Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability

Опубликована: Июль 19, 2024

In this work, we report the synthesis of a new thiosemicarbazone-based drug N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring thiazole spectator for efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 2 exhibit dimeric structures ascribed presence di-2-pyridylketone moieties that demonstrate dual functions chelation intermolecular bridging. HL, are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, HuH-7, half maximal inhibitory concentration (IC50) values as low 3.26 nmol/mL (HL), 2.18 (1), 2.54 × 10−5 (2) PLC/PRF/5. While free ligand HL may elicit its anticancer effect via sequestration bio-relevant metal ions (i.e. Fe3+ Cu2+), also capable generating cytotoxic reactive oxygen species (ROS) inhibit cancer proliferation. Our preliminary pharmacokinetic studies revealed oral administration (per os, PO) has significantly longer half-life t1/2 21.61 ± 9.4 h, nearly doubled compared intravenous (i.v.) 11.88 1.66 certifying an effective chemotherapeutic PO administration.

Язык: Английский

Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Moving toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability

Molecules, Год журнала: 2024, Номер 29(16), С. 3832 - 3832

Опубликована: Авг. 13, 2024

In this work, we report the synthesis of a new thiosemicarbazone-based drug N′-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring thiazole spectator for efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 2 exhibit dimeric structures ascribed presence di-2-pyridylketone moieties that demonstrate dual functions chelation intermolecular bridging. HL, 1, are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, HuH-7 half maximal inhibitory concentration (IC50) values as low 3.26 nmol/mL (HL), 2.18 (1), 2.54 × 10−5 (2) PLC/PRF/5. While free ligand HL may elicit its anticancer effect via sequestration bio-relevant metal ions (i.e., Fe3+ Cu2+), also capable generating cytotoxic reactive oxygen species (ROS) inhibit cancer proliferation. Our preliminary pharmacokinetic studies revealed oral administration (per os, PO) has significantly longer half-life t1/2 21.61 ± 9.4 h, nearly doubled compared intravenous (i.v.) 11.88 1.66 certifying an effective chemotherapeutic PO administration.

Язык: Английский