Design, Synthesis, and Antiproliferative and Apoptotic Assessment of Triazole-Tethered Bisnaphthalimide-Isatin Hybrids on Triple-Negative Breast and Prostate Cancers
Preeti, Asif Raza, Garima Arora, Amit Anand, Arun K. Sharma, Vipan Kumar
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引用次数: 0
Abstract
This study reports the design, synthesis, and biological evaluation of 1H-1,2,3-triazole-tethered bisnaphthalimide-isatin hybrids as potential antiproliferative agents. The compounds are efficiently synthesized via copper-promoted azide–alkyne cycloaddition and assayed against triple-negative breast (MDA-MB-231) and prostate (DU-145) cancer cell lines. Structure–activity relationship studies reveal that halogen substitution and spacer length substantially influenced anticancer activity. The bisnaphthalimide-isatin hybrid featuring dibromo substitution and a propyl linker demonstrates IC50 values of 3.3 ± 0.1 μM (DU-145) and 4.4 ± 0.3 μM (MDA-MB-231), comparable to clinical drugs cisplatin and 5-fluorouracil. Notably, it exhibits favorable selectivity indices (2.07–2.76) against cancer versus normal keratinocytes (HaCaT). Mechanistic investigations establish that it induces caspase-mediated apoptosis and molecular docking studies confirmed its strong interaction with DNA topoisomerase II (docking score: −4.894), comparable to doxorubicin.
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