Pharmacomodulation on the piperidinol skeleton: Synthesis of novel PIPD1 derivatives as Mycobacterium abscessus agents

Mycobacterium abscessus (M. abscessus) is a rapidly growing mycobacterium which is able to generate different problems in human infections, such as chronic lung diseases, pulmonary diseases and skin infection. M. abscessus is considered as the first emergent opportunistic pathogen and the number of the infections due to this pathogen increases each year. Since the natural multidrug resistance and the absence of specific treatment to fight it, M. abscessus has become a serious problem of the public health. In this context, an original approach of a phenotypic screen was performed and allowed to identify a new piperidinol-based molecule, PIPD1, which exhibits a potent activity against M. abscessus. The goal of this project was to synthesize and characterize some PIPD1-analogs in order to identify the pharmacophore of PIPD1 and develop a Structure-Activity Relationship (SAR) study.