AUTHOR=Ye Jiahui , Mao Longfei , Xie Luoyijun , Zhang Rongjun , Liu Yulin , Peng Lizeng , Yang Jianxue , Li Qingjiao , Yuan Miaomiao 

TITLE=Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.753676

DOI=10.3389/fphar.2021.753676

ISSN=1663-9812

ABSTRACT=Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drug. Theophylline, a natural compound, is safe and easy to get and it can be used as a modified scaffold structure, hold huge potential for developing safe and efficient anti-tumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline-1,2,3-triazole compounds showed a good tumor suppressive efficacy. Especially, derivative d17 showed strong anti-proliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480 and PC-9. It is worth noting that the two NSCLC cell lines H460 and A549 are sensitive to compound d17 particularly, with IC50 of 5.929±0.97 μM and 6.76±0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis through increasing the ratio of apoptotic protein Bax/Bcl-2 by down-regulating the expression of phosphorylated Akt protein and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.