Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Abstract

A novel ligand bearing a central piperidinyl sulfonamide group, N(SO2pip)dpa, and its corresponding Re tricarbonyl complex, [Re(CO)3(N(SO2pip)dpa)]+, have been synthesized in good yield. The methylene CH2 signal seen as a singlet (4.54 ppm) in a 1H NMR spectrum of the ligand in DMSO-d 6 appears as two doublets (5.39, 5.01 ppm) in a spectrum of the [Re(CO)3(N(SO2pip)dpa)]+ complex and confirms the presence of magnetically nonequivalent protons upon coordination to Re. Structural results revealed that the Re–N bond lengths fall within the normal range establishing coordination of ligand to metal. The presence of intraligand π → π ⁎ and n → π ⁎ transitions is indicated by the absorption peaks around 200–250 nm in UV-visible spectra. Absorption peaks in UV-visible spectra around 300 nm for metal complexes were identified as MLCT transitions. The S–N stretch observed as a strong peak at 923 cm−1 for N(SO2pip)dpa appeared at a shorter frequency, at 830 cm−1 in an FTIR spectrum of the [Re(CO)3(N(SO2pip)dpa)]+. The intense fluorescence displayed by the N(SO2pip)dpa ligand has quenched upon coordination to Re. Relatively low IC50 values given by human breast cancer cells, MCF-7, (N(SO2pip)dpa = 139 μM, [Re(CO)3(N(SO2pip)dpa)]+ = 360 μM) indicate that N(SO2pip)dpa and [Re(CO)3(N(SO2pip)dpa)]+ are promising novel compounds that can be further investigated on their usage as potential anticancer agents.

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

“…3. Results and discussion 25 and 1.602 (9) A for N-methyltoluene-psulfonamide and 1.641 (2) A for N,N-dimethyltoluene-p-sulfonamide. 54 However, that has not been depicted by the shortening of S-N bond length in N(SO 2 (2-nap))dpa as that of the most common cases.…”

“…This C6-N2 bond distance (pyridyl N and methylene carbon) of bidentate [PtCl 2 (N(SO 2 pip)dpa)] (1.477 (4) A) complex is not signicantly different to that of tridentate [Re(CO) 3 (-N(SO 2 pip)dpa)] + (1.4615 (16) A) complex. 25 In [PtCl 2 (N(SO 2 (1-nap))dpa)], Pt1-N3 and Pt1-N1 (2.029 A, 2.027 A) bond distances are similar to Pt-N bond lengths in compounds of the type [PtL 2 X 2 ] where L ¼ aniline and X ¼ halides and nitrites, 58 illustrating that the interaction between For the [PtCl 2 (N(SO 2 pip)dpa)] complex, the structural data revealed that the S-O bond lengths (Table 2) are similar to that of S]O in SO 2 (1.43 A). 54 Since the O-S-O angle is as wide as to 121.56 (16) A and the other angles around sulfur atom are slightly smaller in the range of 106.10-108.17 A (Table 3) than the ideal tetrahedral angle (109.5 ), the sulfonyl moiety represents a distorted tetrahedral arrangement around the S atom.…”

“…59 1 H NMR data for the ligands utilized in this study have been previously reported. 25,43 Therefore, the signals related to the platinum complexes were assigned accordingly. 1 H NMR spectra for all compounds are depicted in Fig.…”

“…21 We ourselves have reported on the therapeutic potential of a novel sulfonamide ligand bearing a piperidinyl group and its rhenium complex, [Re(CO) 3 (N(SO 2 pip)dpa)]BF 4 for therapy of human breast cancer, mainly because these types of compounds preferentially bind with sigma receptors. 25 Sulfonamide groups are considered as a pharmacophore because they possess many biological activities such as antimicrobial, 26 anticarbonic anhydrase, 27 antihypersensitive, 28 hypoglycemic 29 activities as well as, most signicantly, anticancer activity. 30 Sulfonamide appended rhenium complexes, for example fac-[Re(CO) 3 (NSO 2 Rdien)]PF 6 (R ¼ dmb, tol) have also been proposed as model systems for radiopharmaceuticals.…”

Synthesis of novel coumarin nucleus-based DPA drug-like molecular entity: In vitro DNA/Cu(II) binding, DNA cleavage and pro-oxidant mechanism for anticancer action

“…However, no progress has been made towards efficient synthesis of coumarin-based dipic derivatives. Dipic ligands such as di(2-picolyl)amine (DPA) and N-substituted DPA derivatives have been investigated for anticancer activities against malignant cells [ 38 , 39 ]. Also, it is important to note that DPA exhibits co-ordination properties in metal complexes [ 40 ].…”