Cytotoxic homoleptic Ti(iv) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity

Rajesh Manne; Maya Miller; Andrew Duthie; M. Fátima C. Guedes Da Silva; Edit Y. Tshuva; Tushar S. Basu Baul

doi:10.1039/c8dt03747g

Cytotoxic homoleptic Ti(iv) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity

Rajesh Manne, Maya Miller, Andrew Duthie, M. Fátima C. Guedes Da Silva^*, Edit Y. Tshuva, Tushar S. Basu Baul

^*Corresponding author for this work

Institute of Chemistry

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

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.

Original language	American English
Pages (from-to)	304-314
Number of pages	11
Journal	Dalton Transactions
Volume	48
Issue number	1
DOIs	https://doi.org/10.1039/c8dt03747g
State	Published - 2019

Bibliographical note

Funding Information:
Funding was received from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 681243). Additional financial support from the University Grants Commission, New Delhi (Grant No. Sanction No. 42-396/2013 (SR), 2013, TSBB) and the University Grants Commission, New Delhi, India through SAP-CAS, Phase-I (Grant No. F 540/21/CAS/2013 (SAP-I)) is gratefully acknowledged. TSBB and RM acknowledge DST-PURSE for the diffractometer facility. Deakin University’s Advanced Characterisation Facility is acknowledged for use of the Bruker Avance III spectrometer.

Publisher Copyright:
© The Royal Society of Chemistry.

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@article{adbba49d91744a389ec89c82fa43dc65,

title = "Cytotoxic homoleptic Ti(iv) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity",

abstract = " 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.",

author = "Rajesh Manne and Maya Miller and Andrew Duthie and {Guedes Da Silva}, {M. F{\'a}tima C.} and Tshuva, {Edit Y.} and {Basu Baul}, {Tushar S.}",

note = "Funding Information: Funding was received from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement 681243). Additional financial support from the University Grants Commission, New Delhi (Grant No. Sanction No. 42-396/2013 (SR), 2013, TSBB) and the University Grants Commission, New Delhi, India through SAP-CAS, Phase-I (Grant No. F 540/21/CAS/2013 (SAP-I)) is gratefully acknowledged. TSBB and RM acknowledge DST-PURSE for the diffractometer facility. Deakin University{\textquoteright}s Advanced Characterisation Facility is acknowledged for use of the Bruker Avance III spectrometer. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2019",

doi = "10.1039/c8dt03747g",

language = "American English",

volume = "48",

pages = "304--314",

journal = "Dalton Transactions",

issn = "1477-9226",

publisher = "Royal Society of Chemistry",

number = "1",

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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 - Funding Information: Funding was received from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 681243). Additional financial support from the University Grants Commission, New Delhi (Grant No. Sanction No. 42-396/2013 (SR), 2013, TSBB) and the University Grants Commission, New Delhi, India through SAP-CAS, Phase-I (Grant No. F 540/21/CAS/2013 (SAP-I)) is gratefully acknowledged. TSBB and RM acknowledge DST-PURSE for the diffractometer facility. Deakin University’s Advanced Characterisation Facility is acknowledged for use of the Bruker Avance III spectrometer. 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

M3 - Article

C2 - 30516219

AN - SCOPUS:85058732306

SN - 1477-9226

VL - 48

SP - 304

EP - 314

JO - Dalton Transactions

JF - Dalton Transactions

IS - 1

ER -

Cytotoxic homoleptic Ti(iv) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity

Abstract

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