TY - JOUR
T1 - Cytotoxic homoleptic Ti(iv) compounds of ONO-type ligands
T2 - synthesis, structures and anti-cancer activity
AU - Manne, Rajesh
AU - Miller, Maya
AU - Duthie, Andrew
AU - Guedes Da Silva, M. Fátima C.
AU - Tshuva, Edit Y.
AU - Basu Baul, Tushar S.
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2019
Y1 - 2019
N2 - Eight Ti(iv) compounds 1-8, of the type [Ti(L n ) 2 ] where L n is a variously substituted dianionic tridentate acylhydrazone, were synthesized by reacting the appropriate hydrazide with 2-hydroxybenzaldehyde or 2′-hydroxyacetophenone and titanium(iv) tetra(isopropoxide) in a 2 : 2 : 1 molar ratio. The solid-state structures of 1-6 and 7·CH 2 Cl 2 were deduced from the single crystal X-ray diffraction data, which indicated that each L 2− ligand is fully deprotonated and coordinated to the Ti(iv) cation via the enolic oxygen, the imino nitrogen and the phenolic oxygen atoms (ONO donor set) in an enol tautomeric form, the metal assuming the distorted octahedral geometry. The structures of pro-ligands H 2 L 3 and H 2 L 5 are also reported. All complexes displayed high hydrolytic stability. In vitro cytotoxicity assays towards human ovarian A2780 and colon HT-29 cancer cell lines revealed the activity dependence on the acylhydrazone substituents, with electron-donating groups on the phenolato units enhancing the solubility and promoting cytotoxicity. The lead compound 5 of this study presents IC 50 values of 2.5 ± 0.2 and 4.2 ± 0.6 μM for ovarian A2780 and colon HT-29 human cancer cells, respectively.
AB - Eight Ti(iv) compounds 1-8, of the type [Ti(L n ) 2 ] where L n is a variously substituted dianionic tridentate acylhydrazone, were synthesized by reacting the appropriate hydrazide with 2-hydroxybenzaldehyde or 2′-hydroxyacetophenone and titanium(iv) tetra(isopropoxide) in a 2 : 2 : 1 molar ratio. The solid-state structures of 1-6 and 7·CH 2 Cl 2 were deduced from the single crystal X-ray diffraction data, which indicated that each L 2− ligand is fully deprotonated and coordinated to the Ti(iv) cation via the enolic oxygen, the imino nitrogen and the phenolic oxygen atoms (ONO donor set) in an enol tautomeric form, the metal assuming the distorted octahedral geometry. The structures of pro-ligands H 2 L 3 and H 2 L 5 are also reported. All complexes displayed high hydrolytic stability. In vitro cytotoxicity assays towards human ovarian A2780 and colon HT-29 cancer cell lines revealed the activity dependence on the acylhydrazone substituents, with electron-donating groups on the phenolato units enhancing the solubility and promoting cytotoxicity. The lead compound 5 of this study presents IC 50 values of 2.5 ± 0.2 and 4.2 ± 0.6 μM for ovarian A2780 and colon HT-29 human cancer cells, respectively.
UR - http://www.scopus.com/inward/record.url?scp=85058732306&partnerID=8YFLogxK
U2 - 10.1039/c8dt03747g
DO - 10.1039/c8dt03747g
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C2 - 30516219
AN - SCOPUS:85058732306
SN - 1477-9226
VL - 48
SP - 304
EP - 314
JO - Dalton Transactions
JF - Dalton Transactions
IS - 1
ER -
