Structure-activity relationships in the Hill inhibitory activity of substituted phenylureas

1987 ◽  
Vol 35 (4) ◽  
pp. 479-483 ◽  
Author(s):  
Patrick Camilleri ◽  
John R. Bowyer ◽  
Terence Gilkerson ◽  
Barbara Odell ◽  
Roger C. Weaver
Keyword(s):  
Inhibitory Activity ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
The Hill

ChemInform Abstract: Structure-Activity Relationships of Biflavonoids for β-Secretase (BACE-1) Inhibitory Activity.

ChemInform ◽  
2013 ◽  
Vol 44 (11) ◽  
pp. no-no
Author(s):  
Hiroaki Sasaki ◽  
Yuki Kitoh ◽  
Kazuhiko Miki ◽  
Kaoru Kinoshita ◽  
Kiyotaka Koyama ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Abstract Structure ◽  
Bace 1

scholarly journals Characterization of platinum(II) complexes exhibiting inhibitory activity against the 20S proteasome

2020 ◽  
Vol 7 (8) ◽  
pp. 200545
Author(s):  
Tatsuto Kiwada ◽  
Hiromu Katakasu ◽  
Serina Okumura ◽  
Akira Odani
Keyword(s):  
Inhibitory Activity ◽  
Chemical Structure ◽  
Competitive Inhibition ◽  
Proteasome Inhibitors ◽  
Platinum Complex ◽  
Platinum Complexes ◽  
Binding Mode ◽  
Structure Activity Relationships ◽  
Structure Activity

Proteasome inhibitors are useful for biochemical research and clinical treatment. In our previous study, we reported that the 4N-coordinated platinum complexes with anthracenyl ring and heterocycle exhibited proteasome-inhibitory activity. In the present study, the structure–activity relationships and characterization of these complexes were determined for the elucidation of the role of aromatic ligands. Lineweaver–Burk analysis revealed that the chemical structure of heterocycles affects the binding mode of platinum complexes. Platinum complexes with anthracenyl ring and pyridine showed competitive inhibition, although platinum complexes with anthracenyl ring and phenanthroline showed non-competitive inhibition. The structure–activity relationships demonstrated that anthracenyl moiety plays a crucial role in proteasome-inhibitory activity. The platinum complexes with naphthyl or phenyl rings exhibited lower inhibitory activities than the platinum complex with anthracenyl ring. The reactivity with N-acetylcysteine varied according to the chemical structure of complexes.

scholarly journals 5'-Nucleotidase inhibitory activity of nucleoticidin, melanocidin A and melanocidin B. Structure-activity relationships.

1985 ◽  
Vol 38 (11) ◽  
pp. 1564-1567 ◽  
Author(s):  
KEIJIRO UCHINO ◽  
HIROSHI OGAWARA ◽  
TETSU AKIYAMA ◽  
AKIRA FUKUCHI
Keyword(s):  
Inhibitory Activity ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals UFLC-MS-IT-TOF and Bioassay Guided Isolation of Flavonoids as Xanthine Oxidase Inhibitors from Diospyros dumetorum

2017 ◽  
Vol 12 (11) ◽  
pp. 1934578X1701201
Author(s):  
Zhen-Tao Deng ◽  
Tong-Hua Yang ◽  
Xiao-Yan Huang ◽  
Xing-Long Chen ◽  
Jian-Gang Zhang ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Folk Medicine ◽  
Hydroxyl Groups ◽  
Active Constituents ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Pulmonary Abscess ◽  
Xanthine Oxidase Inhibitors

Diospyros dumetorum is an important folk medicine for treating pulmonary abscess and inflammation. The leaves of D. dumetorum revealed xanthine oxidase (XOD) inhibitory activity. With the guidance of UFLC-MS-IT-TOF analyses combined with bioassay in vitro, 15 flavonoids were isolated from the active parts of D. dumetorum. Except for 11 (IC50 > 200μM), all compounds showed obvious XOD inhibitory activity with IC50 values of 32.5 ± 0.7 ~ 145.0 ± 3.3 μM. The preliminary structure-activity relationships study suggested that glycosylation on C-3 was unfavorable for XOD inhibitory activity; hydroxyl groups on ring B were essential for maintaining activity; the activity was closely related with the position of galloylation. This is the first recognition of the XOD inhibitory activity and active constituents of D. dumetorum, and will provide valuable information for this plant as a new resource for treating hyperuricemia and gout.

