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Synthesis and New Cytotoxicity Screening Approach of Novel Dirhodium Complexes
Author(s) -
Saulino Emily N.,
Dunham Stephen,
Thévenin Anastasia
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r4325
Subject(s) - chemistry , cytotoxicity , cisplatin , hela , benzylamine , reagent , reactivity (psychology) , combinatorial chemistry , medicinal chemistry , organic chemistry , in vitro , biochemistry , medicine , alternative medicine , surgery , chemotherapy , pathology
Transition metal–based chemotherapeutics have been used to treat a variety of cancers since the 1960s with cisplatin being the most prominent of these drugs used in a clinical setting. Many cancers become chemoresistant to cisplatin, so there is currently a need to synthesize and explore the anticancer abilities of other transition metal complexes. Rhodium, one of the six platinum–group metals, demonstrates cytotoxic effects in cancer cells in the form of dirhodium tetraacetate (Rh 2 A4). However, Rh 2 A4 is known to be less cytotoxic than cisplatin in HeLa cervical cancer cells. This research aims to modify Rh 2 A4 to increase its cytotoxicity to that of cisplatin. One of the acetate ligands of Rh 2 A4 was selectively replaced with 6‐maleimidohexanoic acid (M) to form a dirhodium triacetate maleimide (Rh 2 A3M) complex. Maleimides are known to readily react with alkylamines (R‐NH 2 ) under basic conditions to produce amine conjugates. Alkylamines were chosen because of this reactivity and because their presence in a variety of metabolic and physiological processes may aid in the uptake of the dirhodum complex in cancer cells. The Rh 2 A3M complex was successfully reacted with four alkylamines: benzylamine, cyclohexylamine, ethanolamine, and glucosamine. This reaction was done in a 1:10 molar ratio in a phosphate buffer of pH 7.25 at room temperature for 72 hours to form subsequent Rh 2 A3M‐NH‐R complexes. The crude reaction mixture was then purified by preparative HPLC and characterized via 1 H 1D NMR. A new screening method was developed using MTT reagent to compare the cellular viability of HeLa cervical cancer cells treated with the four crude reaction mixtures and the four HPLC purified Rh 2 A3M‐NH‐R complexes. Each pure complex had a similar percent cellular viability to its corresponding crude reaction mixture. This procedure will allow for future screens of many Rh 2 A3M + R‐NH 2 crude reaction mixtures to indicate cytotoxicity of Rh 2 A3M‐NH‐R products without the need for the purification and characterization steps. Out of the four pure complexes, Rh 2 A3M‐cyclohexylamine was found to be the most cytotoxic at ~20 μM, suggesting it is comparable in cytotoxicity to cisplatin. Current work is focused on the determination of the IC 50 value for this complex to definitively compare its cytotoxicity to cisplatin.