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2000
Volume 25, Issue 20
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Objective

The present study aimed to design and synthesize a new series of benzothiazole analogues containing 1,3,4-thiadiazole, and assess their biological activities as potential anticancer agents.

Methods

N-(5,6-dimethylbenzo[]thiazol-2-yl)-2-((5-(substituted amino)-1,3,4-thiadiazol-2-yl)thio)acetamide derivatives () were synthesized the reaction of thiadiazole derivatives () with 2-chloro-N-(5,6-dimethylbenzo[]thiazol-2-yl)acetamide (1) in the presence of potassium carbonate. All the target compounds have been characterized by spectral analysis. The anticancer activities of compounds were tested against two human HT-1376 bladder and HT-29 colorectal carcinoma cells using the WST-1 assay. Flow cytometry was used for the determination of apoptosis, cell cycle, and caspase 3/7 activity. Moreover, wound-healing assay was utilized to evaluate cell migration. physicochemical, pharmacokinetics, and toxicological properties of compound were determined by pkCSM, SwissADME, and SwissTargetPrediction online web tools.

Results

Among all synthesized derivatives, compound (N-(5,6-dimethylbenzo[]thiazol-2-yl)-2-((5-((3-methoxyphenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide) recorded the highest antiproliferative activity against HT-1376 cells with an IC as 26.51 µM at 24 h, which was less cytotoxic than cisplatin (IC=14.85 µM). The combined treatment with compound and cisplatin increased the cellular apoptosis with a higher impact compared with the cisplatin group. The higher accumulation of cells in the G2 phase, a significant increase of caspase 3/7 activity, and the inhibition of migration rate were also observed in HT-1376 following a combination of compound and cisplatin treatment versus cisplatin alone, which might be involved in the apoptotic effects of compound .

Conclusion

The anticancer potential of compound lays the foundation for future research to focus on its value as a novel and advanced cancer therapy.

© 2025 Bentham Science Publishers
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2026-02-01

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Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Benzothiazole-Based 1,3,4-Thiadiazole Derivatives as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry 25, 1660 (2025); https://doi.org/10.2174/0118715206353584241018051852
/content/journals/acamc/10.2174/0118715206353584241018051852
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  • Article Type:     Research Article
Keyword(s): 1,3,4-thiadiazole; apoptosis; Benzothiazole; caspase 3/7; cell cycle arrest; cell migration

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