TY - JOUR
T1 - Aryl bismuth phosphinates [BiAr2(O(O)PRR′)]
T2 - structure-activity relationships for antibacterial activity and cytotoxicity
AU - Herdman, Megan E.
AU - Werrett, Melissa V.
AU - Andrews, Philip C.
N1 - Funding Information:
The authors would like to thank The National Health and Medical Research Council (APP1139844) for financial support and Monash University. The authors acknowledge the use of the facilities within the Monash X-ray Platform and the Australian Synchrotron. The authors also thank Dr Craig Forsyth (Monash) for assistance with X-ray crystallography, and Dr Rebekah Duffin (Monash) for the synthesis of Bi(o-MeOPh)3. We also wish to thank Professor Benjamin Howden (Doherty Institute) for the MRSA and VRE strains, and Dr Toby Bell (Monash) for the Cos-7 cells.
Funding Information:
The authors would like to thank The National Health and Medical Research Council (APP1139844) for financial support and Monash University. The authors acknowledge the use of the facilities within the Monash X-ray Platform and the Australian Synchrotron. The authors also thank Dr Craig Forsyth (Monash) for assistance with X-ray crystallography, and Dr Rebekah Duffin (Monash) for the synthesis of Bi(o-MeOPh). We also wish to thank Professor Benjamin Howden (Doherty Institute) for the MRSA and VRE strains, and Dr Toby Bell (Monash) for the Cos-7 cells. 3
Publisher Copyright:
© 2022 The Royal Society of Chemistry.
PY - 2022/6/28
Y1 - 2022/6/28
N2 - To study and evaluate the structure-activity relationships in di-aryl bismuth phosphinates on antibacterial activity and cytotoxicity a series of complexes containing ortho-methoxyphenyl, meta-methoxyphenyl, meta-tolyl and para-tolyl aryl groups; [Bi(o-MeOPh)2(O(O)P(H)Ph)]n1, [Bi(o-MeOPh)2(O(O)PPh2)]n2, [Bi(o-MeOPh)2(O(O)P(p-MeOPh)2)]n3, [Bi(m-MeOPh)2(O(O)P(H)Ph)]n4, [Bi(m-MeOPh)2(O(O)PPh2)]n5, [Bi(m-MeOPh)2(O(O)P(p-MeOPh)2)]n6, [Bi(m-tol)2(O(O)P(H)Ph)]n7, [Bi(m-tol)2(O(O)PPh2)]n8, [Bi(m-tol)2(O(O)P(p-MeOPh)2)]n9, [Bi(p-tol)2(O(O)P(H)Ph)]n10, [Bi(p-tol)2(O(O)PPh2)]n11 and [Bi(p-tol)2(O(O)P(p-MeOPh)2)]n12, were synthesised and characterised. Complexes 4, 7, 8, 10 and 11 were structurally authenticated by X-ray crystallography. Evaluation of their antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) showed that the bismuth bound aryl group has a profound influence on activity, with the o-MeOPh complexes 1-3 showing very little activity while the m-MeOPh complexes have the greatest activity towards MRSA and VRE in the range of 0.63 to 1.25 μM. Viability studies with Cos-7 cells showed that the di-aryl bismuth complexes 1-12 are less cytotoxic than their di-phenyl bismuth analogues, with a general trend of toxicity observed as p-tolyl > m-tolyl > m-methoxyphenyl > o-methoxyphenyl. The large difference in Cos-7 viability for complexes 1 (IC50 > 80 μM) and 4 (IC50 14.0 μM) was further investigated through bismuth uptake studies, where there was no obvious difference in Cos-7 bismuth uptake at 5 μM. This suggests that the bismuth-bound aryl group has a significant impact on biological activity, which is then further mediated by other ligands.
AB - To study and evaluate the structure-activity relationships in di-aryl bismuth phosphinates on antibacterial activity and cytotoxicity a series of complexes containing ortho-methoxyphenyl, meta-methoxyphenyl, meta-tolyl and para-tolyl aryl groups; [Bi(o-MeOPh)2(O(O)P(H)Ph)]n1, [Bi(o-MeOPh)2(O(O)PPh2)]n2, [Bi(o-MeOPh)2(O(O)P(p-MeOPh)2)]n3, [Bi(m-MeOPh)2(O(O)P(H)Ph)]n4, [Bi(m-MeOPh)2(O(O)PPh2)]n5, [Bi(m-MeOPh)2(O(O)P(p-MeOPh)2)]n6, [Bi(m-tol)2(O(O)P(H)Ph)]n7, [Bi(m-tol)2(O(O)PPh2)]n8, [Bi(m-tol)2(O(O)P(p-MeOPh)2)]n9, [Bi(p-tol)2(O(O)P(H)Ph)]n10, [Bi(p-tol)2(O(O)PPh2)]n11 and [Bi(p-tol)2(O(O)P(p-MeOPh)2)]n12, were synthesised and characterised. Complexes 4, 7, 8, 10 and 11 were structurally authenticated by X-ray crystallography. Evaluation of their antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) showed that the bismuth bound aryl group has a profound influence on activity, with the o-MeOPh complexes 1-3 showing very little activity while the m-MeOPh complexes have the greatest activity towards MRSA and VRE in the range of 0.63 to 1.25 μM. Viability studies with Cos-7 cells showed that the di-aryl bismuth complexes 1-12 are less cytotoxic than their di-phenyl bismuth analogues, with a general trend of toxicity observed as p-tolyl > m-tolyl > m-methoxyphenyl > o-methoxyphenyl. The large difference in Cos-7 viability for complexes 1 (IC50 > 80 μM) and 4 (IC50 14.0 μM) was further investigated through bismuth uptake studies, where there was no obvious difference in Cos-7 bismuth uptake at 5 μM. This suggests that the bismuth-bound aryl group has a significant impact on biological activity, which is then further mediated by other ligands.
UR - http://www.scopus.com/inward/record.url?scp=85131969530&partnerID=8YFLogxK
U2 - 10.1039/d2dt00346e
DO - 10.1039/d2dt00346e
M3 - Article
C2 - 35670553
AN - SCOPUS:85131969530
SN - 1477-9226
VL - 51
SP - 9323
EP - 9335
JO - Dalton Transactions
JF - Dalton Transactions
IS - 24
ER -