Quinoxaline–Triazole Hybrids: Exploring the Impact of Substituent Architecture on Cytotoxic Potency and Receptor Interaction

ABSTRACT A series of quinoxaline–1,2,4‐triazole derivatives ( 6a – 6l ) was synthesized and characterized by NMR and mass spectrometry; yields reached 80% for the long‐chain alkyl members, which points to substituent architecture as the determining factor in synthetic efficiency. MTT assays against MCF‐7, HeLa, and HepG2 cells identified 6e and 6k as the most active compounds, with IC 50 values of 50.83–62.69 µg/mL across the three lines. Docking against the adenosine A1 receptor gave binding energies of −9.02 kcal/mol for 6e and −9.24 kcal/mol for 6k , driven by hydrophobic and π–π interactions with key binding‐site residues. Ligand–receptor complexes remained stable through 600 ns of molecular dynamics, and umbrella sampling estimated binding free energies of −129.46 and −88.46 kJ/mol, respectively. ADMET predictions indicated drug‐likeness and favorable gastrointestinal absorption. 6e and 6k are therefore taken forward as lead candidates for mechanistic, pharmacological and in vivo evaluation.

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Publication Details

Journal
Chemistry & Biodiversity
Published
2026-10-30
DOI
https://doi.org/10.1002/cbdv.71770
Primary Topic
Synthesis and Biological Evaluation
Type
article
Field-Weighted Citation Impact
0.00

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article

Quinoxaline–Triazole Hybrids: Exploring the Impact of Substituent Architecture on Cytotoxic Potency and Receptor Interaction

Jamoliddin Razzokov, Kamala Prasad Vasikarla, Mukhriddin Makhkamov, Peddiahgari Vasu Govardhana Reddy et al.
3 links
Chemistry & Biodiversity
Synthesis and Biological Evaluation
article

Quinoxaline–Triazole Hybrids: Exploring the Impact of Substituent Architecture on Cytotoxic Potency and Receptor Interaction

Jamoliddin Razzokov, Kamala Prasad Vasikarla, Mukhriddin Makhkamov, Peddiahgari Vasu Govardhana Reddy, Parthiban Marimuthu, Aminul Islam, Shaik Farheen Banu, Mandapalli Sreeshitha, Bangar Reddy Vancha, Satyanarayana Swamy Vyshnava
article en

Abstract

ABSTRACT A series of quinoxaline–1,2,4‐triazole derivatives ( 6a – 6l ) was synthesized and characterized by NMR and mass spectrometry; yields reached 80% for the long‐chain alkyl members, which points to substituent architecture as the determining factor in synthetic efficiency. MTT assays against MCF‐7, HeLa, and HepG2 cells identified 6e and 6k as the most active compounds, with IC 50 values of 50.83–62.69 µg/mL across the three lines. Docking against the adenosine A1 receptor gave binding energies of −9.02 kcal/mol for 6e and −9.24 kcal/mol for 6k , driven by hydrophobic and π–π interactions with key binding‐site residues. Ligand–receptor complexes remained stable through 600 ns of molecular dynamics, and umbrella sampling estimated binding free energies of −129.46 and −88.46 kJ/mol, respectively. ADMET predictions indicated drug‐likeness and favorable gastrointestinal absorption. 6e and 6k are therefore taken forward as lead candidates for mechanistic, pharmacological and in vivo evaluation.

Chemistry & BiodiversityVol. 23(11)
Åbo Akademi University (FI), Academy of Sciences Republic of Uzbekistan (UZ), Tashkent State Technical University named after Islam Karimov (UZ), Tashkent Institute of Irrigation and Agricultural Mechanization Engineers (UZ), Malla Reddy University (IN), Yogi Vemana University (IN)
Arthritis National Research Foundation, National Research Foundation, China Scholarship Council, Åbo Akademi, Biocenter Finland
Good health and well-being
Openalex Percentile: Top 26%
Synthesis and Biological Evaluation
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