton pellet granuloma assay a correlation was observed between the size of the C-16 substituent group and the local antiinflammatory activity. The incorporation of a methyl carboxylate group at the C-16 position of prednisolone as in methyl 11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate, 5, resulted in an increase in antiinflammatory activity. The 17-deoxy analogue of 5, 1, retained one-half the activity of prednisolone. These two compounds were further evaluated for their effects on plasma corticosterone, adrenal and thymic weights at their ID50 doses for granuloma formation. Neither 5 nor 1 depressed plasma corticosterone levels or significantly altered adrenal weights. Compound 1 was also devoid of thymolytic activity, whereas 5 produced a 33% thymic involution at its ID50 compared to 47% for prednisolone at its equiactive dose.

Adrenal Glands↗

PubMed1987

Synthesis of new antiinflammatory steroidal 20-carboxamides: (20R)- and (20S)-21-(N-substituted amino)-11 beta,17,20-trihydroxy-3,21-dioxo-1,4- pregnadiene.

The synthesis and antiinflammatory activities of new steroidal 20-carboxamides, (20R)- and (20S)-21-(N-substituted amino)-11 beta,17,20-trihydroxy-3,21-dioxo-1,4-pregnadiene are described. These compounds were prepared from the respective isomer of 20-dihydroprednisolonic acid, (20R)- and (20S)-11 beta,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oic acid, by coupling with primary amines after the activation of the steroid acid with N,N1-dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole. Confirmation of the configurational assignment at C-20 of the 20-carboxamides was achieved by reduction of methyl (20R)- and (20S)-11 beta,17,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate to the known stereochemistry at C-20 of (20R)- and (20S)-11 beta,17,20,21-tetrahydroxy-3-oxo-1,4-pregnadiene The topical antiinflammatory activities of these steroidal 20-carboxamides were assessed by the croton oil induced ear edema assay and their local and systemic antiinflammatory activities by the cotton pellet granuloma bioassay. Results of these investigations suggest a structure-activity relationship where carboxamide derivatives with the 20(R)-hydroxy configurations exhibit higher potency than those with the 20-(S)-hydroxy configurations. The amides of steroidal 21-oic acids with high local antiinflammatory potency exhibited systemic activities unlike the corresponding esters of steroidal 21-oic acids, which are devoid of systemic activities.

Animals↗

PubMed1986

Topical anti-inflammatory activity of esters of steroid 21-oic acids.

Prednisolone derivatives, methyl 20 alpha- and 20 beta-dihydroprednisolonate and methyl 17,20 alpha- and 17,20 beta-acetonidodihydroprednisolonate have been evaluated for their topical anti-inflammatory activity in the croton oil induced ear edema test. The order of anti-inflammatory potency was prednisolone greater than methyl 17,20 alpha-acetonidodihydroprednisolonate greater than methyl 17,20 beta-acetonidodihydroprednisolonate greater than methyl 20 beta-dihydroprednisolonate greater than methyl 20 alpha-dihydroprednisolonate. This order was paralleled by the compounds' octanol-aqueous partition coefficients. Furthermore, after two consecutive days topical administration of an equipotent anti-inflammatory dose, only prednisolone significantly decreased plasma corticosterone levels and relative thymus weight, while the new steroid derivatives had no effect on these parameters, indicating their lack of systemic side effects.

Administration, Topical↗

PubMed1984

Anti-inflammatory activity of the epimers of N-propyl 20 xi-dihydroprednisolonamide.

The epimers of a steroid carboxamide, N-propyl 20 alpha- and 20 beta -dihydroprednisolonamide, were evaluated for their local and systemic effects on granuloma formation, pituitary-adrenal function and liver glycogen content in rats. When the carboxamides were administered locally, the 20 beta-epimer exhibited greater activity than the 20 alpha-epimer in suppressing cotton pellet granuloma formation. Neither epimer had suppressive effects on thymus weight and plasma corticosterone levels at the dose level used. When the carboxamides were administered systemically, they were pharmacologically inactive. Furthermore, in acute pharmacological studies, the carboxamides neither increased tyrosine aminotransferase activity and glycogen deposition in the liver nor decreased plasma corticosterone levels and relative thymus weight.

Adrenal Glands↗

PubMed1983

Immobilization of urokinase on agarose matrices.

Immobilization of urokinase, a plasminogen activator, was carried out to determine the effect of spacer length used on the immobilized enzyme activity. The enzyme was covalently coupled to agarose gel, both directly to the matrix and also via interposing different lengths of spacer groups. The specific activity of immobilized urokinase increased as the spacer length (n') increased to a certain length and tended to decrease thereafter. The maximal activity was shown when the value of n' was 7 for the agarose-NH-(CH2)n-CO-NH-(CH2)2-CO-NH-urokinase series. The coupling yield of the enzyme activity was from 33 to 68% depending on various forms of immobilized urokinase. The immobilized urokinase was characterized with regard to pH, temperature, storage, and thermal stabilities.

Endopeptidases↗

PubMed1983