1,2,3-Triazole-Containing Compounds as Anti-Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure-Activity Relationship.

Ting Liang,Guihua Hou,Xiangyang Sun,Feng Gao,Wenhong Li

doi:10.3389/fphar.2021.661173

Abstract

Lung cancer is the most common malignancy and leads to around one-quarter of all cancer deaths. Great advances have been achieved in the treatment of lung cancer with novel anticancer agents and improved technology. However, morbidity and mortality rates remain extremely high, calling for an urgent need to develop novel anti–lung cancer agents. 1,2,3-Triazole could be readily interact with diverse enzymes and receptors in organisms through weak interaction. 1,2,3-Triazole can not only be acted as a linker to tether different pharmacophores but also serve as a pharmacophore. This review aims to summarize the recent advances in 1,2,3-triazole–containing compounds with anti–lung cancer potential, and their structure–activity relationship (SAR) together with mechanisms of action is also discussed to pave the way for the further rational development of novel anti–lung cancer candidates.

Highlights

Lung cancer has high morbidity and represents the leading cause of cancer-related deaths (Nasim et al, 2019; Willis et al, 2019; Bade and Dela Cruz, 2020; Majem et al, 2020; Salehi et al, 2020; Zhang et al, 2020)
This review summarizes the current developments, mechanisms of action, and structure–activity relationships (SARs) of 1,2,3-triazole–containing compounds with anti–lung cancer potential to pave the way for further rational development
As a cancer with the highest morbidity, is the leading cause of cancer-related deaths and has already posed heavy burden on the world health system, which makes an urgent need to develop novel anti–lung cancer agents. 1,2,3-Triazole could readily interact with diverse enzymes and receptors in organisms through weak interaction and has been considered as a privileged structure in medicinal chemistry. 1,2,3-Triazole–containing agent CAI synergizes with sorafenib to combat NSCLC through the inhibition of NANOG and aggravation of apoptosis, indicating that 1,2,3-triazole–containing derivatives are useful scaffolds to develop novel anti–lung cancer agents

Summary

Introduction

Lung cancer has high morbidity and represents the leading cause of cancer-related deaths (around 20% of all mortalities in cancer) (Nasim et al, 2019; Willis et al, 2019; Bade and Dela Cruz, 2020; Majem et al, 2020; Salehi et al, 2020; Zhang et al, 2020). With the development of novel anticancer agents and improvement of technology, lung cancer treatment has achieved great progress in recent decades, but the morbidity and mortality rates remain high and the overall 5-year survival rate is only around 15% (Gray et al, 2019; Coakley and Popat, 2020). The 1,2,3triazole–containing agent carboxyamidotriazole (CAI) could synergise with sorafenib to combat NSCLC by inhibiting NANOG and aggravating apoptosis (Ferreira et al, 2013; Chen et al, 2017). These studies suggest that 1,2,3-triazole derivatives are useful scaffolds for development of novel anti–lung cancer agents with low toxicity and high efficacy

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Conclusion