Design, Synthesis and Biological Evaluation of Biphenyl-1,2,3-Triazole Hybrid Analogues as PD-1/PD-L1 Inhibitors

Research Article | International Journal of Pharmacology
Design, Synthesis and Biological Evaluation of Biphenyl-1,2,3-Triazole Hybrid Analogues as PD-1/PD-L1 Inhibitors
Author's Information

Shijia Zhou

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Suresh Narva

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Mengda Wu

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Ming Wang

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Feng Zhang

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Chenfeng Shen

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Annoor Awadasseid

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Wen Zhang

Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
Abstract

Background and Objective: Inhibition of PD-1/PD-L1 with small molecules has shown promise as a potential therapy for certain cancers. This study aimed to synthesize and evaluate the antineoplastic activity of thirty biphenyl-1,2,3-triazole hybrid analogues. Materials and Methods: The effectiveness of inhibitors against PD-1/PD-L1 binding was evaluated using Homogeneous Time-Resolved Fluorescence (HTRF), the CCK-8 assay to assess the ability of the compounds to inhibit tumor cell proliferation and the wound-healing assay to study cell migration and cell-cell interaction. Results: Current findings indicated that compounds 6d, 6e and 6h exhibit strong anti-proliferative activity against A549, MDA-MB-231 and HCC827 cancer cells via the non-immune pathway. Specifically, they displayed potent inhibitory effects against A549 cells, with IC₅₀ values of 0.315±0.13, 0.821±0.07 and 0.576±0.15 μM, respectively, suggesting that they have potential as anti-lung cancer drugs. Despite their potent anti-tumor activity, our compounds showed only weak inhibition of the PD-1/PD-L1 interaction, as evaluated by HTRF analysis. Conclusion: Results of the present study indicated that compounds 6d, 6e and 6h have anticancer efficacy through both immunological and non-immune mechanisms, specifically by inhibiting the PD-1/PD-L1 combination.

Keywords

anti-cancer activity,biphenyl-1,2,3-triazole hybrid analogues,small molecule inhibitors,Synthesis

DOI: 10.3923/ijp.2024.106.114

ADLID: 81757-v8

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Keywords
anti-cancer activity biphenyl-1 2 3-triazole hybrid analogues small molecule inhibitors Synthesis

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