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Biomedical subjects

I Moriguchi

Publications and source records attributed to I Moriguchi.

At least 19 recordsLinked to original sources
PubMed1992

Structure-activity studies of 3-benzoylpropionic acid derivatives suppressing adjuvant arthritis.

3-Benzoylpropionic acid derivatives possess an immunomodulative activity and suppress adjuvant arthritis. To understand how substituents affect the biological activity, the quantitative structure-activity relationships of 30 compounds were analyzed by the adaptive least-squares method. For the suppressing activity in rats, the electronic effects and the structural feature of the substituent on benzene ring were suggested to be important. To reinforce and confirm the correlation, 4 additional compounds of phenoxybutyric acid derivatives were synthesized and tested with the rat adjuvant-induced arthritis. These compounds were found to have potent suppressing activity.

Animals↗
PubMed1990

Quantitative structure-activity relationships for calmodulin inhibitors.

Using the discriminant analysis method, we completely distinguished 24 calmodulin inhibitors in three groups, as classified by Zimmer et al. The resultant discriminant functions distinguished the three groups in terms of positive potential surface area on the side chain, as well as the total and neutral surface areas on the ring in the inhibitor molecules. Group assignment of additional calmodulin inhibitors from other sources was then estimated according to the discriminant functions. The relationship between structure and inhibitory potency on calmodulin-activated phosphodiesterase for group I inhibitors, together with those estimated, was studied using the adaptive least squares method with several parameters dependent on molecular conformations. A "best conformer" was selected for each inhibitor on the basis of quantitative structure-activity relationship (QSAR). The results of QSAR analysis of group I inhibitors showed that hydrophobicity was important for the ring moiety but not for the side chain. The negative potential surface area of the side chain is necessary for activity. It is desirable for the nitrogen atom in the side chain, which is considered the center of the negative potential area, to be located far from the ring moiety. Thus, the ring moiety and side chain may possibly play different roles in interactions with the receptor system.

Calmodulin↗
PubMed1990

Fuzzy adaptive least squares and its use in quantitative structure-activity relationships.

Fuzzy adaptive least squares (FALS), a pattern recognition method designed to correlate molecular structure with activity rating, has been developed. A novel feature of FALS is that the degree to which each sample belongs to an activity class is given using a membership function. The algorithm involves an iterative modification of forcing factors to maximize the sum of the membership function values over all samples. This paper first describes the method and calculation procedure of FALS89 (1989 version of FALS), and then shows its application to the correlation of structure with a potency rating of anticarcinogenic mitomycin derivatives and arginine-vasopressin antagonists. FALS89 applied to these samples showed considerably high reliability in both recognition and leave-one-out prediction.

Antibiotics, Antineoplastic↗
PubMed1990

Inhibitory activity and protein binding of L-lysine derivatives as angiotensin converting enzyme inhibitors.

Four compounds 1a-4a containing one L-lysine residue in the molecule including a diastereomer mixture of lisinopril (N-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline) and N epsilon-carbobenzoxy-L-lysine derivatives 1b-4b of each of the four compounds were synthesized to compare the angiotensin converting enzyme (ACE) inhibitory activities in vitro and in vivo. They all showed high ACE inhibitory activity in vitro (IC50 = 0.14-42 nmol/l). A marked difference, however, was observed in inhibition of the pressor response to angiotensin I between 1a-4a (high activity) and 1b-4b (low activity). The binding of these compounds to human serum proteins in vitro was investigated by means of equilibrium dialysis and ultracentrifugation. Compounds 1b-4b showed higher levels of binding to serum albumin than that of the corresponding compounds 1a-4a, and the percentage of binding ranged from 20.1 to 89.1%. Furthermore, the inhibitory activity of compounds 1b-4b in vitro was decreased by the addition of albumin in a concentration-dependent manner. These results suggested that the difference in the protein binding rate of compounds is one of the important factors influencing the inhibitory activity in vivo.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Binding of pyrene-1-butyric acid to serum albumin: species differences.

