Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates
A new series of cytotoxic platinum(IV) complexes (<b>1</b>–<b>8</b>) incorporating halogenated phenylacetic acid derivatives (4-chlorophenylacetic acid, 4-fluorophenylacetic acid, 4-bromophenylacetic acid and 4-iodophenylacetic acid) were synthesised and characterised using s...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/20/7120 |
| _version_ | 1797470779562000384 |
|---|---|
| author | Angelico D. Aputen Maria George Elias Jayne Gilbert Jennette A. Sakoff Christopher P. Gordon Kieran F. Scott Janice R. Aldrich-Wright |
| author_facet | Angelico D. Aputen Maria George Elias Jayne Gilbert Jennette A. Sakoff Christopher P. Gordon Kieran F. Scott Janice R. Aldrich-Wright |
| author_sort | Angelico D. Aputen |
| collection | DOAJ |
| description | A new series of cytotoxic platinum(IV) complexes (<b>1</b>–<b>8</b>) incorporating halogenated phenylacetic acid derivatives (4-chlorophenylacetic acid, 4-fluorophenylacetic acid, 4-bromophenylacetic acid and 4-iodophenylacetic acid) were synthesised and characterised using spectroscopic and spectrometric techniques. Complexes <b>1</b>–<b>8</b> were assessed on a panel of cell lines including HT29 colon, U87 glioblastoma, MCF-7 breast, A2780 ovarian, H460 lung, A431 skin, Du145 prostate, BE2-C neuroblastoma, SJ-G2 glioblastoma, MIA pancreas, the ADDP-resistant ovarian variant, and the non-tumour-derived MCF10A breast line. The in vitro cytotoxicity results confirmed the superior biological activity of the studied complexes, especially those containing 4-fluorophenylacetic acid and 4-bromophenylacetic acid ligands, namely <b>4</b> and <b>6</b>, eliciting an average GI<sub>50</sub> value of 20 nM over the range of cell lines tested. In the Du145 prostate cell line, <b>4</b> exhibited the highest degree of potency amongst the derivatives, displaying a GI<sub>50</sub> value of 0.7 nM, which makes it 1700-fold more potent than cisplatin (1200 nM) and nearly 7-fold more potent than our lead complex, <b>56ME<i>SS</i></b> (4.6 nM) in this cell line. Notably, in the ADDP-resistant ovarian variant cell line, <b>4</b> (6 nM) was found to be almost 4700-fold more potent than cisplatin. Reduction reaction experiments were also undertaken, along with studies aimed at determining the complexes’ solubility, stability, lipophilicity, and reactive oxygen species production. |
| first_indexed | 2024-03-09T19:41:46Z |
| format | Article |
| id | doaj.art-c9af94e27190424db7547603cd8e96f5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:41:46Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c9af94e27190424db7547603cd8e96f52023-11-24T01:37:49ZengMDPI AGMolecules1420-30492022-10-012720712010.3390/molecules27207120Bioactive Platinum(IV) Complexes Incorporating Halogenated PhenylacetatesAngelico D. Aputen0Maria George Elias1Jayne Gilbert2Jennette A. Sakoff3Christopher P. Gordon4Kieran F. Scott5Janice R. Aldrich-Wright6School of Science, Western Sydney University, Locked Bag 1797, Sydney, NSW 2751, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797, Sydney, NSW 2751, AustraliaCalvary Mater Newcastle Hospital, Newcastle, NSW 2298, AustraliaCalvary Mater Newcastle Hospital, Newcastle, NSW 2298, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797, Sydney, NSW 2751, AustraliaIngham Institute, Sydney, NSW 2170, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797, Sydney, NSW 2751, AustraliaA new series of cytotoxic platinum(IV) complexes (<b>1</b>–<b>8</b>) incorporating halogenated phenylacetic acid derivatives (4-chlorophenylacetic acid, 4-fluorophenylacetic acid, 4-bromophenylacetic acid and 4-iodophenylacetic acid) were synthesised and characterised using spectroscopic and spectrometric techniques. Complexes <b>1</b>–<b>8</b> were assessed on a panel of cell lines including HT29 colon, U87 glioblastoma, MCF-7 breast, A2780 ovarian, H460 lung, A431 skin, Du145 prostate, BE2-C neuroblastoma, SJ-G2 glioblastoma, MIA pancreas, the ADDP-resistant ovarian variant, and the non-tumour-derived MCF10A breast line. The in vitro cytotoxicity results confirmed the superior biological activity of the studied complexes, especially those containing 4-fluorophenylacetic acid and 4-bromophenylacetic acid ligands, namely <b>4</b> and <b>6</b>, eliciting an average GI<sub>50</sub> value of 20 nM over the range of cell lines tested. In the Du145 prostate cell line, <b>4</b> exhibited the highest degree of potency amongst the derivatives, displaying a GI<sub>50</sub> value of 0.7 nM, which makes it 1700-fold more potent than cisplatin (1200 nM) and nearly 7-fold more potent than our lead complex, <b>56ME<i>SS</i></b> (4.6 nM) in this cell line. Notably, in the ADDP-resistant ovarian variant cell line, <b>4</b> (6 nM) was found to be almost 4700-fold more potent than cisplatin. Reduction reaction experiments were also undertaken, along with studies aimed at determining the complexes’ solubility, stability, lipophilicity, and reactive oxygen species production.https://www.mdpi.com/1420-3049/27/20/7120chemotherapycisplatin<b>PHEN<i>SS</i></b><b>56ME<i>SS</i></b>platinum(II)platinum(IV) |
| spellingShingle | Angelico D. Aputen Maria George Elias Jayne Gilbert Jennette A. Sakoff Christopher P. Gordon Kieran F. Scott Janice R. Aldrich-Wright Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates Molecules chemotherapy cisplatin <b>PHEN<i>SS</i></b> <b>56ME<i>SS</i></b> platinum(II) platinum(IV) |
| title | Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates |
| title_full | Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates |
| title_fullStr | Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates |
| title_full_unstemmed | Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates |
| title_short | Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates |
| title_sort | bioactive platinum iv complexes incorporating halogenated phenylacetates |
| topic | chemotherapy cisplatin <b>PHEN<i>SS</i></b> <b>56ME<i>SS</i></b> platinum(II) platinum(IV) |
| url | https://www.mdpi.com/1420-3049/27/20/7120 |
| work_keys_str_mv | AT angelicodaputen bioactiveplatinumivcomplexesincorporatinghalogenatedphenylacetates AT mariageorgeelias bioactiveplatinumivcomplexesincorporatinghalogenatedphenylacetates AT jaynegilbert bioactiveplatinumivcomplexesincorporatinghalogenatedphenylacetates AT jennetteasakoff bioactiveplatinumivcomplexesincorporatinghalogenatedphenylacetates AT christopherpgordon bioactiveplatinumivcomplexesincorporatinghalogenatedphenylacetates AT kieranfscott bioactiveplatinumivcomplexesincorporatinghalogenatedphenylacetates AT janiceraldrichwright bioactiveplatinumivcomplexesincorporatinghalogenatedphenylacetates |