Binuclear diphenyltin(IV)dithiocarbamate complexes bearing functionalized linkers: Synthesis, spectral characterization, DFT andin vitroanticancer activity (original) (raw)
Related papers
Applied Organometallic Chemistry, 2003
- have been synthesized in 1 : 1 molar ratio by the reaction of Bu 2 SnO with the respective dipeptide under azeotropic removal of water. Triphenyltin glycylleucinate was obtained by reacting Ph 3 SnCl and sodium glycylleucinate with filtration of NaCl formed. The bonding and coordination behaviour in these derivatives are discussed on the basis of IR, multinuclear 1 H, 13 C and 117 Sn magnetic resonance and 119 Sn Mössbauer spectroscopic studies. These investigations suggest that all the ligands in R 2 SnL act as dianionic tridentates coordinating through the COO − , NH 2 and N peptide groups, whereas in Ph 3 Sn(HL) the ligand acts as a bidentate coordinating through the COO − and NH 2 groups. The 119 Sn Mössbauer studies, together with the NMR data, indicate that, for the 1 : 1 monomeric derivatives, the polyhedron around tin in R 2 SnL is a trigonal bipyramid with the butyl groups and N peptide in the equatorial positions, while the axial positions are occupied by a carboxylic oxygen and the amino nitrogen atom. In Ph 3 Sn(HL) the structure is intermediate between pseudotetrahedral and cis-trigonal bipyramidal, with the N amino and two phenyl groups in the equatorial plane and the carboxylate oxygen and the third phenyl group in axial positions. All the complexes have been screened against seven cancer cell lines of human origin, viz. MCF-7, EVSA-T, WiDr, IGROV, M19, MEL A498 and H226. Ph 3 Sn(HL) displays the lowest ID 50 values of the tin compounds tested and reported in this paper. Its activity is comparable to those of methotrexate and 5-fluorouracil. All the di-n-butyltin compounds exhibit lower in vitro anti-tumour activities than Ph 3 Sn(HL); however, they do provide significantly better activities than etoposide and cis-platin.
Organo-tin antitumor compounds: Their present status in drug development and future perspectives
Inorganica Chimica Acta, 2014
Toxicity-related problems, drug resistance and broad spectrum of action have hindered the success pathway of platinum antitumor chemotherapeutic drugs, although the survival rates for patients suffering from solid cancers treated by platinum drugs, notably 'cisplatin' is considerably high. Therefore, many non-platinum metal-based chemical entities are gaining attention and have also entered preclinical testing and clinical trails, yet at a later stage they fail to qualify as drugs and consequently, there is lot of setback to pharmaceutical R&D's. Thus, there is a quest for the design of novel metal-based efficacious cancer chemotherapeutics exhibiting a different mode of action of cell death at the molecular level. Among the non-platinum metal-based drugs, organotin compounds have proven their worth in effective management of toxicity issues and specific targeted drug uptake only by the cancerous cells leaving the healthy cells unaffected (apoptosis). Herein, we reflect the progress made in the past decade by organotin compounds as antitumor chemotherapeutic agents (it was observed that more than 50% of organotin compounds show high cytotoxic activity but surprisingly have not entered clinical trails) and explore the landmarks for their future projections in drug industry.
Comptes Rendus Chimie, 2015
Cancer has become a leading cause of death worldwide, which is responsible for 7.6 million cancer deaths according to GLOBOCAN survey conducted in 2008. The exploration of cis-platin analogues (carboplatin, lobaplatin, nedaplatin, oxaliplatin) and their incorporation to the treatment of cancer patients has further led interest in exploring metal-based anticancer drugs. The current study describes the synthesis of two new tetracoordinated mono-and tetranuclear organotin(IV) carboxylate complexes and their in vitro anticancer studies. Each one of the complexes (1-2) has been characterized by analytical (micro-and gravimetric analysis) and spectroscopic (FTIR, 1 H, 13 C, 119 Sn-NMR) techniques. Furthermore, molecular structures of 1 and 2 were elucidated using X-ray crystallography. The characterization data showed that the coordination took place via oxygen atoms from the carboxylate anions to generate 1 as an organodistannoxane dimer and 2 as a mononuclear complex. Exceptionally, the NMR spectroscopic and X-ray crystallographic study showed that acetone molecules also took part in crystallizing 2. Both complexes were tested against three cancerous (colon cancer HCT 116, breast cancer MCF 7, leukemia K562) and one non-cancerous (3T3-L1) cell lines. Both complexes showed same IC 50 value (0.2 mM) against HCT 116, whereas for the other two cancer cell lines (MCF 7 and K562) and a normal cell line (3T3-L 1 ), 2 showed results better than 1. Importantly, the complexes showed exceptional activity against MCF 7 and K562 cell lines and the IC 50 values were calculated in nanomoles (MCF 7, IC 50s = 86.5 and 53.4 nM; K 562, IC 50s = 22.9 and 49.6 nM for 1 and 2, respectively). Both, 1 and 2, showed IC 50 values many times better than the standard drugs (5-FU, Tamoxifen, betulinic acid and cis-platin) used. Compared to cancerous cell lines, the complexes showed mild toxicity against normal cells (3T3-L1). Overall, two remained relatively effective.
There is a growing interest in the cancer cell growth inhibitory effects of organotin (IV) compounds and, accordingly, a new series of dimethyl-, di-(n-butyl)-, diphenyl-and chloro-phenyl tin(IV) complexes with a Schiff base core were prepared. Their binding to DNA was assessed by UV thermal denaturation showing no interaction and by UVevis titration exhibiting moderate interaction by intercalation. Complexes having n-butyl substituents were more potent and cytotoxic against human leukemia, breast and cervical cancer cell lines than other organotin(IV) complexes tested. Unfortunately, some of these compounds showed similar cytotoxicity in a non-cancerous cell line. We may conclude that cytotoxic activity was dependent on the nature (lipophilicity and size, according to the structure-activity relationship studies) and substitution pattern on the different structures. These results may aid in the rational design of metallodrugs, expanding the scope of organotin complexes in formulating new metal based drugs with dibutyl moieties.