Identification of new hit to lead magmas inhibitors as potential therapeutics for glioblastoma

• Published in: Bioorganic & medicinal chemistry letters Vol. 91; p. 129330
• Main Authors: Das, Bhaskar C., Lepe, Javier J., Adil Shareef, Mohammed, Lomeli, Naomi, Das, Sasmita, Bota, Daniela A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.07.2023; Elsevier
• Subjects: Anti-glioma agents; Anticancer; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Brain Neoplasms - drug therapy; Carboxamides; Cell Line, Tumor; Cell Proliferation; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Glioblastoma; Glioblastoma - drug therapy; Glioma; Hit to lead; Humans; Life Sciences & Biomedicine; Magmas protein; Oxadiazborole; Oxadiazoles; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Oxadiazoles; Anti-glioma agents; Glioblastoma; Anticancer; Oxadiazborole; Carboxamides; Hit to lead; Magmas protein; DESIGN
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2023.129330

A series of seventeen BT#9 analogues were designed, synthesized, characterized and tested for their anti-glioblastoma potential. Among them, BT-851 and BT-892 displayed promising anti-glioma effect and could serve as templates for magmas inhibitors in the future. [Display omitted] In continuation of our previous efforts for the development of potent small molecules against brain cancer, herein we synthesized seventeen new compounds and tested their anti-gliomapotential against established glioblastoma cell lines, namely, D54MG, U251, and LN-229 as well as patient derived cell lines (DB70 and DB93). Among them, the carboxamide derivatives, BT-851 and BT-892 were found to be the most active leads in comparison to our established hit compound BT#9.The SAR studies of our hit BT#9 compound resulted in the development of two new lead compounds by hit to lead strategy. The detailed biological studies are currently underway. The active compounds could possibly act as template for the future development of newer anti-glioma agents.