A greener, economical, and efficient methodology for the Michael addition of thiols to N-aryl maleimides has been developed.

Glioblastoma multiforme (GBM) is a dreadful cancer characterised by poor prognosis, low survival rate and difficult clinical correlations. Several signalling pathways and molecular mediators are known to precipitate GBM, and small‐molecular targets of these mediators have become a favoured thrust area for researchers to develop potent anti‐GBM drugs. Shp2, an important phosphatase of the nonreceptor type protein tyrosine phosphatase (PTPN) subfamily is responsible for master regulation of several such signalling pathways in normal and glioma cells. Thus, inhibition of Shp2 is a logical strategy for the design and development of anti‐neoplastic drugs against GBM. Though tapping the full potential of Shp2 binding sites has been challenging, nevertheless, many synthetic and natural scaffolds have been documented as possessing potent and selective anti‐Shp2 activities in biochemical and cellular assays, through either active‐site or allosteric binding. Most of these scaffolds share a few common pharmacophoric features, a thorough study of which is useful in paving the way for the design and development of improved Shp2 inhibitors. This minireview summarizes the current scenario of potent small‐molecule Shp2 inhibitors and emphasizes the anti‐GBM potential of some important scaffolds that have shown promising GBM‐specific activity in in vitro and in vivo models, thus proving their efficacy in GBM therapy. This review could guide researchers to design new and improved anti‐Shp2 pharmacophores and develop them as anti‐GBM agents by employing GBM‐centric drug‐discovery protocols.

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Maleimides. -The Michael addition of thiols to N-aryl maleimides (I) can be performed in water at ambient temperature. -(KUMAR, V.; MITRA, R.; BHATTARAI, S.; NAIR*, V. A.; Synth. Commun. 41 (2011) 3, 392-404, http://dx.doi.org/10.1080/00397910903576651 ; Dep. Med. Chem., Natl. Inst. Pharm. Educ. Res., Punjab 160 062, India; Eng.) -M. Bohle 30-104

Glioblastoma multiforme (GBM) is among the most critical and aggressive carcinomas of CNS, characterised by poor prognosis, low survival rate and difficult clinical correlations. Current treatment opportunities have proved to be insufficient due to high chemoresistance, and relapse of the disease with enhanced malignancy. Molecular diagnostics and epigenetic profiling of GBM have discovered several signaling pathways and cellular mediators which play key roles in triggering GBM phenotypic manifestations via somatic and genetic aberrations and recruitment of GBM stem-like cells (GSCs). Lysine specific demethylase 1 (LSD1), a flavin-containing oxidoreductase encoded by the KDM1A gene and containing the unique CoREST component, is an important histone modifying enzyme belonging to the histone demethylase (KDM) subfamily and is responsible for master regulation of several signaling pathways in glioma cells. Pharmacological inhibition of LSD1, either individually or in a dual-targeted approach, is a logical strategy for the management of GBM. The current review discusses the role of LSD1 in various epigenetic modulations in differentiated glioma cells and GSCs. The 2D and 3D structural similarities/dissimilarities between LSD1 and MAOs have been analysed and presented along with a detailed discussion on different chemical classes of small molecule LSD1 inhibitors (both standalone and hybrid pharmacophores) that have shown promise in GBM chemotherapy.