Changes of the fluorescence spectra and quantum yield of pyrene-1-butyric acid (PYB) induced by rat (RSA), horse (HoSA), and pig serum albumins (PSA) and rat serum were compared at pH 7.4. RSA and rat serum caused marked quenching of the PYB fluorescence. On the contrary, HoSA and PSA increased the fluorescence intensity. In RSA and rat serum solutions, the PYB fluorescence intensity due to monomer emission was greatly diminished, and an additional emission due to excimer formation appeared at 480 nm. On the other hand, in the case of HoSA and PSA solutions, monomer emission gave rise to high fluorescence intensity and no excimer formation was observed. The binding parameters of PYB to RSA, HoSA, and PSA as well as human (HSA), bovine (BSA), rabbit (RbSA) and dog serum albumins (DSA) were compared by equilibrium dialysis method. The primary binding site affinity was in the order RSA greater than HSA greater than HoSA greater than RbSA greater than DSA greater than or equal to BSA greater than PSA. However, for RSA and HSA, which showed reduced monomer emission and clear excimer fluorescence, the primary binding site number (n1) was 2.71 and 2.90, respectively, considerably greater than those values for the other serum albumins. These findings suggest that PYB binds to RSA and HSA as a dimer. On the other hand, PYB appears to bind with BSA, RbSA, DSA and HoSA as a monomer. The primary binding site was not clearly recognized in PSA, which showed little enhancement of fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Synthesis and quantitative structure-activity relationship analysis of N-triiodoallyl- and N-iodopropargylazoles. New antifungal agents.

New series of N-(2,3,3-triiodoallyl) and N-(3-iodopropargyl) azole derivatives (100 compounds) involving pyrrole, pyrazole, imidazole, triazole, and tetrazole nuclei were synthesized successively with the aid of quantitative structure-activity relationship (QSAR) analysis to obtain potent antifungal agents. Starting from the derivatives of nitropyrrole-containing antibiotics, the QSAR analysis of the pyrrole derivatives against Candida albicans and Trichophyton mentagrophytes strains indicated the positive contribution of the nitro group and negative effect of the size of molecule. Further application of the QSAR analysis on the multi-azole derivatives revealed the importance of hydrophobicity and electronegativity as well as steric effect to the activities and led to the synthesis of one of the most potent iodo compounds, 2-(2,3,3-triiodoallyl)tetrazole (67, ME1401).

Allyl Compounds↗
PubMed1986

Albumin-induced changes of fluorescence spectra of 1-pyrenebutyric acid.

Changes in the fluorescence spectra and quantum yield of 1-pyrenebutyric acid (1) induced by human, bovine, rabbit, and dog serum albumins and healthy adult serum, liver-disease patient serum, and renal-disease patient serum were compared at pH 7.4. Human serum albumin, healthy adult serum, and liver-disease patient serum caused marked quenching of the fluorescence of 1-pyrenebutyric acid. On the contrary, bovine, rabbit, and dog serum albumins increased the fluorescence intensity. Renal-disease patient serum also enhanced the intensity but caused quenching of the fluorescence after treatment with charcoal. Thus, 1-pyrenebutyric acid clearly shows interspecies differences in the environment or the structure of the binding site on serum albumin between humans and other animals. Furthermore, it is suggested that some substance which influences the character of the binding site for 1-pyrenebutyric acid exists in the serum of renal-disease patients.

Animals↗
PubMed1986

Structure-activity studies of 4,6-disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives with analgesic and antiinflammatory activities.

4,6-Disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives showed analgesic and antiinflammatory activities when assayed by the acetic acid writhing test in mice and the carrageenin edema test in rats. To understand how the substituents affect the biological activities, the quantitative structure-activity relationships (QSAR) of 38 compounds were analyzed using the adaptive least-squares method (ALS method). The resulting QSAR suggested that some chemical modifications of 4,6-disubstituted furo[3,2-b]indole derivatives would improve their biological activities. Thus, 15 additional compounds were synthesized to reinforce and confirm the correlation. Among these compounds, particularly 4-(2-ethylhexanoyl)-2-(morpholinocarbonyl)-6-(trifluoromethy l) furo[3,2-b]indole showed pronounced biological activities. This compound gave a pharmacological activity spectrum similar to that of tiaramide but exhibited much higher potency.

Animals↗