Platinum Complexes with 5‐Methyl‐5(4‐pyridyl)hydantoin and Its 3‐Methyl Derivatives: Synthesis and Cytotoxic Activity – Quantitative Structure‐Activity Relationships

Abstract

3,5-Dimethyl-5-(4-pyridyl)hydantoin (L) and its platinum(II) and platinum(IV) complexes with the general formula cis-[PtL(2) X(2) ] · n H(2) O and [PtL(2) Cl(4) ], where XCl, I and n = 2-4 were synthesized. A new Pt(IV) complex with 5-methyl-5-(4-pyridyl)hydantoin (L') with the formula cis-[Pt(L')(2) Cl(2) (OH)(2) ] · 5 H(2) O was also synthesized. The novel compounds were characterized by elemental analysis, IR, (1) H-, (13) C-, (195) Pt-NMR spectra and molar conductivity. The cytotoxic effects of these complexes were examined on three human tumor cell lines by MTT-dye reduction assay. These four new Pt(II) and Pt(IV) complexes and a set of another twelve Pt(II), Pt(IV), and Pd(II) complexes previously synthesized and tested were compiled and a QSAR model was derived in order to direct the further rational synthesis.

Design, synthesis and comparative cytotoxic investigation of platinum(II) complexes with some derivatives of 5-methyl-5-(4-pyridyl)hydantoin

“…This indicates that the pyridine nitrogen atom participates in the coordination with platinum in all new platinum(II) complexes. These observations are in accordance with previously studied and published Pt(II) complexes with 3-amino-5-methyl-5-(4-pyridyl)hydantoin (1), 5-methyl-5-(4-pyridyl)hydantoin (2), 3,5-dimethyl-5-(4-pyridyl)hydantoin (3) [20,26,27].…”

“…Structure-cytotoxicity relationship studies revealed that for many compounds increased lipophilicity is often accompanied by increased cytotoxicity [25]. Taking into account our previous experience with cytotoxic platinum(II) complexes, carrying hydantoin ligands [26,27] and the approach for increasing lipophilicity via alkylation, herein we have prepared more lipophilic 3-subsituted-5-methyl-5-(4-pyridyl) hydrations and their Pt(II) complexes. The present study represents the synthesis, physicochemical evaluation and pharmacological investigation of three new Pt(II) complexes with 3-ethyl-5-methyl-5-(4-pyridyl)hydantoin (4), 3-propyl-5-methyl-5-(4-pyridyl)hydantoin (5) and 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin (6) with general formula cis-[Pt(L) 2 Cl 2 ].…”

“…Two new mixed am(m)ine Pt(II) complexes with 3-propyl-5-methyl-5-(4-pyridyl)hydantoin (L5) as ligand in cis-and trans-position with chemical formulae cis-[Pt(NH 3 )(L5)Cl 2 ] (5a) and trans-[Pt(NH 3 )(L5)Cl 2 ] (5b) were also synthesized and studied. All obtained platinum complexes were chemically and pharmacologically examined in comparison with previously synthesized and published Pt(II) complexes with 3-amino-5-methyl-5-(4-pyridyl)hydantoin, 5-methyl-5-(4-pyridyl)hydantoin, 3,5-dimethyl-5-(4-pyridyl)hydantoin, (1-3) and the clinically applied drug cisplatin [20,26,27]. General scheme of the investigated compounds is shown in Fig.…”

Supramolecular interaction of transition metal complexes with albumins and DNA: Spectroscopic methods of estimation of binding parameters

“…Many Pt(II) and Pt(IV) compounds are investigated in vitro for antitumor effects. [93][94][95][96] At present, it is a rule to consider that the antitumor activity of the platinum-containing anticancer preparations is associated with DNA platination. [97] The antitumor properties of Pt(II) complexes are supposed to be strongly dependent on the character of bond between different ligands and the metal.…”

Synthesis, DFT calculations and cytotoxic investigation of platinum complexes with 3-thiolanespiro-5′-hydantoin and 4-thio-1H-tetrahydropyranespiro-5′-hydantoin

“…Over the last few years we have been synthesized and studied for cytotoxicity in vitro some Pt(II) and Pt(IV) complexes with different hydantoin and spirohydantoin derivatives [16][17][18]. Some of them have similar cytotoxic activity to referent antitumor agent cisplatin.…”