Organotin(IV) complexes of NSAID, ibuprofen, X‐ray structure of Ph₃Sn(IBF), binding and cleavage interaction with DNA and in vitro cytotoxic studies of several organotin complexes of drugs

Abstract

This study encompasses the synthesis and characterization of organotin(IV) derivatives of non‐steroidal anti‐inflammatory drug ibuprofen (IBF), viz. [(Me3Sn)(IBF)] (1), [(Bu3Sn)(IBF)] (2), [Ph3Sn(IBF)] (3), {[Me2Sn(IBF)]2O}2 (4) and [Bu2Sn(IBF)2] (5). The crystal structure of complex 3, [Ph3Sn(IBF)], indicates a highly distorted tetrahedral (td) geometry with anisobidentate mode of coordination of the carboxylate group with tin atom, and a similar structure has been proposed for other two triorganotin(IV) derivatives. Moreover, the DFT (density functional theory) calculation and other studies have verified a dimer distannoxane type of structure for complex 4, {[Me2Sn(IBF)]2O}2. Complex 5 has been found to exhibit a highly distorted octahedral geometry around the tin atom. To investigate the DNA binding profile of the synthesized complexes, viscosity measurement, UV–vis and fluorescence titrations were performed, which revealed an intercalative type of binding with DNA for IBF and complex 5 and external binding in case of the complexes 1 and 2; complexes 3 and 4 could not be studied owing to their insufficient solubility in tris buffer. Plasmid DNA fragmentation studies of IBF and complexes 1, 2 and 5 indicate that they cleaved the pBR322 plasmid potentially. Further, the drugs IBF {2‐[4‐(2‐methylpropyl)phenyl]propanoic acid}, MESNA (sodium 2‐mercaptoethane‐sulfonate), warfarin [2H‐1‐benzopyran‐2‐one,4‐hydroxy‐3‐(3‐oxo‐1‐phenylbutyl)], sulindac (2‐{5‐fluoro‐1‐[(4‐methanesulfinylphenyl) methylidene]‐2‐methyl‐1H‐inden‐3‐yl}acetic acid) and their corresponding organotin(IV) complexes 1–19 (complexes 6–19 were synthesized/reported previously) were screened in vitro for cytotoxicity against human cancer cell lines viz. DU145 (prostate cancer), HCT‐15 (colon adenocarcinoma), Caco‐2 (colorectal adenocarcinoma), MCF‐7 (mammary cancer), LNCaP (androgen‐sensitive prostate adenocarcinoma) and HeLa (cervical cancer), through MTT reduction assay and the cause of cell death was investigated through acridine orange/ethidium bromide staining of cells and DNA fragmentation assay. The probable structure–cytotoxicity relationship is also discussed. The major role of apoptosis along with small necrosis was also validated by flow cytometry assay using annexin V–fluorescein isothiocyanate and propidium iodide analysis.

A Surface Morphological Study, Poly(Vinyl Chloride) Photo-Stabilizers Utilizing Ibuprofen Tin Complexes against Ultraviolet Radiation

“…Furthermore, the presence of peaks was demonstrated between 443 and 482 cm −1 , and 543 and 555 cm −1 , which are related to stretching Sn-O bond frequency, and stretching Sn-C bond frequency, respectively. This is obvious evidence regarding the complex formation [35].…”

“…Furthermore, the presence of peaks was demonstrated between 443 and 482 cm −1 , and 543 and 555 cm −1 , which are related to stretching Sn-O bond frequency, and stretching Sn-C bond frequency, respectively. This is obvious evidence regarding the complex formation [35]. The FTIR spectrum for Ibuprofen was compared with the spectra of organotin(IV) complexes to clarify the bonding sites of ligand molecules when coordinated with organotin(IV) compounds.…”

Design, synthesis and cytotoxic evaluation in tumor cell lines of organotin(IV) complexes with heteroditopic hydroxo-carboxylato polyaromatic ligands¶

“…However, the variations in the in vitro cytotoxicity among 1 and 2 across tumor cell lines could also be related to a different kinetic and mechanistic behavior. Recently, the cytotoxicity for nBu 3 Sn(ibuprofen) and Ph 3 Sn(ibuprofen) were reported; however, in practice, the results should not be compared directly, since these were investigated using DU145 (prostate cancer), HCT-15 (colon adenocarcinoma), Caco-2 (colorectal adenocarcinoma) human cancer cell lines [55]. The observed results convincingly support the view that compounds 1 and 2 are potent cytotoxic agents and deserve further investigation as potential anticancer agents.…”

NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─Structural Modulation, Mechanisms of Action, and Bright Future

“…Numerous studies have demonstrated that metal-NSAID complexes, including zinc­(II)-NSAIDs, − iridium­(III)-aspirin, ruthenium­(II)-NSAIDs, − nickel­(II)-NSAIDs, silver­(I)-NSAIDs, − manganese­(II)-NSAIDs, , and organotin­(IV)-NSAIDs, also exhibit potent cytotoxic activity against several cancer cells. The most likely modes of action of these complexes are increase of COX-2 selectivity, , induction of ROS, interaction with serum albumins, and intercalation of DNA .…”