New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics

Christina N. Banti; Constantina Papatriantafyllopoulou; Christina Papachristodoulou; Antonios G. Hatzidimitriou; Sotiris K. Hadjikakou

doi:10.1021/acs.jmedchem.2c02126

New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics

Christina N. Banti
, Constantina Papatriantafyllopoulou
, Christina Papachristodoulou
, Antonios G. Hatzidimitriou
, Sotiris K. Hadjikakou

Cellular & Molecular Medicine

University of Ioannina
Aristotle University of Thessaloniki

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

21 Citations (Scopus)

Abstract

{[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.

Original language	English
Pages (from-to)	4131-4149
Number of pages	19
Journal	Journal of Medicinal Chemistry
Volume	66
Issue number	6
DOIs	https://doi.org/10.1021/acs.jmedchem.2c02126
Publication status	Published - 23 Mar 2023

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10.1021/acs.jmedchem.2c02126

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Banti, C. N., Papatriantafyllopoulou, C., Papachristodoulou, C., Hatzidimitriou, A. G., & Hadjikakou, S. K. (2023). New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics. Journal of Medicinal Chemistry, 66(6), 4131-4149. https://doi.org/10.1021/acs.jmedchem.2c02126

@article{8be2476d492d4b638bcebfd34d4c9290,

title = "New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics",

abstract = "\{[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.",

author = "Banti, \{Christina N.\} and Constantina Papatriantafyllopoulou and Christina Papachristodoulou and Hatzidimitriou, \{Antonios G.\} and Hadjikakou, \{Sotiris K.\}",

note = "Publisher Copyright: {\textcopyright} 2023 American Chemical Society.",

year = "2023",

month = mar,

day = "23",

doi = "10.1021/acs.jmedchem.2c02126",

language = "English",

volume = "66",

pages = "4131--4149",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

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number = "6",

}

Banti, CN, Papatriantafyllopoulou, C, Papachristodoulou, C, Hatzidimitriou, AG & Hadjikakou, SK 2023, 'New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics', Journal of Medicinal Chemistry, vol. 66, no. 6, pp. 4131-4149. https://doi.org/10.1021/acs.jmedchem.2c02126

New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics. / Banti, Christina N.; Papatriantafyllopoulou, Constantina; Papachristodoulou, Christina et al.
In: Journal of Medicinal Chemistry, Vol. 66, No. 6, 23.03.2023, p. 4131-4149.

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

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.

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 -

New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics

Abstract

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