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2000
Volume 26, Issue 3
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Introduction

Heterocyclic compounds serve as the structural framework for many commercially available drugs and are well known for their antitumor properties.

Aim

This study aimed to evaluate the cytotoxic effects, apoptosis induction, changes in cell cycle progression, and gene expression alterations of new heterocyclic compounds and their precursors against the acute monocytic leukemia cell line THP-1 through experimentation and computational approaches.

Methods

The study employed cytotoxicity assays, flow cytometry analyses, gene expression evaluations, oral bioavailability studies, and molecular modeling. Among the compounds tested, , , and demonstrated the greatest potency and selectivity, exhibiting substantially increased cytotoxicity (1.18 μM < < 7.66 μM) against the THP-1 cell line. Investigations into apoptosis induction and cell cycle changes revealed that these compounds primarily caused an increase in the number of THP-1 cells undergoing apoptosis after 48 hours of treatment. Additionally, compounds and induced an accumulation of cells in the G0/G1 phase in the same cell line.

Results

Regarding gene expression, a shift in the expression profile of genes associated with apoptotic mechanisms was observed. Furthermore, analysis revealed that these three active compounds potentially interact with histone deacetylase 8 (HDAC8), a protein known to be associated with cancer.

Conclusion

These findings underscore the potential of these compounds as candidates for the development of novel therapeutic approaches in oncology.

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/content/journals/acamc/10.2174/0118715206370289250313062830
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Novel Heterocyclic Compounds Exhibit Potent Antileukemic Activity through Selective Induction of Apoptosis and HDAC8 Interaction in AML Cells
Anti-Cancer Agents in Medicinal Chemistry 26, 289 (2026); https://doi.org/10.2174/0118715206370289250313062830
/content/journals/acamc/10.2174/0118715206370289250313062830
/content/journals/acamc/10.2174/0118715206370289250313062830
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  • Article Type:     Research Article
Keyword(s): acute monocytic leukemia; apoptosis; cell cycle arrest; hematologic malignancy; Heterocyclic compounds; histone deacetylase 8 (HDAC8)

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