Escaping from Flatland: 3D Carborane-Based Bioisosteres of Erlotinib as Potential Anticancer Agents.

ABSTRACT: Phenyl rings are present in nearly 45% of approved small-molecule drugs; however, their flat, aromatic nature can lead to poor solubility, metabolic instability, and limited target selectivity. Carboranes, as three-dimensional boron-rich bioisosteres, may offer a promising alternative to address these limitations. Here, we report the design, synthesis, and biological characterization of novel carborane-based analogs of erlotinib, exploring 3D bioisosterism to enhance anticancer activity. All the carborane-based analogs displayed better in vitro biological behavior than the parent compound, with the para-derivatives (13) and (17) emerging as promising leads, showing 2.5 to >12-fold greater cytotoxicity than erlotinib and up to ∼7-fold selectivities for glioblasto

SUBMITTER: Davila B 

PROVIDER: S-EPMC12573044 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature