Luo, S.-Y.; Zeng, C.-M.; Xu, P.; Ning, Y.; Dong, M.-L.; Zhang, W.-H.; Yu, G. Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability. Preprints2024, 2024071597. https://doi.org/10.20944/preprints202407.1597.v1
APA Style
Luo, S. Y., Zeng, C. M., Xu, P., Ning, Y., Dong, M. L., Zhang, W. H., & Yu, G. (2024). Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability. Preprints. https://doi.org/10.20944/preprints202407.1597.v1
Chicago/Turabian Style
Luo, S., Wen-Hua Zhang and Guangliang Yu. 2024 "Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability" Preprints. https://doi.org/10.20944/preprints202407.1597.v1
Abstract
In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for the efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1 and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7, with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10−5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via sequestration of bio-relevant metal ions (i.e. Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared to that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.
Copyright:
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