Antitumor Platinum(II) Complexes Containing Platinum-Based Moieties of Present Platinum Drugs and Furoxan Groups as Nitric Oxide Donors: Synthesis, DNA Interaction, and Cytotoxicity

Abstract

Six novel platinum(II) complexes 1-6 bearing different furoxan moieties as nitric oxide (NO) donors have been designed, synthesized, and characterized by elemental analysis and (1)H NMR, IR, and ESI-MS spectroscopy. The furoxan groups were introduced to the platinum complexes to release NO, which may take synergic action with the platinum-based moieties on the tumor cells. It was found that all compounds exhibited considerable cytotoxicity against human HCT-116 and SGC-7901 cell lines via DNA binding together with NO-releasing features, especially for compound 3. This finding is in accordance with the previous reports that NO hybrids show higher cytotoxicity against colon cancer cell lines compared with their parent compounds.

Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity

“…IR spectra (Nujol) were registered with a Shimadzu FTIR-8300 instrument. 1 H NMR spectra were recorded on a Bruker 300 Avance spectrometer, operating at 300 MHz, with tetramethylsilane (TMS) as an internal standard. The molar conductivities for all complexes were determined in DMSO at 10 −3 M at 25°C with a Crison GLP 31 Model Conductometer.…”

“…Many efforts have been dedicated to explain the factors related to the anticancer activity of cisplatin and different platinum compounds [1,2] and although the molecular mechanistic studies of cisplatin and analogs have been largely developed, the cellular response to these compounds is still poorly understood [3,4].…”

Nitric oxide donor hybrid compounds as promising anticancer agents

“…The research of Zhao J et al found that hybrids of furoxan and Pt (4a, 4b, 4c, Figure 1) were more effective against gastric carcinoma cell line SGC-7901 and colonic carcinoma cell line HCT-116 in vitro compared with carboplatin, oxaliplatin alone or a combination of oxaliplatin and furoxan (23). Moreover, it was demonstrated that the hybrids had better stability and less adverse effects than Platinum agents (24).…”

Synthesis, structural characterization and cytotoxic activity of heterocyclic compounds containing the furoxan ring

“…), [7][8][9] including the 1,2,5-oxadiazole 2-oxides (furoxans) which are capable of exogenous NO release at the presence of thiol cofactors. 10,11 Furoxans comprise a valuable class of five-membered heterocycles and can serve as a privileged motif in medicinal and pharmaceutical chemistry owing to their significant biological activities, for example neuroprotective and precognitive, 12 cytotoxic, 13,14 antihelmintic, 15 antibacterial 16 and fungicidal 17 , connected with the high capacity of furoxans to produce a large flux of NO. It was established that NO exerts a cytotoxic effect at high concentrations, while low levels of NO are potentially protective, particularly in the CNS.…”

“…Various derivatives of these types of heterocycle have previously revealed cytotoxic activity: 1,2,4-oxadiazole, 31 1,2,4-triazine, 32,33 1,2,3-triazole, 34 and furoxan itself. 13,14 Heterocyclic motifs, namely quinolines 35 and pyridines, 36 connected to the furoxan ring through O-bridges, are also found in compounds possessing cytotoxic activity.…”