Anti-glioma Activity of Dapsone and Its Enhancement by Synthetic Chemical Modification

Abstract

The sulfone dapsone is an old antibiotic used for the treatment of mycobacterial and protozoal infections. We postulated before that dapsone might possess biological activity exceeding its anti-infectious properties and that it could potentially be repurposed for the treatment of glioma. To test this hypothesis, we treated established and primary cultured glioma cells with dapsone or several dapsone analogues which we previously synthesized (D2-D5) and determined effects on proliferation, anchorage-independent growth and migration. While dapsone and its synthetic analogues D2-D5 displayed only modest anti-proliferative activity, important neoplastic features such as anchorage-independent growth, clonogenic survival and directed migration were significantly inhibited by dapsone treatment. Moreover, dapsone analogues D3, D4 and D5 yielded even enhanced anti-glioma activity against different pro-neoplastic features. Overall these data suggest that dapsone provides activity against glioma which can be further enhanced by molecular modifications. These compounds could potentially serve as a therapeutic adjunct to the treatment of gliomas in a repurposing approach.

Bcl‐2/Bcl‐xL inhibition predominantly synergistically enhances the anti‐neoplastic activity of a low‐dose CUSP9 repurposed drug regime against glioblastoma

“…Scratch assays were performed as previously described (Karpel‐Massler et al, ; Karpel‐Massler, Kast, Siegelin, Dwucet, et al, ). In brief, subconfluent cell layers in 12‐well plates sustained a scratch across the well carried out with a 200‐μl pipette tip.…”

“…Bcl-xL-siRNA I was purchased from Cell Signaling Technology (Signal silence®). Cells were incubated with the formed complexes of Viromer® BLUE (Lipocalyx, Halle, Germany) and the respective siRNA in DMEM with 1.5% FBS for the whole duration of the experiment.2.6 | Real-time PCR and cDNA synthesisRT-PCR was performed as described before using the primers as outlined below: Cell migration/motility assays Scratch assays were performed as previously described(Karpel- Massler et al, 2013;Karpel-Massler, Kast, Siegelin, Dwucet, et al, 2017). In brief, subconfluent cell layers in 12-well plates sustained a scratch across the well carried out with a 200-μl pipette tip.…”

Dapsone as treatment adjunct in ARDS

“…25,26 This use led to the discovery that dapsone ameliorates these dermatoses primarily by inhibiting neutrophil migration along an IL-8 gradient. [27][28][29][30][31][32][33][34][35][36][37] Proof that the characteristic rash caused by erlotinib was mediated by IL-8 in turn led to dapsone use in treating that neutrophilic rash. 29,31,38 In vitro study showed dapsone inhibited neutrophil chemotaxis to both N-formylmethionyl-leucylphenylalanine and to IL-8 via interference with neutrophils' adherence functions.…”

BN‐ and BO‐Doped Inorganic–Organic Hybrid Polymers with Sulfoximine Core Units

“…In light of previous work, [12] sulfoximines 1 and 2 were identified as suitable organic starting materials. Both compounds were N-methylated, thereby confining the reactive anchors ites of the molecules to the free arylic amino and hydroxyl groups.…”

“…The synthetic sequences are shown in Scheme 1. The preparation of 1 startedf rom known diarylsulfide 3, [12] which was imidated and oxidized by adopting ap rotocol reported by Luisi, Bull,and others [13] to give 4 in 62 %y ield. Noteworthy,w ea pplieda queousa mmonia as an itrogen source insteado ft he originally suggested ammonium carbamate.…”