Mapping the melatonin receptor. 2. synthesis and biological activity of indole derived melatonin analogues with restricted conformations of the C-3 amidoethane side chain

Comparison has been made between the activity of the pineal hormone melatonin, and several analogues and metabolites in inhibiting sexual development in a protein-restricted prepubertal rat model. Eleven melatonin analogues or metabolites were tested with the aim of evaluating the model as a test of the hypothesis that melatonin acts as a prohormone and that the ring schism metabolites (kynurenamines) mediate many of the effects attributable to melatonin. Although the hypothesis could not be confirmed, modification of the melatonin structure by lengthening the acylamide side chain or by replacing the 5 methoxy function with fluorine resulted in loss of biological potency. Modification of the melatonin structure to block the two known points of metabolism resulted in no significant alteration in biological activity. Thus 6-chloromelatonin (blocking 6-hydroxylation) and 2,3-dihydromelatonin (blocking oxidative cleavage of the C2-C3 bond) and 6-chloro-2,3-dihydromelatonin remained biologically active. The metabolic products of brain indolearnine-2,3-dioxygenase, N-acetyl-N2-formyl-5-methoxy kynurenamine (aFoMK) and N-acetyl-5-methoxy kynurenamine (aMK), paradoxically were also biologically active.

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Conformationally Restrained Melatonin Analogues: Synthesis, Binding Affinity for the Melatonin Receptor, Evaluation of the Biological Activity, and Molecular Modeling Study

Journal of Medicinal Chemistry ◽

10.1021/jm960651z ◽

1997 ◽

Vol 40 (13) ◽

pp. 1990-2002 ◽

Cited By ~ 53

Author(s):

Gilberto Spadoni ◽

Cesarino Balsamini ◽

Giuseppe Diamantini ◽

Barbara Di Giacomo ◽

Giorgio Tarzia ◽

...

Keyword(s):

Biological Activity ◽

Molecular Modeling ◽

Binding Affinity ◽

Melatonin Receptor ◽

Molecular Modeling Study ◽

Conformationally Restrained ◽

Melatonin Analogues ◽

Modeling Study

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Synthesis and Biological Activity of Brassinosteroid Analogues with a Nitrogen-Containing Side Chain

International Journal of Molecular Sciences ◽

10.3390/ijms22010155 ◽

2020 ◽

Vol 22 (1) ◽

pp. 155

Author(s):

Mikhail V. Diachkov ◽

Karoll Ferrer ◽

Jana Oklestkova ◽

Lucie Rarova ◽

Vaclav Bazgier ◽

...

Keyword(s):

Biological Activity ◽

Functional Groups ◽

Side Chain ◽

Biotic And Abiotic Stresses ◽

Short Side ◽

Arabidopsis Root ◽

Physiological Processes ◽

Growth Promoting ◽

The Impact ◽

Brassinosteroid Analogues

Brassinosteroids are a class of plant hormones that regulate a broad range of physiological processes such as plant growth, development and immunity, including the suppression of biotic and abiotic stresses. In this paper, we report the synthesis of new brassinosteroid analogues with a nitrogen-containing side chain and their biological activity on Arabidopis thaliana. Based on molecular docking experiments, two groups of brassinosteroid analogues were prepared with short and long side chains in order to study the impact of side chain length on plants. The derivatives with a short side chain were prepared with amide, amine and ammonium functional groups. The derivatives with a long side chain were synthesized using amide and ammonium functional groups. A total of 25 new brassinosteroid analogues were prepared. All 25 compounds were tested in an Arabidopsis root sensitivity bioassay and cytotoxicity screening. The synthesized substances showed no significant inhibitory activity compared to natural 24-epibrassinolide. In contrast, in low concentration, several compounds (8a, 8b, 8e, 16e, 22a and 22e) showed interesting growth-promoting activity. The cytotoxicity assay showed no toxicity of the prepared compounds on cancer and normal cell lines.

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Relationship of 25-hydroxyvitamin D3 side chain structure to biological activity.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)42004-8 ◽

1975 ◽

Vol 250 (1) ◽

pp. 226-230

Author(s):

M F Holick ◽

M Garabedian ◽

H K Schnoes ◽

H F DeLuca

Keyword(s):

Biological Activity ◽

Chain Structure ◽

Side Chain ◽

Relationship Of

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Replacement of the interchain disulfide bridge-forming amino acids A7 and B7 by glutamate impairs the structure and activity of insulin

Biological Chemistry ◽

10.1515/bc.2004.151 ◽

2004 ◽

Vol 385 (12) ◽

pp. 1171-1175 ◽

Cited By ~ 7

Author(s):

Zhan-Yun Guo ◽

Xiao-Yuan Jia ◽

You-Min Feng

Keyword(s):

Biological Activity ◽

Disulfide Bonds ◽

Negative Charge ◽

Disulfide Bridge ◽

Site Directed Mutagenesis ◽

Side Chain ◽

Insulin Analogs ◽

High Biological Activity ◽

Chemical Groups ◽

Structure And Activity

Abstract Insulin contains three disulfide bonds, one intrachain bond, A6–A11, and two interchain bonds, A7–B7 and A20–B19. Site-directed mutagenesis results (the two cysteine residues of disulfide A7–B7 were replaced by serine) showed that disulfide A7–B7 is crucial to both the structure and activity of insulin. However, chemical modification results showed that the insulin analogs still retained relatively high biological activity when A7Cys and B7Cys were modified by chemical groups with a negative charge. Did the negative charge of the modification groups restore the loss of activity and/or the disturbance of structure of these insulin analogs caused by deletion of disulfide A7–B7? To answer this question, an insulin analog with both A7Cys and B7Cys replaced by Glu, which has a long side-chain and a negative charge, was prepared by protein engineering, and its structure and activity were analyzed. Both the structure and activity of the present analog are very similar to that of the mutant with disulfide A7–B7 replaced by Ser, but significantly different from that of wild-type insulin. The present results suggest that removal of disulfide A7–B7 will result in serious loss of biological activity and the native conformation of insulin, even if the disulfide is replaced by residues with a negative charge.

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Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

International Journal of Molecular Sciences ◽

10.3390/ijms22041874 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1874

Author(s):

Giarita Ferraro ◽

Alessandro Pratesi ◽

Damiano Cirri ◽

Paola Imbimbo ◽

Daria Maria Monti ◽

...

Keyword(s):

Biological Activity ◽

Diffraction Data ◽

Inductively Coupled Plasma ◽

Emission Spectroscopy ◽

Atomic Emission ◽

Side Chain ◽

Plasma Atomic Emission ◽

Average Amount ◽

X Ray ◽

Inductively Coupled

Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.

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Fluorine substituted methoxyphenylalkyl amides as potent melatonin receptor agonists

MedChemComm ◽

10.1039/c8md00604k ◽

2019 ◽

Vol 10 (3) ◽

pp. 460-464 ◽

Cited By ~ 2

Author(s):

Andrew Tsotinis ◽

Rodanthi Kompogennitaki ◽

Ioannis Papanastasiou ◽

Peter J. Garratt ◽

Alina Bocianowska ◽

...

Keyword(s):

Side Chain ◽

Melatonin Receptor ◽

Receptor Agonists ◽

Methoxy Groups ◽

Melatonin Receptor Agonists

A series of fluorine substituted methoxyphenylalkyl amides were prepared with different orientations of the fluorine and methoxy groups with respect to the alkylamide side chain and with alkyl sides of differing lengths (n= 1–3).

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