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Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Moving toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability.
- Source :
- Molecules; Aug2024, Vol. 29 Issue 16, p3832, 15p
- Publication Year :
- 2024
-
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 efficient coordination with Cu(II) to give [CuCl(L)]<subscript>2</subscript> (1) and [Cu(NO<subscript>3</subscript>)(L)]<subscript>2</subscript> (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 (IC<subscript>50</subscript>) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10<superscript>−5</superscript> nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via the sequestration of bio-relevant metal ions (i.e., Fe<superscript>3+</superscript> and Cu<superscript>2+</superscript>), 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 t<subscript>1/2</subscript> of 21.61 ± 9.4 h, nearly doubled as compared with that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 29
- Issue :
- 16
- Database :
- Complementary Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 179381561
- Full Text :
- https://doi.org/10.3390/molecules29163832