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Volume 25, Issue 14
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

The tetracyclic indoloquinoline ring system has attracted considerable interest in the recent past due to its broad spectrum of biological activities and its binding to various types of nucleic acids.

Objective

This study aims to elucidate their interactions with DNA and their effects on topoisomerases (TOPO) I and II.

Methods

Several compounds derived from 6-amino-11H-indolo[3,2-c]quinoline with diverse groups on the quinoline ring have been successfully synthesized according to a previously established protocol where all the synthesized indolo[3,2-c]quinoline derivatives were evaluated against A549, HCT-116, BALB/3T3, and MV4-11 cell lines using MTT (3-[4,5- dimethylthiazol-2-yl]-2,5-diphenyl- tetrazolium bromide) assay. These derivatives were then screened for their topo I and II inhibitory activities.

Results

The tested compounds were more effective at killing MV4-11 leukemia cells than the standard cancer drug cisplatin, as shown by the fact that their IC values were less than 0.9 μM. On the other hand, cisplatin revealed an IC value of 2.36 μM. Moreover, they exhibited inhibitory activity against both Topoisomerase (Topo) I and II. The most potent compound, , demonstrated a suppressive impact on topoisomerase I, with an IC value of 2.9 μM compared to the positive control Camptothecin (IC 1.64 μM) and compound displayed remarkable topoisomerase II inhibitory activity with an IC of 6.82 μM compared to the positive control Doxorubicin (IC 6.49 μM). The cell cycle study for compounds and revealed that cell cycle arrest occurred at the G1/S and S phases, respectively. Compounds and showed a high selectivity index, which suggests that they could be used to develop low-toxicity chemotherapeutic agents.

Conclusion

The results of this study demonstrate that compounds and can be considered promising candidates for further anti-cancer drug development, which might be related to inhibiting TOPO I and TOPO II activities.

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2025-02-03
2025-07-12

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/content/journals/acamc/10.2174/0118715206360700241219065917
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Design, Synthesis, and Molecular Docking Studies of Indolo[3,2-c]Quinolines as Topoisomerase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 1029 (2025); https://doi.org/10.2174/0118715206360700241219065917
/content/journals/acamc/10.2174/0118715206360700241219065917
/content/journals/acamc/10.2174/0118715206360700241219065917
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  • Article Type:     Research Article
Keyword(s): anticancer agents; apoptosis; Indoloquinoline; molecular docking; MV4-11 leukemia cells; topoisomerase inhibitors

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