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Vol. 37 No. 12 (2025): Vol 37 Issue 12, 2025

Copyright (c) 2025 Nitin Kumar kumar, Neetika lal, Vishal Nemaysh, Pratibha Mehta Luthra

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Design, Synthesis, in vitro Anticancer Activity, Topoisomerase-I Inhibition and DNA Binding Studies of Substituted Carbazole Semicarbazone Derivatives

https://doi.org/10.14233/ajchem.2025.34341
Nitin Kumar
Neuropharmaceutical Chemistry Research Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi-110007, India
Neetika Lal
Neuropharmaceutical Chemistry Research Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi-110007, India
Vishal Nemaysh
Neuropharmaceutical Chemistry Research Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi-110007, India
https://orcid.org/0000-0002-6612-8096
Pratibha Mehta Luthra
Neuropharmaceutical Chemistry Research Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi-110007, India
https://orcid.org/0000-0002-4164-6508

Corresponding Author(s) : Nitin Kumar

nitinvishnoi@gmail.com

Asian Journal of Chemistry, Vol. 37 No. 12 (2025): Vol 37 Issue 12, 2025

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and deadly form of brain tumor in adults. In the search for more effective anticancer agents, tricyclic compounds such as carbazole derivatives have garnered considerable attention. This study aims to design and synthesize new substituted carbazole semicarbazone derivatives and evaluate their in vitro anticancer profile (IC50) on U87 MG glioma cell line based on MTT assay and DNA binding mechanism of one potent cytotoxic compound with calf thymus DNA via spectroscopic methods, topoisomerase assay and in silico approach. Reaction of 6-substituted carbazole-3-carbaldehyde with semicarbazide in 1:1 ratio reflux in ethanol gave 6-substituted carbazole semicarbazone derivatives and their structure elucidated by their melting point, NMR, FT-IR, HRMS spectroscopy. DNA binding studies of one potent cytotoxic carbazole derivative with ct-DNA (calf-thymus) in physiological buffer (pH 7.4) carried via various spectroscopic techniques like electronic absorption, circular dichroism (CD), viscosity test, topoisomerase assay and computational method. Two carbazole semicarbazone derivatives [(6-bromo-1,4-dimethyl-9H-carbazol-3-yl)-methylideneamino]urea (21) and [(6-methoxy-1,4-dimethyl-9H-carbazol-3-yl)methylideneamino]urea (22) found the best anticancer activities against the U87MG glioma cell line with the 50% inhibitory concentration (IC50) values IC50 = 23.3 ± 4 µM and 13.82 ± 3.86 µM, respectively also which even better than standard drug temozolomide (IC50 = 100 µM). Spectroscopic studies (UV absorption, circular dichroism), viscosity test and molecular docking analysis confirmed that carbazole semicarbazone (22) has groove binding mode with ct-DNA. Only topoisomerase assay, compound 22 showed groove binding mode interaction concentration dependent manner. These carbazole semicarbazone derivatives demonstrated potent anticancer activity against the U87MG glioma cell line. Spectroscopic analyses, viscosity test and molecular docking confirmed that compound 22 interacts with ct-DNA via a groove binding mode. Moreover, topoisomerase inhibition assays supported this interaction in a concentration-dependent manner, suggesting that compound 22 may exert its anticancer effect through DNA-targeted mechanisms.

Keywords

Glioblastoma Carbazoles Semicarbazone Topoisomerase enzyme
(1)
Kumar, N.; Lal, N.; Nemaysh, V.; Luthra, P. M. Design, Synthesis, in Vitro Anticancer Activity, Topoisomerase-I Inhibition and DNA Binding Studies of Substituted Carbazole Semicarbazone Derivatives. ajc 2025, 37, 3136-3146.
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