Design, Synthesis, and Molecular Docking Studies of Indolo[3,2-c]Quinolines as Topoisomerase Inhibitors


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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 in vitro 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 IC50 values were less than 0.9 μM. On the other hand, cisplatin revealed an IC50 value of 2.36 μM. Moreover, they exhibited inhibitory activity against both Topoisomerase (Topo) I and II. The most potent compound, 5g, demonstrated a suppressive impact on topoisomerase I, with an IC50 value of 2.9 μM compared to the positive control Camptothecin (IC50 1.64 μM) and compound 8 displayed remarkable topoisomerase II inhibitory activity with an IC50 of 6.82 μM compared to the positive control Doxorubicin (IC50 6.49 μM). The cell cycle study for compounds 5g and 8 revealed that cell cycle arrest occurred at the G1/S and S phases, respectively. Compounds 5g and 8 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 5g and 8 can be considered promising candidates for further anti-cancer drug development, which might be related to inhibiting TOPO I and TOPO II activities.

作者简介

Mohamed Badr

Department of Biochemistry, Faculty of Pharmacy, Menoufia University

Email: info@benthamscience.net

Elshaymaa Elmongy

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University

编辑信件的主要联系方式.
Email: info@benthamscience.net

Ibrahim Sayed

Chemistry Department, Faculty of Science,, Menoufia University

编辑信件的主要联系方式.
Email: info@benthamscience.net

Yasmine Moemen

Clinical Pathology Department, National Liver Institute, Menoufia University

Email: info@benthamscience.net

Ashraf Khalil

Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University

Email: info@benthamscience.net

Doaa Elkhateeb

Chemistry Department, Faculty of Science,, Menoufia University

Email: info@benthamscience.net

Reem Binsuwaidan

Department of Pharmaceutical Sciences, College of Pharmacy,, Princess Nourah bint Abdulrahman University,

Email: info@benthamscience.net

Hadeer Ali

Chemistry Department, Faculty of Science,, Menoufia University

Email: info@benthamscience.net

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