TY - JOUR
T1 - New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives
T2 - A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics
AU - Banti, Christina N.
AU - Papatriantafyllopoulou, Constantina
AU - Papachristodoulou, Christina
AU - Hatzidimitriou, Antonios G.
AU - Hadjikakou, Sotiris K.
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/3/23
Y1 - 2023/3/23
N2 - {[Ag8(Mef)8(μ2-S,O-DMSO)2(μ2-O-DMSO)2(O-DMSO)8]·2(H2O)} (1), [Ag(Mef)(tpP)2] (2), [Ag(Mef)(tpAs)3] (3), and {2 [Ag(Mef)(tpSb)3] (DMSO)} (4) were obtained by the conjugation of mefenamic acid (MefH), a nonsteroidal anti-inflammatory drug (NSAID), with a mitochondriotropic derivative of pnictogen tpE (tp = triphenyl group; E = P, As, and Sb) through silver(I). Their hydrophilicity was adjusted by their dispersion into sodium lauryl sulfate (SLS), forming SLS@1-4. 1-4 and SLS@1-4 were characterized by their spectral data and X-ray crystallography. They inhibit the proliferation of human breast adenocarcinoma cells MCF-7 (hormone-dependent (HD)) and MDA-MB-231 (hormone-independent (HI)). X-ray fluorescence reveals the Ag cellular uptake. The in vitro and in vivo nongenotoxicity was confirmed with micronucleus (MN), Artemia salina, and Allium cepa assays. Their mechanism of action was studied by cell morphology, DNA fragmentation, acridine orange/ethidium bromide (AO/EB) staining, cell cycle arrest, mitochondrial membrane permeabilization tests, DNA binding affinity, and LOX inhibitory activity and was rationalized by regression analysis.
AB - {[Ag8(Mef)8(μ2-S,O-DMSO)2(μ2-O-DMSO)2(O-DMSO)8]·2(H2O)} (1), [Ag(Mef)(tpP)2] (2), [Ag(Mef)(tpAs)3] (3), and {2 [Ag(Mef)(tpSb)3] (DMSO)} (4) were obtained by the conjugation of mefenamic acid (MefH), a nonsteroidal anti-inflammatory drug (NSAID), with a mitochondriotropic derivative of pnictogen tpE (tp = triphenyl group; E = P, As, and Sb) through silver(I). Their hydrophilicity was adjusted by their dispersion into sodium lauryl sulfate (SLS), forming SLS@1-4. 1-4 and SLS@1-4 were characterized by their spectral data and X-ray crystallography. They inhibit the proliferation of human breast adenocarcinoma cells MCF-7 (hormone-dependent (HD)) and MDA-MB-231 (hormone-independent (HI)). X-ray fluorescence reveals the Ag cellular uptake. The in vitro and in vivo nongenotoxicity was confirmed with micronucleus (MN), Artemia salina, and Allium cepa assays. Their mechanism of action was studied by cell morphology, DNA fragmentation, acridine orange/ethidium bromide (AO/EB) staining, cell cycle arrest, mitochondrial membrane permeabilization tests, DNA binding affinity, and LOX inhibitory activity and was rationalized by regression analysis.
UR - https://www.scopus.com/pages/publications/85147948975
U2 - 10.1021/acs.jmedchem.2c02126
DO - 10.1021/acs.jmedchem.2c02126
M3 - Article
SN - 0022-2623
VL - 66
SP - 4131
EP - 4149
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 6
ER -
