Diiron Complexes Display Potent Antiproliferative Activity and Synergize with Lenalidomide in Diffuse Large B-cell Lymphoma
- 1Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, Pisa, Italy, I-56124
- 2School of Medicine, University of Pisa, Via Roma 55, Pisa, Italy, I-56126
- 3Department of Industrial Chemistry “Toso Montanari, University of Bologna, Via P. Gobetti 85, Bologna, Italy, I-40129
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma (NHL) and remains a clinical challenge in patients with relapsed/refractory disease, despite treatment with lenalidomide- or oxaliplatin-based regimens. Herein, we report on the development of new tailored organometallic complexes evaluated against DLBCL cells as single agents and in combination with lenalidomide. The tailored diiron(I) complexes [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(R’)CHC=NMe(Ind)}]CF3SO3 [R’ = n-pentyl, 2a; R’ = SiMe3, 2b; Cp = h5-C5H5, Ind = 5-(1H-indolyl)] were synthesized in 69-88% yields, and fully characterized by elemental analysis, IR and NMR spectroscopy and, for 2a, by single-crystal X-ray diffraction. The complexes showed adequate aqueous solubility (≈ 10-4 M), balanced hydrophilic/lipophilic character (Log Pow = 0.73 and 0.31) and significant stability in aqueous media, with 90–93% and 73–81% of 2a and 2b, respectively, remaining intact after 72 h in D2O/DMSO-d6 and DMEM-d/DMSO-d6 mixtures at 37 °C. Complexes 2a-b strongly inhibited cell proliferation in SU-DHL10, OCI-LY3 and Toledo DLBCL cell lines after 72 h of exposure; 2a and 2b were substantially more potent than oxaliplatin and lenalidomide, particularly in SU-DHL10 and OCI-LY3 cells, with IC50 values up to 22-fold lower than those of oxaliplatin. Combined treatment with lenalidomide and the diiron complexes, particularly 2a, resulted in strong synergism across almost the entire range of affected fractions (combination index < 1) and dose reduction indices as high as 347 in OCI-LY3 cells. Overall, these findings identify an emerging class of organo-diiron complexes as promising candidates for combination-based therapeutic strategies against DLBCL, warranting further preclinical investigation.
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BibTeX
@misc{benetti2026diiron,
title = {{Diiron Complexes Display Potent Antiproliferative Activity and Synergize with Lenalidomide in Diffuse Large B-cell Lymphoma}},
author = {Sara Benetti and Marta Banchi and Lorenzo Biancalana and Alessio Isolani and Stefano Zacchini and Guido Bocci and Fabio Marchetti and FABIO MARCHETTI},
howpublished = {ChemRxiv},
year = {2026},
month = aug,
doi = {10.26434/chemrxiv.15008129/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008129/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Diiron Complexes Display Potent Antiproliferative Activity and Synergize with Lenalidomide in Diffuse Large B-cell Lymphoma
AU - Sara Benetti
AU - Marta Banchi
AU - Lorenzo Biancalana
AU - Alessio Isolani
AU - Stefano Zacchini
AU - Guido Bocci
AU - Fabio Marchetti
AU - FABIO MARCHETTI
PY - 2026
DA - 2026/08/31
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008129/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008129/v1
AB - Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma (NHL) and remains a clinical challenge in patients with relapsed/refractory disease, despite treatment with lenalidomide- or oxaliplatin-based regimens. Herein, we report on the development of new tailored organometallic complexes evaluated against DLBCL cells as single agents and in combination with lenalidomide. The tailored diiron(I) complexes [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(R’)CHC=NMe(Ind)}]CF3SO3 [R’ = n-pentyl, 2a; R’ = SiMe3, 2b; Cp = h5-C5H5, Ind = 5-(1H-indolyl)] were synthesized in 69-88% yields, and fully characterized by elemental analysis, IR and NMR spectroscopy and, for 2a, by single-crystal X-ray diffraction. The complexes showed adequate aqueous solubility (≈ 10-4 M), balanced hydrophilic/lipophilic character (Log Pow = 0.73 and 0.31) and significant stability in aqueous media, with 90–93% and 73–81% of 2a and 2b, respectively, remaining intact after 72 h in D2O/DMSO-d6 and DMEM-d/DMSO-d6 mixtures at 37 °C. Complexes 2a-b strongly inhibited cell proliferation in SU-DHL10, OCI-LY3 and Toledo DLBCL cell lines after 72 h of exposure; 2a and 2b were substantially more potent than oxaliplatin and lenalidomide, particularly in SU-DHL10 and OCI-LY3 cells, with IC50 values up to 22-fold lower than those of oxaliplatin. Combined treatment with lenalidomide and the diiron complexes, particularly 2a, resulted in strong synergism across almost the entire range of affected fractions (combination index < 1) and dose reduction indices as high as 347 in OCI-LY3 cells. Overall, these findings identify an emerging class of organo-diiron complexes as promising candidates for combination-based therapeutic strategies against DLBCL, warranting further preclinical investigation.
ER -