Synthesis, characterization and biological studies of dipicolylamine sulfonamide derivatized platinum complexes as potential anticancer agents

Abstract

One novel ligand; N(SO2(2-nap))dpa (94%) and one previously reported ligand; N(SO2pip)dpa) (60%), both containing the dipicolylamine core and a central sulfonamide group and their corresponding novel Pt complexes, [PtCl2(N(SO2(2-nap))dpa)] (68%), [PtCl2(N(SO2pip)dpa)] (90%) have been synthesized in good yield and high purity. X-ray crystallography, 1H NMR, FT-IR and UV-Vis spectroscopies were used to characterize the synthesized compounds. 1H NMR studies revealed that all the peaks of the ligand spectrum have shifted more downfield upon binding to the metal precursor. Structural results for [PtCl2(N(SO2(2-nap))dpa)] and [PtCl2(N(SO2pip)dpa)] revealed indisputably that platinum has coordinated to the pyridyl nitrogen of the ligand and that Pt–Npyridyl bond lengths fall within the normal range. The methylene protons observed as singlets at 4.60 ppm and 4.54 ppm in 1H NMR spectra of N(SO2(2-nap))dpa and N(SO2pip)dpa ligands, respectively appear as two doublets (6.18 ppm and 5.14 ppm, 6.06 ppm and 5.33 ppm) in the corresponding metal complexes in DMSO-d6 and confirm the presence of magnetically nonequivalent protons upon coordination of ligand to Pt. FTIR data indicate that the stretching vibration frequency of S-N bond (923 cm-1) for both ligands remain unchanged upon complexation as expected for the bidentate coordination mode. The presence of high energy intraligand 𝜋 → 𝜋∗ transitions of compounds is indicated by the absorption peaks approximately in the range of 200–250 nm in UV-visible spectra. Sulforhodamine B assay was used for obtaining the IC50 values of ligands and corresponding metal complexes. All four compounds have shown anticancer activity against human breast cancer cells, MCF-7. N(SO2(2-nap))dpa ligand and [PtCl2(N(SO2(2-nap))dpa)] complex have shown acute anticancer activity at IC50 of 34.88 mg/L and 0.1810 mg/L respectively, indicating these are promising novel compounds that can be further investigated on their usage as potential anticancer agents.