A mode of action study of cationic anthraquinone analogs: a new class of highly potent anticancer agents

MedChemComm ◽  
2015 ◽  
Vol 6 (11) ◽  
pp. 2012-2022 ◽  
Author(s):  
Jaya P. Shrestha ◽  
Yagya Prasad Subedi ◽  
Liaohai Chen ◽  
Cheng-Wei Tom Chang
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Mode Of Action ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
New Class ◽  
Structure Activity ◽  
Sar Study

Previously, we reported the synthesis and structure–activity relationship (SAR) study of a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium salts, which had very potent anti-proliferative activities (low μM to nM GI50) against a broad range of cancer cells.

scholarly journals Lead optimization of novel quinolone chalcone compounds by a structure-activity relationship (SAR) study to increase efficacy and metabolic stability

2021 ◽  
Author(s):  
James Knockleby ◽  
Aicha Djigo ◽  
I. Kalhari Lindamulage ◽  
Chandrabose Karthikeyan ◽  
Piyush Trivedi ◽  
...  
Keyword(s):  
Binding Site ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Cancer Drug ◽  
Multi Drug Resistance ◽  
Cancer Cell Death ◽  
Colchicine Binding Site ◽  
Structure Activity

Abstract Many agents targeting the colchicine binding site in tubulin have been developed as potential anticancer agents. However, none has successfully made it to the clinic, due mainly to dose limiting toxicities and the emergence of multi-drug resistance. Chalcones targeting tubulin have been proposed as a safe and effective alternative. To identify the most effective anticancer chalcone compound, we synthesized 17 quinolone-chalcone derivatives based on our previously published CTR-17 and CTR-20, and then carried out a structure-activity relationship study. We identified two compounds, CTR-21 [((E)-8-Methoxy-3-(3-(2-methoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one)] and CTR-32 [((E)-3-(3-(2-ethoxyphenyl)-3-oxoprop-1-enyl) quinolin-2(1H)-one)] as potential leads, which contain independent moieties that play a significant role in their enhanced activities. At the nM range, CTR-21 and CTR-32 effectively kill a panel of different cancer cells originated from a variety of different tissues including breast and skin. Both compounds also effectively kill multi-drug resistant cancer cells. Most importantly, CTR-21 and CTR-32 show a very high degree of selectivity against cancer cells. In silico, both of them dock near the colchicine-binding site with similar energies. However, only CTR-21 effectively prevents tubulin polymerization, leading to the cell cycle arrest at G2/M and, eventually, cancer cell death by apoptosis. Perhaps not surprisingly, the combination of CTR-21 and ABT-737, a Bcl-2 inhibitor, showed synergistic effect in killing cancer cells, since we previously found the “parental” CTR-20 also exhibited synergism. Taken together, CTR-21 can potentially be a highly effective and relatively safe anti-cancer drug.

scholarly journals Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study

RSC Advances ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. 4763-4775 ◽  
Author(s):  
Changliang Xu ◽  
Xiaoguang Bai ◽  
Jian Xu ◽  
Jinfeng Ren ◽  
Yun Xing ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase B ◽  
Structure Activity Relationship ◽  
Crotonic Acid ◽  
Activity Relationship ◽  
New Class ◽  
Structure Activity ◽  
Sar Study

Structure–activity relationship (SAR) study of a series of unsaturated crotonic acid derivatives as potential PknB inhibitors.

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.

Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

2019 ◽  
Vol 26 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Danuta Drozdowska
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Physicochemical Characterization ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Biological Research ◽  
Structure Activity ◽  
Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

Triazol: a privileged scaffold for proteolysis targeting chimeras

2019 ◽  
Vol 11 (22) ◽  
pp. 2919-2973 ◽  
Author(s):  
Li-Wen Xia ◽  
Meng-Yu Ba ◽  
Wei Liu ◽  
Weyland Cheng ◽  
Chao-Ping Hu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Anticancer Activity ◽  
Mode Of Action ◽  
Critical Analysis ◽  
Enzyme Inhibitors ◽  
Structure Activity Relationship ◽  
Target Protein ◽  
Activity Relationship ◽  
Structure Activity ◽  
Privileged Scaffold

Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC. Some PROTACs with a triazole linker have displayed promising anticancer activity. This review provides an overview of PROTACs with a triazole scaffold and discusses its structure–activity relationship. Important milestones in the development of PROTACs are addressed and a critical analysis of this drug discovery strategy is also presented.

Structure-Activity Relationship Analyses of Glycyrrhetinic Acid Derivatives as Anticancer Agents

2011 ◽  
Vol 11 (10) ◽  
pp. 881-887 ◽  
Author(s):  
B. Lallemand ◽  
M. Gelbcke ◽  
J. Dubois ◽  
M. Prevost ◽  
I. Jabin ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Structure Activity Relationship ◽  
Glycyrrhetinic Acid ◽  
Activity Relationship ◽  
Structure Activity
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