Carboranes as unique pharmacophores in antitumor medicinal chemistry

• Published in: Molecular therapy. Oncolytics Vol. 24; pp. 400 - 416
• Main Authors: Chen, Yu, Du, Fukuan, Tang, Liyao, Xu, Jinrun, Zhao, Yueshui, Wu, Xu, Li, Mingxing, Shen, Jing, Wen, Qinglian, Cho, Chi Hin, Xiao, Zhangang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.03.2022; American Society of Gene & Cell Therapy; Elsevier
• Subjects: antitumor; cage; carborane; drug design; pharmacophore; Review; cage; carborane; pharmacophore; antitumor; drug design
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2022.01.005

Carborane is a carbon-boron molecular cluster that can be viewed as a 3D analog of benzene. It features special physical and chemical properties, and thus has the potential to serve as a new type of pharmacophore for drug design and discovery. Based on the relative positions of two cage carbons, icosahedral closo-carboranes can be classified into three isomers, ortho-carborane (o-carborane, 1,2-C2B10H12), meta-carborane (m-carborane, 1,7-C2B10H12), and para-carborane (p-carborane, 1,12-C2B10H12), and all of them can be deboronated to generate their nido- forms. Cage compound carborane and its derivatives have been demonstrated as useful chemical entities in antitumor medicinal chemistry. The applications of carboranes and their derivatives in the field of antitumor research mainly include boron neutron capture therapy (BNCT), as BNCT/photodynamic therapy dual sensitizers, and as anticancer ligands. This review summarizes the research progress on carboranes achieved up to October 2021, with particular emphasis on signaling transduction pathways, chemical structures, and mechanistic considerations of using carboranes. [Display omitted] The applications of carboranes in the field of antitumor treatments mainly include BNCT, BNCT/PDT dual sensitizers, and anticancer ligands. This review summarizes the research progress on carboranes as useful pharmacophores in this field, with particular emphasis on signaling transduction pathways, chemical structures, and mechanistic considerations.