In Vitro and In Silico Evaluation of the Antitumor Potential of New Benzotriazole-1,2,4-Triazole Hybrids.
5 affiliations
- 1Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania.
- 2Research Center for Experimental Pharmacology and Drug Design (X-Pharm Design), "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania.
- 3Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania.
- 4Coriolan Dragulescu Institute of Chemistry, Romanian Academy, Bv. M. Viteazu, No. 24, 300223 Timisoara, Romania.
- 5Petru Poni Institute of Macromolecular Chemistry, 41A Aleea Gr. Ghica Vodă, 700487 Iaşi, Romania.
Abstract
Background/Objectives: One of the major problems facing the medical world is cancer, which causes millions of deaths each year. Nitrogen-containing heterocycles appear to offer a potential solution to this problem. Thus, the present study aimed to synthesize and characterize-both physicochemically and biologically-the new compounds obtained by combining benzotriazole and 1,2,4-triazole scaffolds. Methods: Each of the four cell lines (HaCaT-human keratinocyte, A375-melanoma, A549-non-small cell lung cancer, and HT-29-colorectal adenocarcinoma) was treated for 48 h with concentrations ranging from 10 to 100 µM of the four compounds. After 48 h of treatment, changes in cell viability were assessed using the Alamar Blue assay. These findings were supplemented by microscopic analysis of metabolic changes, as well as alterations in the actin cytoskeleton and nuclei, using staining techniques. Results: The results showed that MG-1 (p-chlorophenyl-) and MG-3 (p-(N,N-dimethylamino)phenyl-) are the most active compounds in our study, with IC₅₀ values for each tumor line as follows: 75.43 ± 2.77, 77.15 ± 1.32, and 96.28 ± 1.72 μM in A375, A549, and HT-29 cells, and 78.97 ± 3.08, 56.78 ± 2.57, and 69.19 ± 3.97 μM, respectively. In HaCaT cells, IC₅₀ values remained above 100 μM for all four hybrids. In silico screening identified MEK1 as the most favorable target for the investigated series, while 100 ns molecular dynamics simulations and MM-GBSA analysis supported stable binding of MG-1 and MG-3, with predicted binding free energies of -54.83 and -40.70 kcal/mol, respectively. Conclusions: Even with a limited set of compounds, we can conclude that the biological effect observed in our study depended on both the cell line and the substituent attached to the aryl moiety. The results obtained for MG-1 and MG-3 suggest that these compounds may serve as suitable starting points for further structural optimization and investigation of the mechanisms of action.
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BibTeX
@article{mardale2026vitro,
title = {{In Vitro and In Silico Evaluation of the Antitumor Potential of New Benzotriazole-1,2,4-Triazole Hybrids.}},
author = {Gabriel Mardale and Victor Dumitrașcu and Raluca Pop and Catalin Dumitru and Delia Muntean and Marius Mioc and Alexandra Mioc and Bogdan-Ionuț Mara and Mihaela Balan-Porcarasu and Oana Budu and Roxana Negrea-Ghiulai and Codruța Șoica},
journal = {Pharmaceuticals (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/ph19101591},
url = {https://europepmc.org/article/MED/42943288},
note = {CC BY},
}
RIS
TY - JOUR
TI - In Vitro and In Silico Evaluation of the Antitumor Potential of New Benzotriazole-1,2,4-Triazole Hybrids.
AU - Gabriel Mardale
AU - Victor Dumitrașcu
AU - Raluca Pop
AU - Catalin Dumitru
AU - Delia Muntean
AU - Marius Mioc
AU - Alexandra Mioc
AU - Bogdan-Ionuț Mara
AU - Mihaela Balan-Porcarasu
AU - Oana Budu
AU - Roxana Negrea-Ghiulai
AU - Codruța Șoica
PY - 2026
DA - 2026/10/08
JO - Pharmaceuticals (Basel, Switzerland)
DO - 10.3390/ph19101591
UR - https://europepmc.org/article/MED/42943288
AB - Background/Objectives: One of the major problems facing the medical world is cancer, which causes millions of deaths each year. Nitrogen-containing heterocycles appear to offer a potential solution to this problem. Thus, the present study aimed to synthesize and characterize-both physicochemically and biologically-the new compounds obtained by combining benzotriazole and 1,2,4-triazole scaffolds. Methods: Each of the four cell lines (HaCaT-human keratinocyte, A375-melanoma, A549-non-small cell lung cancer, and HT-29-colorectal adenocarcinoma) was treated for 48 h with concentrations ranging from 10 to 100 µM of the four compounds. After 48 h of treatment, changes in cell viability were assessed using the Alamar Blue assay. These findings were supplemented by microscopic analysis of metabolic changes, as well as alterations in the actin cytoskeleton and nuclei, using staining techniques. Results: The results showed that MG-1 (p-chlorophenyl-) and MG-3 (p-(N,N-dimethylamino)phenyl-) are the most active compounds in our study, with IC₅₀ values for each tumor line as follows: 75.43 ± 2.77, 77.15 ± 1.32, and 96.28 ± 1.72 μM in A375, A549, and HT-29 cells, and 78.97 ± 3.08, 56.78 ± 2.57, and 69.19 ± 3.97 μM, respectively. In HaCaT cells, IC₅₀ values remained above 100 μM for all four hybrids. In silico screening identified MEK1 as the most favorable target for the investigated series, while 100 ns molecular dynamics simulations and MM-GBSA analysis supported stable binding of MG-1 and MG-3, with predicted binding free energies of -54.83 and -40.70 kcal/mol, respectively. Conclusions: Even with a limited set of compounds, we can conclude that the biological effect observed in our study depended on both the cell line and the substituent attached to the aryl moiety. The results obtained for MG-1 and MG-3 suggest that these compounds may serve as suitable starting points for further structural optimization and investigation of the mechanisms of action.
SN - 1424-8247
ER -