Protection of Murine L1210 Leukemia and Bone Marrow Progenitor Cells Against Mechlorethamine and Inhibition of Choline Uptake as a Structure–Activity Relationship of 2-Dimethylaminoethanol and Its Analogues

1984 ◽  
Vol 73 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Saulius A. Naujokaitis ◽  
Joyce M. Fisher ◽  
Marco Rabinovitz
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Choline Uptake ◽  
L1210 Leukemia ◽  
Bone Marrow Progenitor Cells ◽  
Structure Activity ◽  
Bone Marrow Progenitor ◽  
Relationship Of

scholarly journals Anticancer Activity and Structure Activity Relationship of Non-Symmetrical Choline Kinase Inhibitors

2021 ◽  
Author(s):  
Santiago Schiaffino-Ortega ◽  
Elena Mariotto ◽  
Pilar María Luque-Navarro ◽  
María Kimatrai-Salvador ◽  
Ramon Hurtado-Guerrero ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Kinase Inhibitors ◽  
Structure Activity Relationship ◽  
Inhibitory Effect ◽  
Activity Relationship ◽  
Choline Kinase ◽  
Choline Uptake ◽  
Uptake Inhibition ◽  
Structure Activity ◽  
Relationship Of

Choline kinase inhibitors are an important class of cytotoxic compounds useful for the treatment of different forms of cancer since aberrant choline metabolism is a feature of neoplastic cells. Here we present the characterization and the structure activity relationship of a series of non-symmetrical choline kinase inhibitors characterized by a 3-aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium cationic heads through several linkers. These derivatives were evaluated both for their inhibitory activity on the enzyme and for their antiproliferative activity in a panel of six human tumor cell lines. The compounds with the best inhibitory results were those connected to the linker by the N-atom (4a-h) and these results are supported by docking studies. The compounds with the best antiproliferative results were those connected to the linker by the O-atom (3a-h). On the other hand, as was predictable in both families, the inhibitory effect on the enzyme is greater the shorter the length of the linker, while in tumor cells, lipophilicity and choline uptake inhibition could play a decisive role. Interestingly compounds 3c and 4f, selected for both their ability to inhibit the enzyme and good antiproliferative activity, are endowed with a low toxicity in non-tumoral cells (e.g human peripheral lymphocytes) respect to cancer cells. These compounds were also able to induce to induce apoptosis in Jurkat leukemic cells without causing significative variations of cell cycle. It is worth to mention that these derivatives, beside their inhibitory effect on choline kinase, displayed a modest ability to inhibit choline uptake thus suggesting that this mechanism may also contribute to the observed cytotoxicity.

Structure-activity relationship of (-) mammea A/BB derivatives against Leishmania amazonensis

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
MA Brenzan ◽  
CV Nakamura ◽  
BPD Filho ◽  
T Ueda-Nakamura ◽  
MCM Young ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Leishmania Amazonensis ◽  
Activity Relationship ◽  
Structure Activity ◽  
Relationship Of

Antineoplastic Activity, Structural Modification, Synthesis and Structure-activity Relationship of Dammarane-type Ginsenosides: An Overview

2019 ◽  
Vol 23 (5) ◽  
pp. 503-516 ◽  
Author(s):  
Qiang Zhang ◽  
Xude Wang ◽  
Liyan Lv ◽  
Guangyue Su ◽  
Yuqing Zhao
Keyword(s):  
Structural Modification ◽  
Gastrointestinal Disease ◽  
Structure Activity Relationship ◽  
Cerebrovascular Diseases ◽  
Activity Relationship ◽  
Cycle Arrest ◽  
Structure Activity ◽  
Wide Range ◽  
Structural Association ◽  
Relationship Of

Dammarane-type ginsenosides are a class of tetracyclic triterpenoids with the same dammarane skeleton. These compounds have a wide range of pharmaceutical applications for neoplasms, diabetes mellitus and other metabolic syndromes, hyperlipidemia, cardiovascular and cerebrovascular diseases, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease and other conditions. In order to develop new antineoplastic drugs, it is necessary to improve the bioactivity, solubility and bioavailability, and illuminate the mechanism of action of these compounds. A large number of ginsenosides and their derivatives have been separated from certain herbs or synthesized, and tested in various experiments, such as anti-proliferation, induction of apoptosis, cell cycle arrest and cancer-involved signaling pathways. In this review, we have summarized the progress in structural modification, shed light on the structure-activity relationship (SAR), and offered insights into biosynthesis-structural association. This review is expected to provide a preliminary guide for the modification and synthesis of ginsenosides.

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