Novel Triazolopyridine Derivatives: Synthesis, Antimicrobial, Anticancer Evaluation and Molecular Docking Studies

ABSTRACT This study investigated the design, synthesis, screening, and functionalization of a novel compound,1,6‐diamino‐4‐(3,5‐dimethoxyphenyl)‐2‐oxo‐1,2‐dihydropyridine‐3,5dicarbonitrile ( 4 ), utilizing active carbonyl compounds, acetic acid, and aldehydes to generate new triazolopyridine derivatives. The molecular structures of these derivatives were elucidated through various spectroscopic methods and elemental analysis, including FT‐IR, 1 H NMR, 13 C NMR, and mass spectrometry. Antimicrobial evaluation by the disc diffusion method was conducted against several microorganisms such as Salmonella typhimurium , Candida albicans , Pseudomonas aeruginosa , Bacillus subtilis , and others, with compounds 4, 5, 6, and 10 exhibiting the most significant antimicrobial activity. Furthermore, compounds 4‐10 were assessed for them in vitro cytotoxic effects on HepG‐2, MDA‐MB‐231, HCT‐116, and MCF‐7 human cancer cell lines, as well as the BJ‐1 human healthy cell line, using doxorubicin as a reference drug. All tested compounds demonstrated high activity against the hormone‐dependent human breast cancer cell line (MCF‐7) and may serve as promising candidates for this cancer type. Notably, compounds 4 and 6 exhibited selective activity against the hormone‐dependent human breast cancer (MCF‐7), human colon cancer (HCT‐116), and human liver cancer (HepG2) cell lines, while remaining inactive against the hormone‐independent breast cancer cell line (MDA‐MB‐231).