In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines

Abstract

The synthesis of novel triphenyltin(IV) compounds, Ph3SnLn (n = 1–3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC50 values ranging from 0.100 to 0.758 µM. According to the CV assay (IC50 = 0.218 ± 0.025 µM), complex Ph3SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph3SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph3SnL1 induces caspase-independent apoptosis in MCF-7 cells.

Recent Studies on Cancer Cell's Inhibition by Organotin (IV) Materials: An Overview

“…These derivatives can exhibit improved pharmacokinetic and pharmacodynamic properties, leading to increased efficacy and reduced side effects [31]. The paper published by Pantelić et al presents a comprehensive study on the potential antiproliferative effects of newly synthesized derivatives of organotin (IV) carboxylate compounds as shown in Figure 5 [32]. The research focuses on evaluating the cytotoxicity and growth inhibition properties of these compounds against a panel of human cancer cell lines.…”

“…The propanoic acid derivatives used in the study were chosen due to their known anticancer activities, and their incorporation into organotin (IV) complexes aimed to enhance their therapeutic potential. The authors performed a series of in vitro experiments, utilizing various techniques such as MTT assay, cell viability assessment, and morphological observations to evaluate the efficacy of the novel compounds [32]. The results demonstrated significant antiproliferative activity against a range of human cancer cell lines, including breast, lung, colon, and prostate cancer.…”

Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells

“…The best cytotoxic activity of triorganotin(IV) compounds is attributed to their highest lipophilicity, the availability of coordination positions at the tin center and their affinity to proteins [ 3 , 15 , 16 , 17 ]. The organotin(IV) carboxylates have shown the highest anticancer activity in comparison with organotin(IV) thiolates and dithiocarbamates [ 18 ]. In terms of advantages over cisplatin, organotin(IV) compounds are cheaper and widely available, and they are less toxic and induce apoptosis at low doses so the cells do not develop resistance to them [ 13 , 19 , 20 ].…”

Triphenyltin(IV) Carboxylates with Exceptionally High Cytotoxicity against Different Breast Cancer Cell Lines

“…These complexes have shown excellent cytotoxicity with IC 50 values of 0.10–0.76 µM. Once again, triphenyltin(IV) oxaprozinate has demonstrated greatest cytotoxicity towards the cancer cell line MCF-7 [ 56 ]. Several organotin(IV) indomethacinates have also been prepared; tri- n -butyltin(IV) and triphenyltin(IV) indomethacinate exhibited cytotoxic activity against the SK-LU-1 lung adenocarcinoma and the cervical cancer HeLa cells [ 57 ].…”