Synthesis, Cytotoxic Effect, and Structure−Activity Relationship of Pd(II) Complexes with Coumarin Derivatives

Abstract

We report the influence of the substituent at the N atom of the ligands on the synthesis, biological activity, and stability of Pd(II) complexes of the general formula PdL(2). The compounds adopt a cis or trans configuration with respect to the substituent at the nitrogen atom. Sterically hindered substituents promote the formation of trans isomers, whereas when the nitrogen atom is unsubstituted, cis isomers are formed. The compounds were characterized by elemental analysis, infrared and 1H NMR spectroscopies, and electrospray mass spectrometry. The complexes were also studied using X-ray diffraction and computational DFT methods. Both complexes cis-3a and trans-3c exhibit square-planar geometries around the Pd(II) atom. The cytotoxic effects of these complexes were examined on two human leukemia cell lines, HL-60 and NALM-6. Pd complex cis-3a showed significant cytotoxic activity. The effects exhibited by this complex were comparable to those reported for carboplatin. Loigand 2a was not cytotoxic. Computational analysis carried out at the PB/B3LYP/LACVP**//mPW1PW91/LanL2DZ level showed excellent correlation between the energy difference of the cis and trans isomers and the cytotoxic activity, rendering computations a useful predictive tool for the design of new drugs.

Biological Properties Of Benzopyran-Based Platinum (Ii) Complexes

“…Chromono-2(3)-carboxylic acids and their derivatives have antiarrythmic properties. Another derivative of 2-phenylchromone There have been reports of studies whereby complexes of metals with flavone derivatives were obtained or with other ligands with a similar structure (19)(20)(21)(22)(23)(24)(25)(26)(27). In these studies, the compounds displayed high biological activity which potentially lead to their application in medicine.…”

Chemistry of 3-carbonyl-2-methyl-4-oxo-4H-1-benzopyrans

“…[66][67][68][69] This four co-ordinated Pd(II) complex 117 exists in cis-isomeric form for the ligand L (R = H) and trans-form for L (R = other than H). 67,68 Cytotoxic effects of the diones 115 and several of their Pd(II) complexes have been assessed against two leukemia cell lines HL-60 and NALM-6. On treatment with RNH 2 (R = H, Me, PhCH 2 , hexyl, cyclohexyl etc.…”

Synthesis, Structure, Protolytic Properties, Alkylating and Cytotoxic Activity of Novel Platinum(II) and Palladium(II) Complexes with Pyrazole‐Derived Ligands

“…It was suggested that their biological activity depends on the nature of the ligand, the type of counterion used and the configuration of the complex. [18] For many years the research in our laboratory has been directed towards the synthesis of chromone (benzo-γ-pyrone) and coumarin (benzo-α-pyrone) derivatives and the study of their reactivity towards nucleophilic reagents containing nitrogen, oxygen, sulfur and carbon. [19] In particular, in protolytic solvents at room temperature chromones have been converted efficiently into enamine-type compounds with a typical lemon-yellow colour.…”