Pyrimidine-fused Dinitrogenous Penta-heterocycles as a Privileged Scaffold for Anti-Cancer Drug Discovery

Author(s):  
Wen Li ◽  
Jinyang Zhang ◽  
Min Wang ◽  
Ru Dong ◽  
Xin Zhou ◽  
...  

Abstract: Pyrimidine-fused derivatives that are the inextricable part of DNA and RNA play a key role in the normal life cycle of cells. Pyrimidine-fused dinitrogenous penta-heterocycles including pyrazolopyrimidines and imidazopyrimidines is a special class of pyrimidine-fused compounds contributing to an important portion in anti-cancer drug discovery, which have been discovered as core structure for promising anti-cancer agents used in clinic or clinical evaluations. Pyrimidine-fused dinitrogenous penta-heterocycles have become one privileged scaffold for anti-cancer drug discovery. This review consists of the recent progress of pyrimidine-fused dinitrogenous penta-heterocycles as anti-cancer agents and their synthetic strategies. In addition, this review also summarizes some key structure-activity relationships (SARs) of pyrimidine-fused dinitrogenous penta-heterocycle derivatives as anti-cancer agents.

2020 ◽  
Vol 17 (9) ◽  
pp. 1102-1116
Author(s):  
Sudip Kumar Mandal ◽  
Utsab Debnath ◽  
Amresh Kumar ◽  
Sabu Thomas ◽  
Subhash Chandra Mandal ◽  
...  

Background and Introduction: Sesquiterpene lactones are a class of secondary metabolite that contains sesquiterpenoids and lactone ring as pharmacophore moiety. A large group of bioactive secondary metabolites such as phytopharmaceuticals belong to this category. From the Asteraceae family-based medicinal plants, more than 5,000 sesquiterpene lactones have been reported so far. Sesquiterpene lactone-based pharmacophore moieties hold promise for broad-spectrum biological activities against cancer, inflammation, parasitic, bacterial, fungal, viral infection and other functional disorders. Moreover, these moiety based phytocompounds have been highlighted with a new dimension in the natural drug discovery program worldwide after the 2015 Medicine Nobel Prize achieved by the Artemisinin researchers. Objective: These bitter substances often contain an α, β-unsaturated-γ-lactone as a major structural backbone, which in recent studies has been explored to be associated with anti-tumor, cytotoxic, and anti-inflammatory action. Recently, the use of sesquiterpene lactones as phytomedicine has been increased. This study will review the prospect of sesquiterpene lactones against inflammation and cancer. Methods: Hence, we emphasized on the different features of this moiety by incorporating its structural diversity on biological activities to explore structure-activity relationships (SAR) against inflammation and cancer. Results: How the dual mode of action such as anti-inflammatory and anti-cancer has been exhibitedby these phytopharmaceuticals will be forecasted in this study. Furthermore, the correlation of anti-inflammatory and anti-cancer activity executed by the sesquiterpene lactones for fruitful phytotherapy will also be revealed in the present review in the milieu of pharmacophore activity relation and pharmacodynamics study as well. Conclusion: So, these metabolites are paramount in phytopharmacological aspects. The present discussion on the future prospect of this moiety based on the reported literature could be a guide for anti-inflammatory and anti-cancer drug discovery programs for the upcoming researchers.


2019 ◽  
Vol 19 (7) ◽  
pp. 842-874 ◽  
Author(s):  
Harbinder Singh ◽  
Nihar Kinarivala ◽  
Sahil Sharma

We live in a world with complex diseases such as cancer which cannot be cured with one-compound one-target based therapeutic paradigm. This could be due to the involvement of multiple pathogenic mechanisms. One-compound-various-targets stratagem has become a prevailing research topic in anti-cancer drug discovery. The simultaneous interruption of two or more targets has improved the therapeutic efficacy as compared to the specific targeted based therapy. In this review, six types of dual targeting agents along with some interesting strategies used for their design and synthesis are discussed. Their pharmacology with various types of the molecular interactions within their specific targets has also been described. This assemblage will reveal the recent trends and insights in front of the scientific community working in dual inhibitors and help them in designing the next generation of multi-targeted anti-cancer agents.


2016 ◽  
Vol 16 (10) ◽  
pp. 1339-1352 ◽  
Author(s):  
Alessandra C. Pinheiro ◽  
Thais C. Mendonça Nogueira ◽  
Marcus V.N. de Souza

2018 ◽  
Vol 11 (1) ◽  
pp. 015004 ◽  
Author(s):  
Wenfang Li ◽  
Xueyan Hu ◽  
Shuaitao Yang ◽  
Shuping Wang ◽  
Chenghong Zhang ◽  
...  

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