BODIPY-Appended Pt(II) Complexes with High Toxicities and Anti-chemoresistance Performances in a Cisplatin Resistant In Vivo Model.

Chong, H; Tan, C; Fang, S; Chen, X; Tao, Q; Yuan, X; Li, J; Zhai, C; Fei, C; Yang, D; Fan, H; Shao, H; Qin, A; Wang, G; Shi, Z; Z'hang, T; Yao, H; Li, H; Wang, C

BODIPY-Appended Pt(II) Complexes with High Toxicities and Anti-chemoresistance Performances in a Cisplatin Resistant In Vivo Model.

Chong, H Tan, C Fang, S Chen, X Tao, Q Yuan, X Li, J Zhai, C Fei, C Yang, D Fan, H Shao, H Qin, A Wang, G

Shi, Z Z'hang, T Yao, H Li, H Wang, C

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Publisher:: AMER CHEMICAL SOC
Publication Type:: Journal Article
Citation:: Inorg Chem, 2021, 60, (13), pp. 10047-10055
Issue Date:: 2021-07-05

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Field	Value	Language
dc.contributor.author	Chong, H
dc.contributor.author	Tan, C
dc.contributor.author	Fang, S
dc.contributor.author	Chen, X
dc.contributor.author	Tao, Q
dc.contributor.author	Yuan, X
dc.contributor.author	Li, J
dc.contributor.author	Zhai, C
dc.contributor.author	Fei, C
dc.contributor.author	Yang, D
dc.contributor.author	Fan, H
dc.contributor.author	Shao, H
dc.contributor.author	Qin, A
dc.contributor.author	Wang, G https://orcid.org/0000-0003-4295-8578
dc.contributor.author	Shi, Z
dc.contributor.author	Z'hang, T
dc.contributor.author	Yao, H
dc.contributor.author	Li, H
dc.contributor.author	Wang, C
dc.date.accessioned	2022-01-17T03:55:37Z
dc.date.available	2022-01-17T03:55:37Z
dc.date.issued	2021-07-05
dc.identifier.citation	Inorg Chem, 2021, 60, (13), pp. 10047-10055
dc.identifier.issn	0020-1669
dc.identifier.issn	1520-510X
dc.identifier.uri	http://hdl.handle.net/10453/153208
dc.description.abstract	Two novel fluorophore (BODIPY)-bearing complexes, pyriplatin (mCBP) and pyrimidine-chelated cisplatin (dCBP), were synthesized and characterized. The additional BODIPY-pyridine/pyridimine motifs of the two Pt(II) complexes resulted in stronger interactions with DNA in comparison with those of cisplatin. mCBP and cisplatin caused relative decreases in life span and body length in a cisplatin resistant in vivo model, N2 (wild-type) Caenorhabditis elegans. In contrast, dCBP resulted in a dramatic reduction in the two physiological parameters in N2 C. elegans, indicating high toxicity and sensitivity. The resistance factors (RF) of cisplatin, mCBP, and dCBP were determined to be 2.46, 1.04, and 0.91, respectively. The increasing RF folds for mCBP and dCBP against cisplatin were 2.36 and 2.70, respectively. This suggested they were featured with improved anti-chemoresistance capabilities. It is noteworthy that dCBP showed lowest lethal concentration (LC50) values of 0.56 and 0.61 mM in cisplatin resistant and sensitive in vivo models, respectively. Upregulation of several evolutionary conservation genes that regulate cisplatin chemoresistance through cisplatin effluxing, the DNA damage response, the unfolded protein response, and detoxification (asna-1, parp-1, enpl-1, and skn-1) was observed upon exposure to cisplatin but not to mCBP and dCBP. This could explain the improved anti-chemoresistance performances of synthesized Pt(II) complexes.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER CHEMICAL SOC
dc.relation.ispartof	Inorg Chem
dc.relation.isbasedon	10.1021/acs.inorgchem.1c01471
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0302 Inorganic Chemistry, 0306 Physical Chemistry (incl. Structural), 0399 Other Chemical Sciences
dc.subject.classification	Inorganic & Nuclear Chemistry
dc.subject.mesh	Animals
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Boron Compounds
dc.subject.mesh	Caenorhabditis elegans
dc.subject.mesh	Cell Survival
dc.subject.mesh	Cisplatin
dc.subject.mesh	Dose-Response Relationship, Drug
dc.subject.mesh	Mice
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Organoplatinum Compounds
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Caenorhabditis elegans
dc.subject.mesh	Boron Compounds
dc.subject.mesh	Cisplatin
dc.subject.mesh	Organoplatinum Compounds
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Cell Survival
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Dose-Response Relationship, Drug
dc.title	BODIPY-Appended Pt(II) Complexes with High Toxicities and Anti-chemoresistance Performances in a Cisplatin Resistant In Vivo Model.
dc.type	Journal Article
utslib.citation.volume	60
utslib.location.activity	United States
utslib.for	0302 Inorganic Chemistry
utslib.for	0306 Physical Chemistry (incl. Structural)
utslib.for	0399 Other Chemical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
utslib.copyright.status	closed_access	*
dc.date.updated	2022-01-17T03:55:35Z
pubs.issue	13
pubs.publication-status	Published
pubs.volume	60
utslib.citation.issue	13

Abstract:

Two novel fluorophore (BODIPY)-bearing complexes, pyriplatin (mCBP) and pyrimidine-chelated cisplatin (dCBP), were synthesized and characterized. The additional BODIPY-pyridine/pyridimine motifs of the two Pt(II) complexes resulted in stronger interactions with DNA in comparison with those of cisplatin. mCBP and cisplatin caused relative decreases in life span and body length in a cisplatin resistant in vivo model, N2 (wild-type) Caenorhabditis elegans. In contrast, dCBP resulted in a dramatic reduction in the two physiological parameters in N2 C. elegans, indicating high toxicity and sensitivity. The resistance factors (RF) of cisplatin, mCBP, and dCBP were determined to be 2.46, 1.04, and 0.91, respectively. The increasing RF folds for mCBP and dCBP against cisplatin were 2.36 and 2.70, respectively. This suggested they were featured with improved anti-chemoresistance capabilities. It is noteworthy that dCBP showed lowest lethal concentration (LC50) values of 0.56 and 0.61 mM in cisplatin resistant and sensitive in vivo models, respectively. Upregulation of several evolutionary conservation genes that regulate cisplatin chemoresistance through cisplatin effluxing, the DNA damage response, the unfolded protein response, and detoxification (asna-1, parp-1, enpl-1, and skn-1) was observed upon exposure to cisplatin but not to mCBP and dCBP. This could explain the improved anti-chemoresistance performances of synthesized Pt(II) complexes.

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http://hdl.handle.net/10453/153208