Synthesis, chemical characterization and biological activity of new histone acetylation/deacetylation specific inhibitors: A novel and potential approach to cancer therapy

Pellerito, Ornella; Prinzivalli, Cristina; Foresti, Elisabetta; Sabatino, Piera; Abbate, Michele; Casella, Girolamo; Fiore, Tiziana; Scopelliti, Michelangelo; Pellerito, Claudia; Giuliano, Michela; Grasso, Giulia; Pellerito, Lorenzo

doi:10.1016/j.jinorgbio.2013.04.008

Cited by 12 publications

(16 citation statements)

References 41 publications

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“…This study suggests that toxicologically unrelated organotins are able to upregulate HAT activity resulting in increased histone acetylation [7]. Our previous studies have clearly shown that organotin complexes with valproic acid, a specific histone acetylation/deacetylation inhibitor, show an 80% cell viability reduction after 24 h treatment in HepG2 cells [8]. The specific aim of the present study was to develop potential anti-cancer drugs with tumor regression capacity selecting caffeic acid, catechol-containing coffee polyphenol as a ligand for coordinating dibutyltin(IV) moiety.…”

Section: Introductionmentioning

confidence: 56%

Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy

Pellerito

Morana

Ferrante

et al. 2015

Journal of Inorganic Biochemistry

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Section: Introductionmentioning

confidence: 56%

Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy

Pellerito

Morana

Ferrante

et al. 2015

Journal of Inorganic Biochemistry

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“…In conclusion, the infrared data suggested a monoanionic monodentate coordination of an unidentate ester-type COO group to the R 3 Sn(IV) moiety tin(IV) atom, resulting in tetra-coordinated, monomeric environment (Figure 1). The 1 H and 13 C { 1 H} NMR spectra of the butyric acid and the studied complexes were recorded in CDCl 3 . Data are given in Materials and Methods (Section 3) and resonances for compounds have been assigned.…”

Section: Synthesis and Characterization Of Triorganotin(iv) Butyratesmentioning

confidence: 99%

Tributyltin(IV) Butyrate: A Novel Epigenetic Modifier with ER Stress- and Apoptosis-Inducing Properties in Colon Cancer Cells

et al. 2021

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Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (1H, 13C and 119Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric environment similar to ester. FTIR and NMR findings confirm this structure both in solid state and solution. The antitumor efficacy of the triorganotin(IV) butyrates was tested in colon cancer cells and, among them, tributyltin(IV) butyrate (BT2) was selected as the most efficacious. BT2 induced G2/M cell cycle arrest, ER stress, and apoptotic cell death. These effects were obtained using low concentrations of BT2 up to 1 μM, whereas butyric acid alone was completely inefficacious, and the parent compound TBT was poorly effective at the same treatment conditions. To assess whether butyrate in the coordinated form maintains its epigenetic effects, histone acetylation was evaluated and a dramatic decrease in acetyl-H3 and -H4 histones was found. In contrast, butyrate alone stimulated histone acetylation at a higher concentration (5 mM). BT2 was also capable of preventing histone acetylation induced by SAHA, another potent HDAC inhibitor, thus suggesting that it may activate HDACs. These results support a potential use of BT2, a novel epigenetic modulator, in colon cancer treatment.

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“…[ 41 ] Tri ‐n‐ butyltin valproate ( 92 ) induced apoptosis via both intrinsic and extrinsic pathways by causing mitochondrial transmembrane potential degeneration and the activation of caspase‐8 in HepG2 cells. [ 91 ] Specifically, on a Western blot, a reduction in the intensity of the 57‐ and 32‐kDa bands, corresponding to procaspase‐8 and procaspase‐3, respectively, and the presence of 43‐and 17‐kDa bands, corresponding to cleaved and activated caspase‐8 and caspase‐3, respectively, were observed. Moreover, 92 also acted as a histone deacetylase inhibitor, upregulating acetylated histone H3 after 24 h of treatment.…”

Section: Mechanism Of Action Of Triorganotin Complexesmentioning

confidence: 99%

“…[69] The enhanced cytotoxicity of 90 and 91 was attributed to the lipophilicity of their phenyl groups, which enabled the complexes to bind to biological macromolecules via π-π interactions. The chemical structures of these bimetallic triorganotin complexes (85)(86)(87)(88)(89)(90)(91) are presented in Figure 4. The most potent triorganotin complexes, with IC 50 values in the nM and pM ranges, are tabulated in Table 1.…”

Section: Bimetallic Triorganotin Complexesmentioning

confidence: 99%

Triorganotin complexes in cancer chemotherapy: Mechanistic insights and future perspectives

Anasamy

Chee

Wong

et al. 2020

Applied Organom Chemis

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Current anticancer drug discovery and development efforts are aimed at identifying new complexes that can potently and selectively target DNA and modulate the functions of target proteins. Tin complexes, categorized as monoorganotin (RSnL3), diorganotin (R2SnL2), triorganotin (R3SnL), or tetraorganotin (R4SnL), are one of the most studied complexes in the metal‐based anticancer drug discovery and development field. Among these, diorganotins and triorganotins are widely reported to possess promising anticancer properties, with triorganotins offering several potential advantages over diorganotins, such as a higher total surface area causing higher lipophilicity and hence higher cytotoxicity in cancer cells. However, information on triorganotins' direct therapeutic targets, an in‐depth understanding of their mechanism of action, and useful therapeutic strategies are still lacking. In this review, we discuss the results from in vitro and in vivo mechanistic studies of triorganotin complexes as reported in recent years (2007–2019) and elaborate on the underlying mechanisms that could aid in the identification of triorganotin complex molecular targets. We conclude by identifying present obstacles faced by triorganotin complexes that avert their translation to the clinical phase and current strategies employed to overcome the aforementioned obstacles, and we offer considerations for their future development. These findings are anticipated to stimulate further developments of novel and innovative triorganotin complexes as anticancer drug candidates.

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Synthesis, chemical characterization and biological activity of new histone acetylation/deacetylation specific inhibitors: A novel and potential approach to cancer therapy

Cited by 12 publications

References 41 publications

Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy

Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigenetic regulation as a new and potential approach to cancer therapy

Tributyltin(IV) Butyrate: A Novel Epigenetic Modifier with ER Stress- and Apoptosis-Inducing Properties in Colon Cancer Cells

Triorganotin complexes in cancer chemotherapy: Mechanistic insights and future perspectives

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