Synthesis schema of cis, cis, trans-[Pt(NH₃)₂Cl₂(PBA)₂] [Compound B] Addition of 4-phenylbutanoic anhydride reagent to cis, cis, trans-[Pt(NH₃)₂Cl₂(OH)₂] results in the substitution of PBA HDAC inhibitor ligands for the hydroxides on cis, cis, trans-[Pt(NH₃)₂Cl₂(OH)₂]. See Supplementary Fig. S1 and S2 for NMR and HR-ESI-MS validation

Compound B reduces ovarian cancer metastasis comparably to cisplatin.Images show ovarian cancer cells labeled with DiI membrane stain visible in the red fluorescent channel. A.-D. Representative images of microinjected zebrafish embryos (A. brightfield cranial view showing yolk sac injection site (black arrow); B. brightfield caudal view; C. red channel fluorescent cranial view showing yolk sac injection site with cancer cells (white arrow); D. red channel fluorescent caudal view showing metastasized A2780cis cells (white arrow head), E.-J. Representative images of control and experimental treatment zebrafish (E., E3 media control; F., 0.9% NaCl cisplatin control; G., 0.3% DMSO compound B control; H., 0.3 µM compound B; I., 0.6 µM compound B; J., 2.0 µM cisplatin). K. Comparison of E3 media (Con), 0.9% NaCl, and 0.3% DMSO controls. L. Comparison of E3 control (Con) with three platinum complex treatments: 0.3 µM compound B [B(0.3)], 0.6 µM compound B [B(0.6)], 2.0 µM cisplatin [C(2.0)]. CTCF = corrected total cell fluorescence; p < 0.05, “*” = 0.05; N = 5–15

Cisplatin and compound B treatment caused increased general tissue cell apoptosis in zebrafish AB embryos A.-F. Representative images of control and experimental compound (A., 0.3% DMSO; B., 0.3 µM compound B; C., 0.9% NaCl; D., 2 µM cisplatin; E., E3 media; F., 10 nM CCCP) treated zebrafish embryos). G. Graph of average number of apoptotic cells observed for control and experimental compound treated zebrafish embryos. Arrow in A. indicates caspase-3 positive cell. Key: Con = E3 egg water media control; C = cisplatin; C-V = cisplatin 0.9% NaCl vehicle control; B = compound B; B-V = 0.3% DMSO compound B vehicle; CCCP = 10 nM carbonyl cyanide m-chlorophenyl hydrazine positive control; p < 0.05, “*” = 0.05, “****” = 0.0001

Cisplatin treatment decreased neuromast hair cell numbers more than compound B in brn3c(pouf4f3):eGFP zebrafish A.-F. Representative images of control and experimental compound (A., 0.3% DMSO; B., 0.3 µM compound B; C., 0.9% NaCl; D., 2 µM cisplatin; E., E3 media; F., 100 µM cisplatin) treated brn3c (pouf4f3):eGFP zebrafish embryos. G. Graph of average number of neuromast hair cells counted for control and experimental compound treated zebrafish embryos. Arrow in A. indicates neuromast expressing GFP reporter. Key: Con = E3 egg water media control; C = cisplatin; C-V = cisplatin 0.9% NaCl vehicle control; B = compound B; B-V = 0.3% DMSO compound B vehicle control; ↑C = 100 µM cisplatin overdose used as a positive control; p < 0.05, “*” = 0.05, “**” = 0.01, “****” = 0.0001, ns = non-significant

Compound B does not cause decreased glomerular filtration in AB zebrafish A.-I. Representative images of control and experimental compound treated AB zebrafish embryos showing red fluorescent dye distribution at 1, 5, and 24 hpi (A., dextran control-1 hpi; B., 2 µM cisplatin-1 hpi; C., 0.6 µM compound B-1 hpi; D., dextran control-5 hpi; E., 2 µM cisplatin-5 hpi; F., 0.6 µM compound B-5 hpi; G., dextran control-24 hpi; H., 2 µM cisplatin-24 hpi; I., 0.6 µM compound B-24 hpi; ), J. Examples of region-of-interest (ROI) analysis (top panel: representative polygon for ROI measurement of fluorescence; bottom panel: representative polygon for ROI measurement of background), K., Graph of fluorescent intensity for control and experimental compound treated zebrafish embryos at 1, 5, and 24 hpi. Key: CTCF (RFU) = corrected total cell fluorescence in relative fluorescence units; white columns = dextran control; light gray columns = 2 µM cisplatin; dark gray columns = 0.6 µM compound B; p < 0.05, “*” = 0.05, “**” = 0.01, “***” = 0.001; N = 5–10