Synthesis and In Silico and In Vitro Antitumor Potential of Novel Organochalcogens Derived from Azidothymidine and 2,4,6-Trichloro-1,3,5-triazine
4 affiliations
- 1Federal University of Santa Maria - Universidade Federal de Santa Maria , , Av. Roraima, 1000 , , ,
- 2Federal University of Santa Maria , , Av. Roraima, 1000 , , ,
- 3Federal University of Santa Maria , , Santa Maria, Av. Roraima, 1000 , , ,
- 4Federal University of Rio Grande do Sul , , Av. Bento Gonçalves, 9500 , , ,
Abstract
The preparation of a new class of organochalcogen compounds derived from arylchalcogeno aminothymidine (ACAT) and 2,4,6-trichloro-1,3,5-triazine is described. The compounds were obtained in good yields via aromatic nucleophilic substitution reactions between ACAT derivatives and the triazine ring. The developed protocol selectively afforded monosubstituted derivatives, avoiding the formation of di- and trisubstituted isomers. Antitumor activity was evaluated against HT-29 (human colorectal adenocarcinoma) and NCI/ADR-RES (multidrug-resistant human ovarian carcinoma) cell lines using the MTT assay. Sulfur- and selenium-containing derivatives showed only moderate cytotoxic effects, reducing cell viability mainly at the highest tested concentration (100 μM). In contrast, tellurium-containing derivatives exhibited pronounced cytotoxic activity, with minimum IC50 values of 9.90 μM in HT-29 cells and 12.18 μM in NCI/ADR-RES cells, demonstrating notable efficacy against multidrug-resistant tumor cells. In addition, the antioxidant properties of the compounds were investigated in vitro. Tellurium derivatives displayed significant antioxidant activity, as demonstrated by inhibition of lipid peroxidation in the TBARS assay and by thiol-peroxidase (GPx-like) activity. A possible mechanism of action based on tubulin polymerization inhibition was investigated by means of a molecular docking study. The results demonstrate the potential of these novel organochalcogen compounds as antitumor agents, highlighting tellurium incorporation as a promising strategy to overcome multiple drug resistance (MDR) in cancer.
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BibTeX
@article{rocha2026synthesis,
title = {{Synthesis and In Silico and In Vitro Antitumor Potential of Novel Organochalcogens Derived from Azidothymidine and 2,4,6-Trichloro-1,3,5-triazine}},
author = {Nayra Salazar Rocha and Sidne Rodrigues da Silva and Brenda Bomm Carvalho and Marcelo Wendt and Luciano Dornelles and Luciana Filippin Cossetin and Bianca Costa Maia-do-Amaral and Daniele Rubert Nogueira-Librelotto and Raquel Mello da Rosa and Alessandro de Souza Prestes and João Cândido Pilar Mayer and Nilda Vargas Barbosa and João Batista Teixeira da Rocha and Oscar Endrigo Dorneles Rodrigues},
journal = {ACS Omega},
year = {2026},
month = oct,
doi = {10.1021/acsomega.6c07643},
url = {https://pubs.acs.org/acsodf/article/11/42/65276/5448480/Synthesis-and-In-Silico-and-In-Vitro-Antitumor},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Synthesis and In Silico and In Vitro Antitumor Potential of Novel Organochalcogens Derived from Azidothymidine and 2,4,6-Trichloro-1,3,5-triazine
AU - Nayra Salazar Rocha
AU - Sidne Rodrigues da Silva
AU - Brenda Bomm Carvalho
AU - Marcelo Wendt
AU - Luciano Dornelles
AU - Luciana Filippin Cossetin
AU - Bianca Costa Maia-do-Amaral
AU - Daniele Rubert Nogueira-Librelotto
AU - Raquel Mello da Rosa
AU - Alessandro de Souza Prestes
AU - João Cândido Pilar Mayer
AU - Nilda Vargas Barbosa
AU - João Batista Teixeira da Rocha
AU - Oscar Endrigo Dorneles Rodrigues
PY - 2026
DA - 2026/10/10
JO - ACS Omega
DO - 10.1021/acsomega.6c07643
UR - https://pubs.acs.org/acsodf/article/11/42/65276/5448480/Synthesis-and-In-Silico-and-In-Vitro-Antitumor
AB - The preparation of a new class of organochalcogen compounds derived from arylchalcogeno aminothymidine (ACAT) and 2,4,6-trichloro-1,3,5-triazine is described. The compounds were obtained in good yields via aromatic nucleophilic substitution reactions between ACAT derivatives and the triazine ring. The developed protocol selectively afforded monosubstituted derivatives, avoiding the formation of di- and trisubstituted isomers. Antitumor activity was evaluated against HT-29 (human colorectal adenocarcinoma) and NCI/ADR-RES (multidrug-resistant human ovarian carcinoma) cell lines using the MTT assay. Sulfur- and selenium-containing derivatives showed only moderate cytotoxic effects, reducing cell viability mainly at the highest tested concentration (100 μM). In contrast, tellurium-containing derivatives exhibited pronounced cytotoxic activity, with minimum IC50 values of 9.90 μM in HT-29 cells and 12.18 μM in NCI/ADR-RES cells, demonstrating notable efficacy against multidrug-resistant tumor cells. In addition, the antioxidant properties of the compounds were investigated in vitro. Tellurium derivatives displayed significant antioxidant activity, as demonstrated by inhibition of lipid peroxidation in the TBARS assay and by thiol-peroxidase (GPx-like) activity. A possible mechanism of action based on tubulin polymerization inhibition was investigated by means of a molecular docking study. The results demonstrate the potential of these novel organochalcogen compounds as antitumor agents, highlighting tellurium incorporation as a promising strategy to overcome multiple drug resistance (MDR) in cancer.
SN - 2470-1343
ER -