In Vivo Anticancer Activity of a Nontoxic Inert Phenolato Titanium Complex: High Efficacy on Solid Tumors Alone and Combined with Platinum Drugs

Overview

Journal ChemMedChem

Specialties Chemistry
Pharmacology

Date 2018 Sep 12

PMID 30203598

Citations 7

Authors

Nitzan Ganot

Ori Briaitbard

Asaad Gammal

Joseph Tam

Jacob Hochman

Edit Y Tshuva

Affiliations

Soon will be listed here.

Abstract

Due to the toxicity of platinum compounds used in the clinic as anticancer chemotherapies, titanium serves as a safe and attractive alternative. Lately, we introduced a new family of Ti complexes based on readily available phenolato ligands, demonstrating incredibly high hydrolytic stability, with the lead compound phenolaTi demonstrating wide cytotoxic activity toward the NCI-60 panel of human cancer cell lines, with an average GI value of 4.7±2 μm. Herein, we evaluated in vivo: a) the safety, and b) the growth inhibitory capacity (efficacy) of this compound. PhenolaTi was found to be effective in vivo against colon (CT-26) and lung (LLC-1) murine cell lines in syngeneic hosts and toward a human colon cancer (HT-29) cell line in immune-deficient (Nude) mice, with an efficacy similar to that of known chemotherapy. Notably, no clinical signs of toxicity were observed in the treated mice, namely, no effect on body weight, spleen weight or kidney function, unlike the effects observed with the positive control Pt drugs. Studies of combinations of phenolaTi and Pt drugs provided evidence that similar efficacy with decreased toxicity may be achieved, which is highly valuable for medicinal applications.

Citing Articles

A Comprehensive Review on the Development of Titanium Complexes as Cytotoxic Agents.

Kumar N, Kaushal R, Awasthi P Curr Top Med Chem. 2024; 24(24):2117-2128.

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Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid.

Li S, Zhang X, Zhao T, Liu N, Zhang Y, Wang P J Biol Inorg Chem. 2024; 29(3):315-330.

PMID: 38722397 DOI: 10.1007/s00775-024-02059-9.

Bioactive O^N^O^ Schiff base appended homoleptic titanium(iv) complexes: DFT, BSA/CT-DNA interactions, molecular docking and antitumor activity against HeLa and A549 cell lines.

Thanigachalam S, Pathak M RSC Adv. 2024; 14(19):13062-13082.

PMID: 38655487 PMC: 11034360. DOI: 10.1039/d3ra08574k.

Titanium complexes affect biofilm formation.

Hayet S, Ghrayeb M, Azulay D, Shpilt Z, Tshuva E, Chai L RSC Med Chem. 2023; 14(5):983-991.

PMID: 37252093 PMC: 10211322. DOI: 10.1039/d3md00075c.

Synthesis of asymmetrical diaminobis(alkoxo)-bisphenol compounds and their C-symmetrical mono-ligated titanium(iv) complexes as highly stable highly active antitumor compounds.

Nahari G, Tshuva E Dalton Trans. 2021; 50(19):6423-6426.

PMID: 33949509 PMC: 8130176. DOI: 10.1039/d1dt00219h.

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