Dual targeting of the mitochondrial Lon peptidase 1 and the chymotrypsin-like proteasome activity as a potential therapeutic strategy in malignant astrocytoma models.

Malignant astrocytomas are aggressive primary brain tumors characterized by extensive hypoxia-induced, mitochondria-dependent changes such as altered respiration, increased chymotrypsin-like (CT-L) proteasome activity, decreased apoptosis, drug resistance, stemness, and increased invasiveness. Mitochondrial Lon Peptidase 1 (LonP1) overexpression and increased CT-L proteasome activity are biomarkers of an aggressive high-grade phenotype and found to be associated with recurrence and poor patient survival. In preclinical models, small molecule agents targeting either LonP1 or the proteasome CT-L activity have anti-astrocytoma activity.

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

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.

WITHDRAWN: Dual targeting of mitochondrial Lon peptidase 1 and chymotrypsin-like protease by small molecule BT317, as potential therapeutics in malignant astrocytomas.

The authors have withdrawn their manuscript owing to massive revision and data validation. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Boron-Containing heterocycles as promising pharmacological agents.

The incorporation of the "magic" boron atom has been established as an important new strategy in the field of medicinal chemistry as boron compounds have been shown to form various bonds with their biological targets. Currently, a number of boron-based drugs (e.g.