A series of bedaquiline analogs containing H-bond donors were designed as anti-Mycobacterium tuberculosis drugs. A pair of diastereoisomers (R/S- and S/S-isomers) was selected from these designed compounds for synthetic and stereochemical research. The title compounds were synthesized from chiral precursors for the first time and the absolute configurations (ACs) were determined by electronic c...

New treatments for multidrug-resistant tuberculosis (MDR TB) are urgently needed. Two new drugs, bedaquiline and delamanid, have recently been released, and several new drugs and treatment regimens are in the pipeline. Misuse of TB drugs is a principal cause of drug resistance. As new drugs and regimens reach the market, the need to make them available to patients must be balanced with regulati...

Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb o...

XDR (extensively drug-resistant) and pre-XDR tuberculosis (TB) seriously compromise prognosis and treatment possibilities, and inevitably require the use of group V drugs (World Health Organization). The progress of all patients with XDR and pre-XDR TB seen in a specialized unit during 2012 and 2013 and treated with regimens that included at least 6 months of meropenem-clavulanate (MPC), capreo...

The Mycobacterium tuberculosis (Mtb) electron transport chain (ETC) has received significant attention as a drug target, however its vulnerability may be affected by its flexibility in response to disruption. Here we determine the effect of the ETC inhibitors bedaquiline, Q203 and clofazimine on the Mtb ETC, and the value of the ETC as a drug target, by measuring Mtb's respiration using extrace...

Objective: Because infections caused by nontuberculous mycobacteria (NTM) are rapidly increasing globally, a need exists for developing novel antibiotics and discovering the mechanism of resistance. This research was aimed at understanding bedaquiline resistance in model NTM species Mycobacterium marinum ( M. ). Methods: The M strain subjected to mutant selection with different concentrations B...

The objective: to evaluate the efficacy and safety of delamanid in a short-course treatment regimen for patients with MDR/pre-XDR pulmonary tuberculosis Arkhangelsk Region from 2019 2021. Subjects Methods. 32 (4 MDR TB 28 pre-XDR TB) started within combination chemotherapy new drugs, lasted 12 months. All received delamanid, bedaquiline, linezolid, clofazimine, then was compiled depending on cl...