Structure-Activity Studies in the Class of Endocrine-Active Platinum Complexes and Their Consequence for the Design of New Drugs

1999 ◽  
pp. 427-433
Author(s):  
R. Gust ◽  
R. Keilitz ◽  
K. Schmidt
Keyword(s):  
Platinum Complexes ◽  
New Drugs ◽  
Structure Activity

Biological Activity of Trans-Membrane Anion Carriers

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla
Keyword(s):  
Biological Activity ◽  
Membrane Transport ◽  
Anticancer Agents ◽  
Biological Effects ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Anion Channels ◽  
Cellular Homeostasis ◽  
Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

Review: Studies on the Synthesis of Quinolone Derivatives with Their Antibacterial Activity (Part 1)

2020 ◽  
Vol 24 (8) ◽  
pp. 817-854
Author(s):  
Anil Kumar ◽  
Nishtha Saxena ◽  
Arti Mehrotra ◽  
Nivedita Srivastava
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Properties ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Structure Activity ◽  
Medicinal Properties ◽  
Synthetic Routes ◽  
Quinolone Derivatives

Quinolone derivatives have attracted considerable attention due to their medicinal properties. This review covers many synthetic routes of quinolones preparation with their antibacterial properties. Detailed study with structure-activity relationship among quinolone derivatives will be helpful in designing new drugs in this field.

scholarly journals Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gongming Li ◽  
Qingqing Guo ◽  
Chao Feng ◽  
Huan Chen ◽  
Wenjiao Zhao ◽  
...  
Keyword(s):  
Schistosoma Japonicum ◽  
Inhibitory Activity ◽  
Pyridine Ring ◽  
New Drugs ◽  
Wild Type ◽  
Drug Candidates ◽  
Structure Activity ◽  
Docking Method ◽  
Antigen Protein ◽  
Thioredoxin Glutathione Reductase

Abstract Background Schistosomiasis is a chronic parasitic disease that affects millions of people’s health worldwide. Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR). Methods In this work, one of the oxadiazole-2-oxides derivatives furoxan was used as the lead compound to exploit a series of novel furoxan derivatives for studying inhibitory activity against both recombinant Schistosoma japonicum TGR containing selenium (rSjTGR-Sec) and soluble worm antigen protein (SWAP) containing wild-type Schistosoma japonicum TGR (wtSjTGR), in order to develop a new leading compound for schistosomiasis. Thirty-nine novel derivatives were prepared to test their activity toward both enzymes. The docking method was used to detect the binding site between the active molecule and SjTGR. The structure–activity relationship (SAR) of these novel furoxan derivatives was preliminarily analyzed. Results It was found that several new derivatives, including compounds 6a–6d, 9ab, 9bd and 9be, demonstrated greater activity toward rSjTGR-Sec or SWAP containing wtSjTGR than did furoxan. Interestingly, all intermediates bearing hydroxy (6a–6d) showed excellent inhibitory activity against both enzymes. In particular, compound 6d with trifluoromethyl on a pyridine ring was found to have much higher inhibition toward both rSjTGR-Sec (half-maximal inhibitory concentration, IC50,7.5nM) and SWAP containing wtSjTGR (IC50 55.8nM) than furoxan. Additionally, the docking method identified the possible matching sites between 6d and Schistosoma japonicum TGR (SjTGR), which theoretically lends support to the inhibitory activity of 6d. Conclusion The data obtained herein showed that 6d with trifluoromethyl on a pyridine ring could be a valuable leading compound for further study.

scholarly journals Synthesis andin vitroAntitumor Potency of (Cyclohexane-1,2-Diamine)Platinum(II) Complexes with Aminotris(Methylenephosphonic Acid) as Bone-Seeking Ligand

2005 ◽  
Vol 3 (3-4) ◽  
pp. 179-190 ◽  
Author(s):  
Markus Galanski ◽  
Susanna Slaby ◽  
Michael A. Jakupec ◽  
Bernhard K. Keppler
Keyword(s):  
Dna Adducts ◽  
Coordination Mode ◽  
Carcinoma Cell ◽  
Platinum Complexes ◽  
Ovarian Carcinoma Cell Line ◽  
Aminoacetic Acid ◽  
Structure Activity ◽  
Cellular Processing ◽  
Diamine Ligands

