# Design, synthesis, structural characterization, anticancer evaluation, and computational studies of novel quinoline-1,2,3-triazole glycohybrids

## TL;DR

Scientists designed and tested new quinoline-triazole compounds with sugar parts, finding some showed weak cancer cell toxicity and good binding to a breast cancer receptor.

## Contribution

The paper introduces novel quinoline-1,2,3-triazole glycohybrids with structural and computational analysis for anticancer activity.

## Key findings

- Most compounds showed no significant anticancer activity, but three had weak cytotoxic effects (IC50 108.59–135.95 µM).
- Molecular docking showed good binding affinities to estrogen receptor alpha (up to −9.1 kcal mol−1).
- DFT calculations provided insights into electronic properties like HOMO–LUMO energies and reactivity.

## Abstract

A novel series of eleven phenyl-substituted quinoline 1,2,3-triazole glycoconjugates 6(a–k) was synthesized via the copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between 2-phenyl-substituted quinoline-4-carboxylic acid propargyl ester (4a–4e) and various sugar azides (5a, 5b, and 5c). The obtained compounds were comprehensively characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The chemical structures of compounds 6a, 6b, and 6e were further established by single-crystal X-ray diffraction analysis. Their crystal packing was stabilized through a network of intermolecular hydrogen bonds involving C–H⋯N, N–H⋯N, and C–H⋯O (sp2, sp3) interactions, which were qualitatively analyzed using Hirshfeld surface analysis. In vitro anticancer evaluation against the MCF-7 breast cancer cell line revealed that most of the compounds of the series were inactive, while compounds 6c, 6d, and 6f exhibited only weakly cytotoxic activity (IC50 values of 108.59–135.95 µM). Molecular docking with estrogen receptor alpha (ERα, PDB ID: 3ERT) revealed good binding affinities (up to −9.1 kcal mol−1), comparable to the reference ligand (−9.7 kcal mol−1). Furthermore, DFT calculations were performed to evaluate key electronic parameters (HOMO–LUMO energies, reactivity, stability, and charge distribution), offering insight into the compounds' chemical behaviour and electronic properties.

Phenyl-substituted quinoline–1,2,3-triazole glycoconjugates were synthesized via CuAAC and characterized by spectroscopy and X-ray analysis. Crystal packing, molecular docking, and DFT studies elucidated structural and electronic features.