The potential anticancer activities of platinum(II) complexes with tridentate N'N'N' pincer ligands

Abstract

Treatment of cis/trans-[PtCl₂(N≡CR)₂] 1 (R = CH₃ (1a), C₂H₅ (1b), C₆H₅ (1c), CH₂C₆H₄(p-CH₃) (1d)) with 1,3-diiminoisoindoline 2 gives access to the corresponding symmetrical (1,3,5,7,9-pentaazanona-1,3,6,8-tetraenato) platinum(II) complexes [PtCl{NH=C(R)N=C(C₆H₄)NC=NC(R)=NH}] 3a-d, in good yields (65–77%). The compounds 3a-d have been characterized by IR, ¹H, ¹³C and DEPT-135 NMR spectroscopies, ESI-MS and elemental analyses. GIAO/DFT studies have been performed to confirm the molecular structure of the platinum(II)-pincer 3d by comparing the experimental and theoretical ¹H and ¹³C NMR chemical shifts, and it has shown good correlations between experimental and calculated chemical shifts for proton and carbon with correlation coefficients of 0.9947 and 0.9968, respectively. Molecular electrostatic potential is used to investigate the nucleophilic or electrophilic regions in the molecule 3d. The antimicrobial activities of compounds 3a-d are determined against different bacterial pathogens and yeasts. No toxicity is recorded against Artemia saline as a test organism for 3a-c, while moderate toxicity is found for 3d at 0.62 µM. Comparable antitumor activities are found for 3a-d against human colon HCT116 and human breast (MCF-7) cancer cell lines. The complexes 3a-d have shown good binding affinities to ct-DNA in the range of 6.00´10⁵ to 8.33´10⁵ and the conducted molecular docking studies suggest an intercalation mode of binding with DNA by the isoindole fragment of the ligands. Overall, this class of tridentate ligands have shown good potential in designing platinum(II) complexes with promising biological and anticancer activities. Moreover, the presence of the side chains on the ligands provides great design flexibility by introducing some chemical and/or physical characteristics.