Electrochemistry and bioactivity relationship of 6-substituted-4H-Pyrido[4,3,2-kl]acridin-4-one antitumor drug candidates

2012 ◽  
Vol 88 ◽  
pp. 103-109 ◽  
Author(s):  
Laurent Bouffier ◽  
Isabelle Gosse ◽  
Martine Demeunynck ◽  
Pascal Mailley
Author(s):  
Mohammad Abid ◽  
Shailja Singh ◽  
Timothy J. Egan ◽  
Mukesh C. Joshi

Apicomplexian parasite of the genus Plasmodium is the causative agent of malaria, one of the most devastating, furious and common infectious disease throughout the world. According to the latest World malaria report, there were 229 million cases of malaria in 2019 majorly consisting of children under 5 years of age. Some of known analogues viz. quinine, quinoline-containing compounds have been used for last century in the clinical treatment of malaria. Past few decades have witnessed the emergence of multi-drug resistance (MDR) strains of Plasmodium species to existing antimalarials pressing the need for new drug candidates. For the past few decades bioorganometallic approach to malaria therapy has been introduced which led to the discovery of noval metalcontaining aminoquinolines analogues viz. ferroquine (FQ or 1), Ruthenoquine (RQ or 2) and other related potent metal-analogues. It observed that some metal containing analogues (Fe-, Rh-, Ru-, Re-, Au-, Zn-, Cr-, Pd-, Sn-, Cd-, Ir-, Co-, Cu-, and Mn-aminoquines) were more potent; however, some were equally potent as Chloroquine (CQ) and 1. This is probably due to the intertion of metals in the CQ via various approaches, which might be a very attractive strategy to develop a SAR of novel metal containing antimalarials. Thus, this review aims to summarize the SAR of metal containing aminoquines towards the discovery of potent antimalarial hybrids to provide an insight for rational designs of more effective and less toxic metal containing amoniquines.


2020 ◽  
Vol 20 (18) ◽  
pp. 1917-1928
Author(s):  
Denise Rampini ◽  
Diego Campos Prieto ◽  
Ana Luisa Colzi ◽  
Renan Vinícius de Araújo ◽  
Jeanine Giarolla

The Zika virus (ZIKV) infection is a major public health concern in Brazil and worldwide, being a rapidly spreading disease with possible severe complications for pregnant women and neonates. There is currently no preventative therapy or specific treatment available. Within this context, drug repositioning is a very promising approach for the discovery of new treatment compounds, since old drugs may become new ones. Therefore, this paper aims to perform a literature mini-review to identify promising compounds to combat this virus. The mechanism of action at the molecular level and the structure-activity relationship of prototypes are discussed. Among the candidates identified, we highlight sofosbuvir, chloroquine and suramin, which present a greater quantity of experimental data to draw on for our discussion. The current treatment is palliative; therefore, this study is of paramount importance in identifying drug candidates useful for combating ZIKV.


Author(s):  
Hüseyin K. Beker ◽  
Işıl Yıldırım

Background: Heterocyclic compounds play an important role in the pharmaceutical and biological processes. Among all heterocycles, quinolinone/quinoline has one of the most unique structures in the discovery of these compounds. These derivatives have been prepared by various on the structures, positions, and they have attracted a great deal of attention in the field of medicinal chemistry. The great interest to medicinal chemists is the basic scaffold of the fused quinolines derivative. The large road maps of gene and protein expression produced by these methods often can be used to classify cancers or predict responses to certain types of treatments targeting regulated at both the level of transcription and translation and at the level of enzyme activity. These specific regulations may open the door for the discovery of novel drug candidates including an anti-cancer target. Objective: This review will attempt to provide a comprehensive description of different quinolinone derivatives especially by concentrating on compounds containing benzimidazole ring. Quinolones moieties are experimentally proven anticancer pharmacophores. We think these pharmacophore and additional substitutions on these scaffolds would further enhance their activity as anticancer agents. This activity associate with the positioning of these different functional groups, such as fluoro, methoxy, methyl, amino, hydroxy, nitro, bromo, chloro, methylamino, ethoxy, carbonyl, iodo, and trifluoromethyl groups. Among the functional groups, most of the electronwithdrawing groups such as fluoro, chloro, nitro, amino, and carbonyl groups showed stronger activity than those with electron-donating groups such as methyl and methoxy groups. Presence of electron-withdrawing or electron-donating group by varying the quinolinone redox properties affect its capacity of DNA synthesis. Conclusion: The structural motifs attributed to noteworthy inhibitory results have been identified and highlighted in order to encourage further research and develop more efficient. This work to aim to present knowledge and it hoped that this review can be help researchers to explore an interesting quinoline class, and researchers will be able to develop a new vision in the search for rational designs of more powerful, active and less toxic quinoline-based anticancer drugs.


Author(s):  
Andjelka M. Isakovic ◽  
Mirjana B. Čolović ◽  
Tian Ma ◽  
Xiang Ma ◽  
Marija Jeremic ◽  
...  

2016 ◽  
Vol 77 ◽  
pp. 14-19 ◽  
Author(s):  
Ana Marisa Chudzinski-Tavassi ◽  
Katia L.P. Morais ◽  
Mário Thiego Fernandes Pacheco ◽  
Kerly Fernanda Mesquita Pasqualoto ◽  
Jean Gabriel de Souza

2021 ◽  
Vol 22 ◽  
Author(s):  
Dilipkumar Pal ◽  
Souvik Mukherjee ◽  
In-ho Song ◽  
Satish Balasaheb Nimse

: Alzheimer's disease (AD), a chronic neurodegenerative disease, is the most common form of dementia that causes cognitive function impairment, including memory, thinking, and behavioral changes that ultimately lead to death. The over activation of GSK-3, an enzyme from the proline/serine Ki NS family, has been associated with hyper-phosphorylation of tau proteins. Hyper-phosphorylated tau proteins self-assemble to form tangles of straight and helical filaments are known to be involved in AD. Therefore, GSK-3 has been considered a potential target of novel drug discovery for AD treatment. The research on the development of GSK-3 inhibitors has received enormous attention from the vast scientific community because they are targeted for AD and other diseases, including type 2 diabetes, cancers, stroke, Parkinson's disease, bipolar disorder etc. Various drugs originated from synthetic and natural origins have been designed to inhibit GSK-3 activity. However, there is a need to develop novel drug candidates that are selective in the inhibition of GSK3. Hence, this review summarizes the potential of GSK-3 inhibitors for AD therapy. The structure-activity relationship of current drug molecules and the potential problems associated with them are discussed in detail.


Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5667
Author(s):  
Ming-Shu Wang ◽  
Yi Gong ◽  
Zhi-Cheng Yu ◽  
Yan-Guang Tian ◽  
Lin-Sheng Zhuo ◽  
...  

A robust, practical, and scalable approach for the construction of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives 13 via the addition of Grignard reagents to 4-amino-2-chloronicotinonitrile (15) was developed. Starting with various Grignard reagents, a wide range of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives 13 were conveniently synthesized in moderate-to-good yields through addition–acidolysis–cyclocondensation. In addition, the robustness and applicability of this synthetic route was proven on a 100 g scale, which would enable convenient sample preparation in the preclinical development of 1,6-naphthyridin-4-one-based MET-targeting antitumor drug candidates.


2000 ◽  
Vol 274 (2) ◽  
pp. 359-369 ◽  
Author(s):  
Chang-Hun Lee ◽  
Heedouk Hong ◽  
Joon Shin ◽  
Mankil Jung ◽  
Injae Shin ◽  
...  

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