Anticancer agents based on Plastoquinone analogs with N-phenylpiperazine: Structure-activity relationship and mechanism of action in breast cancer cells

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.

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Antiproliferative Activity of 8-methoxy Ciprofloxacin-Hydrozone/Acylhydrazone Scaffolds

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200603105644 ◽

2020 ◽

Vol 20 (21) ◽

pp. 1911-1915

Author(s):

Li-Ping Wang ◽

Zhi Xu ◽

Gui-Ying Deng ◽

Sha-Li Xu

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Prostate Cancer Cells ◽

Liver Cancer Cells ◽

Structure Activity ◽

Low Cytotoxicity ◽

Mcf 7

Aims: A series of 8-methoxy ciprofloxacin- hydrazone/acylhydrazone hybrids were evaluated for their activity against a panel of cancer cell lines including HepG2 liver cancer cells, MCF-7, doxorubicin- resistant MCF-7 (MCF-7/DOX) breast cancer cells, DU-145 and multidrug-resistant DU145 (MDR DU-145) prostate cancer cells to seek for novel anticancer agents. Background: Ciprofloxacin with excellent pharmacokinetic properties as well as few side effects, is one of the most common used antibacterial agents. Notably, Ciprofloxacin could induce cancer cells apoptosis, and cell cycle arrest at the S/G2 stage. The structure-activity relationship reveals that the introduction of the methoxy group into the C-8 position of the fluoroquinolone moiety has resulted in a greater binding affinity to the binding site, and 8-methoxy ciprofloxacin derivatives have proved a variety of biological activities even against drug-resistant organisms. However, to the best of our current knowledge, there are no studies that have reported the anticancer activity of 8-methoxy ciprofloxacin derivatives so far. Furthermore, many fluoroquinolone-hydrazone/acylhydrazone hybrids possess promising anticancer activity. Thus, it is rational to screen the anticancer activity of 8-methoxy ciprofloxacin derivatives. Objective: To enrich the structure-activity relationship and provide new anticancer candidates for further investigations. Methods: The desired 8-methoxy ciprofloxacin-hydrazone/acylhydrazone hybrids 5 and 6 were screened for their in vitro anticancer activity against liver cancer cells HepG2, breast cancer cells MCF-7, MCF7/DOX, prostate cancer cells DU-145 and MDR DU-145 by MTT assay. Results: Some of 8-methoxy ciprofloxacin-hydrazone hybrids showed potential activity against HepG2, MCF-7, MCF-7/DOX, DU-145 and MDR DU-145 cancer cell lines, low cytotoxicity towards VERO cells and promising inhibitory activity on tubulin polymerization. Conclusion: Compounds 5d and 5f showed promising anticancer activity, low cytotoxicity, and potential tubulin polymerization inhibitory activity, were worthy of investigation. Other: The structure-activity relationship was enriched.

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

10.21203/rs.3.rs-198850/v1 ◽

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.

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Biological Activity of Trans-Membrane Anion Carriers

Current Medicinal Chemistry ◽

10.2174/0929867325666180309113222 ◽

2018 ◽

Vol 25 (30) ◽

pp. 3560-3576 ◽

Cited By ~ 3

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.

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

Current Medicinal Chemistry ◽

10.2174/0929867326666191016151018 ◽

2019 ◽

Vol 26 ◽

Cited By ~ 1

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.

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