Studies on the novel α-glucosidase inhibitory activity and structure–activity relationships for andrographolide analogues

2006 ◽  
Vol 16 (10) ◽  
pp. 2710-2713 ◽  
Author(s):  
Gui-Fu Dai ◽  
Hai-Wei Xu ◽  
Jun-Feng Wang ◽  
Feng-Wu Liu ◽  
Hong-Min Liu
Keyword(s):  
Inhibitory Activity ◽  
The Novel ◽  
Structure Activity Relationships ◽  
Structure Activity

Structure-Activity Relationships of Biflavonoids for β-Secretase (BACE-1) Inhibitory Activity

Heterocycles ◽  
2012 ◽  
Vol 85 (11) ◽  
pp. 2749 ◽  
Author(s):  
Kunio Takahashi ◽  
Hiroaki Sasaki ◽  
Yuki Kitoh ◽  
Kazuhiko Miki ◽  
Kaoru Kinoshita ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Bace 1

scholarly journals Study on structure–activity relationships (SARs) of epoxylignan compounds with α- glucosidase inhibitory activity

2018 ◽  
Vol 1 (T5) ◽  
pp. 110-115
Author(s):  
Tho Huu Le ◽  
Hai Xuan Nguyen ◽  
Mai Thi Thanh Nguyen
Keyword(s):  
Inhibitory Activity ◽  
Biological Activities ◽  
Stem Bark ◽  
Positive Control ◽  
Polyphenolic Compounds ◽  
Hydroxyl Group ◽  
Epoxy Ring ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Potent Inhibitory Activity

Epoxylignans are polyphenolic compounds, which possess various biological activities such as antiproliferative activity on cancer cells, antioxidant, antihyperglycemic,… In this research, we study on α- glucosidase inhibitory activity of 11 epoxylignans isolated from the stem of Artocarpus heterophyllus, the stem of Willughbeia cochinchinensis, the stem bark of Crateva religiosa, and the propolis of Trigona minor. The results showed that, compounds 1–4 and 7–10 were more potent inhibitory activity than that of positive control acarbose (IC50, 214.5 µM). Based on the results, their structure-activity relationships showed that the presence of the hydroxyl group at C-4, and C-4ʹ positions play an important role in increasing the activity. Furthermore, diepoxylignans having a ketone group at C-9′ exhibited stronger activity. In contrast, the opening of an epoxy ring at C-7 the C-9′ positions reduced the activity.

scholarly journals Assessing Structure-Activity Relationships in FVIII By Integration of Structural, Biophysical, and Biochemical Data Obtained with Anti-FVIII Antibodies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4223-4223 ◽  
Author(s):  
Zhiqian Lucy Liu ◽  
George Bou-Assaf ◽  
Ming Zhang ◽  
Allison Goodman ◽  
Po-lin Chiu ◽  
...  
Keyword(s):  
Human Plasma ◽  
Light Chain ◽  
Inhibitory Activity ◽  
C2 Domain ◽  
Structure Activity Relationships ◽  
Deuterium Uptake ◽  
Negative Stain ◽  
Structure Activity ◽  
Interaction Map ◽  
Hdx Ms