In order to develop platinum complexes with selective activity in primary and secondary bone malignancies and with the aim to optimize antitumor activity, platinum(II) complexes with aminotris(methylenephosphonic acid) as bone-seeking (osteotropic) ligand have been synthesized, characterized and tested in the cisplatin-sensitive ovarian carcinoma cell line CH1. As non-leaving diamine ligands, which are decisive for the cellular processing of DNA adducts,cis-R,S-cyclohexane-1,2-diamine,trans-S,S-cyclohexane-1,2-diamine andtrans-R,R-cyclohexane-1,2-diamine have been used, resulting in complexes 1, 2, and 3, respectively. The cytotoxicity of the complexes under investigation decreases in the order 3>2>1 which is in accord with structure-activity relationships with other (cyclohexane-1,2- diamine)platinum(II) and platinum(IV) complexes: Bothtranscomplexes (2 and 3) display a higherin vitropotency than the correspondingcisisomer (I), with thetrans-R,Risomer (3) being the most active in this series. In comparison to the analogous (cyclohexane-1,2-diamine)platinum(II) complexes with bis(phosphonomethyl)aminoacetic acid as osteotropic carrier ligand, the cytotoxicity of 1-3 was found to be 1.5 – 2 fold higher, which is explainable by a different coordination mode of the phosphonic acid ligands (acetato versus phosphonato).

scholarly journals Thiourea and Guanidine Compounds and their Iridium Complexes in Drug-Resistant Cancer Cell Lines: Structure-Activity Relationships and Direct Luminescent Imaging

2019 ◽  
Author(s):  
Samuel J. Thomas ◽  
Barbora Balonova ◽  
Jindrich Cinatl ◽  
Mark Wass ◽  
Christopher Serpell ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Nature Medicine ◽  
Cancer Cell Lines ◽  
Resistance Mechanisms ◽  
New Drugs ◽  
Iridium Complexes ◽  
Safety Issues ◽  
Structure Activity Relationships ◽  
Structure Activity

<p>Thiourea and guanidine units are found in nature, medicine, and materials. Their continued exploration in applications as diverse as cancer therapy, sensors, and electronics means that their toxicity is an important consideration. We have systematically synthesised a set of thiourea compounds and their guanidine analogues, and elucidated structure-activity relationships in terms of cellular toxicity in three ovarian cancer cell lines and their cisplatin-resistant sub-lines. We have been able to use the intrinsic luminescence of iridium complexes to visualise the effect of both structure alteration and cellular resistance mechanisms. These findings provide starting points for the development of new drugs and consideration of safety issues for novel thiourea- and guanidine-based materials.</p>

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 DESIGN OF COMPOUNDS WITH ANTICONVULSANT ACTIVITY AMONG NMDA-RECEPTOR LIGANDS

2019 ◽  
Vol 19 (1S) ◽  
pp. 225-226
Author(s):  
M A Brusina ◽  
L G Kubarskaya ◽  
V V Iljin ◽  
D N Nikolaev ◽  
L B Piotrovskiy
Keyword(s):  
Immune Responses ◽  
Partition Coefficients ◽  
Structural Parameters ◽  
New Drugs ◽  
Anticonvulsant Effect ◽  
Receptor Ligands ◽  
Structure Activity ◽  
Nmda Receptor Ligands ◽  
General Method

NMDA receptors play an important role in the development of immune responses. Therefore, the design of NMDAergic compounds presents great interest in various areas, including immunology. We have previously shown that some imidazole-4,5-dicarboxylic acid (IDA) derivatives are ligands of these receptors, and can exhibit both agonistic and antagonistic activities. In continuation of these studies and in attempt to establish the main structural parameters that determine the type of the activity, we developed a general method for synthesis of 1-, 2-mono and 1,2-disubstituted IDA derivatives. To establish the structure-activity relationship in the series under investigation, which include about 30 compounds, we try to find correlations of biological activity with the structure of compounds and some their physicochemical parameters (for example, partition coefficients between the lipophilic and hydrophilic phases). Pharmacological analysis in vivo of this set in various models under ip administration showed that a part of them induces a pre-convulsive state in mice of the CBA line, while the other part has a pronounced anticonvulsant effect on the NMDA-induced seizures. Thus, in the series of compounds under investigation substances that are both convulsants and anticonvulsants were found. The results of this study will allow us to design new drugs with anticonvulsant action.

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