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Synthesis, X-ray crystal structure, anticancer activity, DFT, and molecular docking studies of 1,2,4-triazole linked indolyl thioglycosides.

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Title: Synthesis, X-ray crystal structure, anticancer activity, DFT, and molecular docking studies of 1,2,4-triazole linked indolyl thioglycosides.
Authors: Chauhan, Deepanshi1 (AUTHOR), Kumar, Ravendra1 (AUTHOR), Gupta, Rakesh Kumar2 (AUTHOR), Pratap, Rajesh3 (AUTHOR), Dubey, Pawan K.2 (AUTHOR), Kushwaha, Divya1 (AUTHOR) divyakush.mmvbhu@ac.in
Source: Journal of Molecular Structure. Feb2026:Part 2, Vol. 1351, pN.PAG-N.PAG. 1p.
Subjects: X-ray crystallography, Antineoplastic agents, Molecular docking, Triazole derivatives, Density functional theory, Chemical synthesis
Abstract: • Efficient synthesis and structural characterization of 1,2,4-triazole-linked indole thioglycosides (9a – c). • X-ray crystallographic analysis revealed complex intermolecular (sp³/sp²) C–H...π interactions and hydrogen-bonding networks involving (sp³/sp²) C–H...N/O and N–H...N contacts. • DFT studies (HOMO–LUMO, MEP, NBO, and dual descriptor analyses) provided insights into electronic structure, chemical reactivity, and possible drug–receptor interactions. • Anticancer potential against MCF-7 breast cancer cells, further supported by molecular docking and ADMET predictions. In this study, a series of 1,2,4-triazole-linked indole thioglycosides (9a – c) was synthesized via nucleophilic substitution of 5-(1 H -indol-2-yl)-4-phenyl-2,4-dihydro-3 H -1,2,4-triazole-3-thione (5) with glycosyl bromides (8a – c). The structure of the compounds was elucidated using spectroscopic techniques, including NMR, IR, and HRMS. The molecular structures of compounds 9a and 9b were further confirmed by single-crystal X-ray diffraction. The configurations of the glycosidic and heterocyclic moieties were examined through analysis of the planarity of key structural fragments and the dihedral angles between them. The anticancer potential of the compounds was evaluated in vitro against the MCF-7 human breast cancer cell line, where compounds demonstrated moderate to poor cytotoxic activity. Molecular docking studies revealed strong binding affinities of the synthesized compounds toward the CDK2 enzyme (−9.1 to −9.2 kcal/mol), comparable to that of the reference inhibitor roscovitine. Additionally, DFT calculations were performed to evaluate key electronic and chemical parameters such as HOMO–LUMO energies, reactivity, stability, electronegativity, chemical potential, electrophilicity, and electronic charge distribution. These insights provide a deeper understanding of the compounds' chemical behaviour and can aid in predicting their reactivity and interactions, particularly in the context of drug–receptor binding. [Display omitted] [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
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Abstract:• Efficient synthesis and structural characterization of 1,2,4-triazole-linked indole thioglycosides (9a – c). • X-ray crystallographic analysis revealed complex intermolecular (sp³/sp²) C–H...π interactions and hydrogen-bonding networks involving (sp³/sp²) C–H...N/O and N–H...N contacts. • DFT studies (HOMO–LUMO, MEP, NBO, and dual descriptor analyses) provided insights into electronic structure, chemical reactivity, and possible drug–receptor interactions. • Anticancer potential against MCF-7 breast cancer cells, further supported by molecular docking and ADMET predictions. In this study, a series of 1,2,4-triazole-linked indole thioglycosides (9a – c) was synthesized via nucleophilic substitution of 5-(1 H -indol-2-yl)-4-phenyl-2,4-dihydro-3 H -1,2,4-triazole-3-thione (5) with glycosyl bromides (8a – c). The structure of the compounds was elucidated using spectroscopic techniques, including NMR, IR, and HRMS. The molecular structures of compounds 9a and 9b were further confirmed by single-crystal X-ray diffraction. The configurations of the glycosidic and heterocyclic moieties were examined through analysis of the planarity of key structural fragments and the dihedral angles between them. The anticancer potential of the compounds was evaluated in vitro against the MCF-7 human breast cancer cell line, where compounds demonstrated moderate to poor cytotoxic activity. Molecular docking studies revealed strong binding affinities of the synthesized compounds toward the CDK2 enzyme (−9.1 to −9.2 kcal/mol), comparable to that of the reference inhibitor roscovitine. Additionally, DFT calculations were performed to evaluate key electronic and chemical parameters such as HOMO–LUMO energies, reactivity, stability, electronegativity, chemical potential, electrophilicity, and electronic charge distribution. These insights provide a deeper understanding of the compounds' chemical behaviour and can aid in predicting their reactivity and interactions, particularly in the context of drug–receptor binding. [Display omitted] [ABSTRACT FROM AUTHOR]
ISSN:00222860
DOI:10.1016/j.molstruc.2025.144243