Quinoxaline-Triazole Hybrids: Exploring the Impact of Substituent Architecture on Cytotoxic Potency and Receptor Interaction.
9 affiliations
- 1Department of Chemistry, Yogi Vemana University, Kadapa, Andhra Pradesh, India.
- 2Coromandel Innovation Centre, Coromandel International Limited, Hyderabad, Telangana, India.
- 3Research and Development Department, Denisco Chemicals Pvt Ltd, Hyderabad, Telangana, India.
- 4Department of BMB, School of Allied Healthcare Sciences, Malla Reddy University, Hyderabad, Telangana, India.
- 5Institute of Bioorganic Chemistry of Uzbekistan Academy of Sciences, Tashkent, Uzbekistan.
- 6Laboratory of Experimental Biophysics, Centre for Advanced Technologies, Tashkent, Uzbekistan.
- 7Pharmaceutical Sciences Laboratory, Faculty of Pharmacy, Åbo Akademi University, Turku, Finland.
- 8Institute of Fundamental and Applied Research, National Research University TIIAME, Tashkent, Uzbekistan.
- 9Department of Biotechnology, Tashkent State Technical University, Tashkent, Uzbekistan.
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 IC₅₀ 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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BibTeX
@article{vancha2026quinoxalinetriazole,
title = {{Quinoxaline-Triazole Hybrids: Exploring the Impact of Substituent Architecture on Cytotoxic Potency and Receptor Interaction.}},
author = {Bangar Reddy Vancha and Mandapalli Sreeshitha and Shaik Farheen Banu and Kamala Prasad Vasikarla and Satyanarayana Swamy Vyshnava and Mukhriddin Makhkamov and Parthiban Marimuthu and Jamoliddin Razzokov and Aminul Islam and Peddiahgari Vasu Govardhana Reddy},
journal = {Chemistry \& biodiversity},
year = {2026},
month = oct,
doi = {10.1002/cbdv.71770},
url = {https://europepmc.org/article/MED/42960685},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Quinoxaline-Triazole Hybrids: Exploring the Impact of Substituent Architecture on Cytotoxic Potency and Receptor Interaction.
AU - Bangar Reddy Vancha
AU - Mandapalli Sreeshitha
AU - Shaik Farheen Banu
AU - Kamala Prasad Vasikarla
AU - Satyanarayana Swamy Vyshnava
AU - Mukhriddin Makhkamov
AU - Parthiban Marimuthu
AU - Jamoliddin Razzokov
AU - Aminul Islam
AU - Peddiahgari Vasu Govardhana Reddy
PY - 2026
DA - 2026/10/30
JO - Chemistry & biodiversity
DO - 10.1002/cbdv.71770
UR - https://europepmc.org/article/MED/42960685
AB - 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 IC₅₀ 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.
SN - 1612-1872
SN - 1612-1880
ER -