Abstract Introduction Anti-factor VIII (FVIII) antibodies are valuable probes for evaluating structure-activity relationships in FVIII. In this study, we structurally and functionally characterized a panel of anti-FVIII antibodies comprising 36 mouse monoclonal antibodies and 1 camelid nanobody with specificities that span all 5 structural domains of FVIII. Integration of these data into a comprehensive functional interaction map reveals regions that are essential for the function of FVIII and provides a useful guide for researchers engaged in the engineering, quantitation, and purification of FVIII and variants thereof. Materials and Methods Monoclonal mouse IgGs were raised by conventional hybridoma methods or obtained from commercial sources (Green Mountain Antibodies, American Diagnostica). Recombinant B domain-deleted human FVIII (BDD-rFVIII), consisting of a mixture of proteolytically processed forms and dual-chain forms, was generated by transfection of HEK293 cells and purified by immuno-affinity chromatography to >95% purity. Human plasma-derived von Willebrand factor (VWF) was purchased from Haematologic Technologies. The chain and domain specificities of each antibody and competition with VWF for FVIII binding were evaluated by biolayer interferometry (BLI; ForteBio Octet). Pairwise epitope overlap analysis (binning) was performed by both BLI and multiplexed surface plasmon resonance (SPR; BioRad ProteOn). The affinity of each antibody for FVIII was determined by SPR (ProteOn, Biacore T200), and the inhibitory activity of each antibody was determined by the standard Bethesda assay using normal human plasma. The ability of antibodies to inhibit the thrombin-mediated cleavage of FVIII was determined by resolving samples from a digestion time-course on SDS-PAGE and subsequent quantitation by gel densitometry. The morphology of FVIII-Fab fragment complexes was determined by negative stain electron microscopy (EM) with images classified into 25 groups. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to localize antibody epitopes on FVIII by evaluating deuterium uptake in the presence and absence of selected antibodies. Differential deuterium uptake over four hours was evaluated for over 500 unique FVIII-derived peptides that resulted from cleavage with pepsin, with greater than 95% sequence coverage of BDD-FVIII. Results and Conclusions Antibodies in this panel were characterized with respect to FVIII chain and domain specificity. Fifteen antibodies were mapped to the FVIII heavy chain (3 in the A1 domain, 12 in the A2 domain), and 22 antibodies were mapped to the FVIII light chain (8 in A3/C1 domains, 14 in C2 domain). Affinities for FVIII varied widely, with KD values ranging from ~10 nM to ~10 pM. Bethesda inhibitory activities also varied widely, from undetectable levels to greater than 40,000 Bethesda units (BU) per milligram. No correlation was observed between antibody affinity and inhibitory activity, but inhibitory activity was strongly associated with distinct clusters of antibodies having overlapping epitopes. Nine antibodies competed with VWF for binding to FVIII (2 in C1 domain, 7 in C2 domain), and these antibodies were distributed among 3 distinct epitope clusters, indicating that the VWF binding interface is broadly distributed across the C1 and C2 domains. Three C2 domain-specific antibodies that compete with VWF for binding to FVIII also interfered with the liberation of the acidic a3 peptide by thrombin in the absence of VWF. Thrombin-mediated cleavage at other sites in FVIII was not affected by these antibodies, suggesting the presence of a thrombin binding site within the C2 domain that is required specifically for cleavage by thrombin at the N-terminus of the FVIII light chain. The structures of FVIII in complex with 15 individual antibody Fab fragments were determined by negative stain EM for both inhibitory and non-inhibitory antibodies, and precise epitope mapping of selected antibodies was achieved by HDX-MS. Collectively, these data were used to generate an FVIII-antibody interaction map that integrates activity data with structural data spanning the atomic level to the gross morphological level. This integrated map can serve as a resource for the evaluation of structure-activity relationships in FVIII. Disclosures Liu: Biogen Idec: Employment. Bou-Assaf:Biogen Idec: Employment. Zhang:Biogen Idec: Employment. Goodman:Biogen Idec: Employment. Walz:Biogen Idec: Honoraria, Research Funding. Peters:Biogen Idec: Employment. Kulman:Biogen Idec: Employment.

scholarly journals α-Glucosidase Inhibitory Activity of Cycloartane-Type Triterpenes Isolated from Indonesian Stingless Bee Propolis and Their Structure–Activity Relationship

2019 ◽  
Vol 12 (3) ◽  
pp. 102 ◽  
Author(s):  
Niken Pujirahayu ◽  
Debu Kumar Bhattacharjya ◽  
Toshisada Suzuki ◽  
Takeshi Katayama
Keyword(s):  
Inhibitory Activity ◽  
Antioxidant Activities ◽  
Stingless Bee ◽  
Structure Activity Relationships ◽  
Glucosidase Inhibitor ◽  
Structure Activity ◽  
Glucosidase Inhibitors ◽  
Ic50 Values ◽  
New Type ◽  
Treatment Of Diabetes

This study reports on the antioxidant activity and α-glucosidase inhibitory activity of five cycloartane-type triterpenes isolated from Indonesian stingless bee (Tetragonula sapiens Cockerell) propolis and their structure–activity relationships. The structure of the triterpenes was determined to include mangiferolic acid (1), Cycloartenol (2), ambonic acid (3), mangiferonic acid (4), and ambolic acid (5). The inhibitory test results of all isolated triterpenes against α-glucosidase showed a high potential for inhibitory activity with an IC50 range between 2.46 and 10.72 µM. Among the compounds tested, mangiferonic acid (4) was the strongest α-glucosidase inhibitor with IC50 2.46 µM compared to the standard (–)-epicatechin (1991.1 µM), and also had antioxidant activities with IC50 values of 37.74 ± 6.55 µM. The study on the structure–activity relationships among the compounds showed that the ketone group at C-3 and the double bonds at C-24 and C-25 are needed to increase the α-glucosidase inhibitory activity. The carboxylic group at C-26 is also more important for increasing the inhibitory activity compared with the methyl group. This study provides an approach to help consider the structural requirements of cycloartane-type triterpenes from propolis as α-glucosidase inhibitors. An understanding of these requirements is deemed necessary to find a new type of α-glucosidase inhibitor from the cycloartane-type triterpenes or to improve those inhibitors that are known to help in the treatment of diabetes.

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