o-Vanillin Derived Schiff Bases and Their Organotin(IV) Compounds: Synthesis, Structural Characterisation, In-Silico Studies and Cytotoxicity

Abstract

Six new organotin(IV) compounds of Schiff bases derived from S-R-dithiocarbazate [R = benzyl (B), 2- or 4-methylbenzyl (2M and 4M, respectively)] condensed with 2-hydroxy-3-methoxybenzaldehyde (oVa) were synthesised and characterised by elemental analysis, various spectroscopic techniques including infrared, UV-vis, multinuclear (1H, 13C, 119Sn) NMR and mass spectrometry, and single crystal X-ray diffraction. The organotin(IV) compounds were synthesised from the reaction of Ph2SnCl2 or Me2SnCl2 with the Schiff bases (S2MoVaH/S4MoVaH/SBoVaH) to form a total of six new organotin(IV) compounds that had a general formula of [R2Sn(L)] (where L = Schiff base; R = Ph or Me). The molecular geometries of Me2Sn(S2MoVa), Me2Sn(S4MoVa) and Me2Sn(SBoVa) were established by X-ray crystallography and verified using density functional theory calculations. Interestingly, each experimental structure contained two independent but chemically similar molecules in the crystallographic asymmetric unit. The coordination geometry for each molecule was defined by thiolate-sulphur, phenoxide-oxygen and imine-nitrogen atoms derived from a dinegative, tridentate dithiocarbazate ligand with the remaining positions occupied by the methyl-carbon atoms of the organo groups. In each case, the resulting five-coordinate C2NOS geometry was almost exactly intermediate between ideal trigonal-bipyramidal and square-pyramidal geometries. The cytotoxic activities of the Schiff bases and organotin(IV) compounds were investigated against EJ-28 and RT-112 (bladder), HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast) A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic) cancer cell lines and one normal breast cell line (MCF-10A). Diphenyltin(IV) compounds exhibited greater potency than either the Schiff bases or the respective dimethyltin(IV) compounds. Mechanistic studies on the action of these compounds against bladder cancer cells revealed that they induced the production of reactive oxygen species (ROS). The bladder cancer cells were apoptotic after 24 h post-treatment with the diphenyltin(IV) compounds. The interactions of the organotin(IV) compounds with calf thymus DNA (CT-DNA) were experimentally explored using UV-vis absorption spectroscopy. This study revealed that the organotin(IV) compounds have strong DNA binding affinity, verified via molecular docking simulations, which suggests that these organotin(IV) compounds interact with DNA via groove-binding interactions.

Homoleptic tin(IV) compounds containing tridentate ONS dithiocarbazate Schiff bases: Synthesis, X-ray crystallography, DFT and cytotoxicity studies

“…The infrared spectra of 1-6 were measured in the range of 4000 to 280 cm − L3were not observed in the IR spectra due to the intra-and inter-molecular interactions between the molecules, which was similar to that reported in our previous work [36].…”

“…The important signals observed in the range of 9.51-9.61 ppm and 13.32-13.41 ppm were assigned to the proton of -OH and -NH in the Schiff base, respectively, which were reported in our previous publications [36]. Both of the signals disappeared in the 1 H NMR of the tin(IV) compounds indicating the deprotonation of the -OH and -NH groups upon complexation.…”

“…In view of all these findings and in continuation of our previously reported research work [36] on the chemistry, therapeutic potential and structure-activity relationship of tin(IV) compounds coordinated with two dithiocarbazate Schiff bases, we report here the synthesis of six new octahedral tin(IV) compounds derived from 2-hydroxy-3-methoxybenzaldehyde and 2,3-dihydroxybenzaldehyde dithiocarbazate. The compounds were characterised by FT-IR, multinuclear NMR ( 1 H, 13 C and 119 Sn), mass spectroscopy, UV-vis and density functional theory (DFT) calculations.…”

A Ternary Nickel(II) Schiff Base Complex Containing Di-Anionic and Neutral Forms of a Dithiocarbazate Schiff Base

“…These Schiff bases can be modified by incorporating various types of substituents to moderate/enhance their biological and pharmacological activities [7][8][9]. Relevant to the present study, recent investigations of the Schiff base derived from the condensation of S-2-methylbenzyldithiocarbazate and 2-hydroxy-3-methoxybenzaldehyde showed these molecules, when complexed to diorganotin centers, to exhibit good potency against a panel of cancer cells [10]. The bioactivities of the Schiff bases have also been reported to be enhanced by the coordination with transition metal ions such as nickel, possibly due to their reduced polarity and increased lipophilicity required for easier entry into the permeable membranes of cells and microbes [11].…”

“…The bioactivities of the Schiff bases have also been reported to be enhanced by the coordination with transition metal ions such as nickel, possibly due to their reduced polarity and increased lipophilicity required for easier entry into the permeable membranes of cells and microbes [11]. In view of ongoing interest in the structures and biological activities of this class of Schiff base and their coordination complexes, the synthesis, spectroscopic characterization, and X-ray crystal structure determination of the title Ni II complex, Ni(L)(LH 2 ) (1), and Scheme 1, are described; the systematic name for LH 2 base derived from the condensation of S-2-methylbenzyldithiocarbazate and 2-hydroxy-3-methoxybenzaldehyde showed these molecules, when complexed to diorganotin centers, to exhibit good potency against a panel of cancer cells [10]. The bioactivities of the Schiff bases have also been reported to be enhanced by the coordination with transition metal ions such as nickel, possibly due to their reduced polarity and increased lipophilicity required for easier entry into the permeable membranes of cells and microbes [11].…”