Arterolane maleate

A search for alternative Mycobacterium abscessus treatments led to our interest in the two-component regulator DosRS, which, in Mycobacterium tuberculosis , is required for the bacterium to establish a state of nonreplicating, drug-tolerant persistence in response to a variety of host stresses. We show here that the genetic disruption of dosRS impairs the adaptation of M. abscessus to hypoxia, resulting in decreased bacterial survival after oxygen depletion, reduced tolerance to a number of antibiotics in vitro and in vivo, and the inhibition of biofilm formation. We determined that three antimalarial drugs or drug candidates, artemisinin, OZ277, and OZ439, can target DosS-mediated hypoxic signaling in M. abscessus and recapitulate the phenotypic effects of genetically disrupting dosS . OZ439 displayed bactericidal activity comparable to standard-of-care antibiotics in chronically infected mice, in addition to potentiating the activity of antibiotics used in combination. The identification of antimalarial drugs as potent inhibitors and adjunct inhibitors of M. abscessus in vivo offers repurposing opportunities that could have an immediate impact in the clinic.

Environment-friendly fast and accurate mid-infrared spectroscopic methods have been developed for the quantitative analysis of doxorubicin hydrochloride (DOX) and arterolane maleate (ALM) in bulk and marketed formulations. Both transmittance and reflectance modes have been used for the analysis and a comparison has been drawn for better accuracy. The analytical methods were validated in accordance with International Council for Harmonisation (ICH) guidelines

The proposed methods have been successfully developed and validated for the quantification of doxorubicin and arterolane maleate in solid bulk and dosage form. High recovery values in both the modes, while analysing DOX and ALM, indicated good accuracy of the methods. The methods showed excellent repeatability and intermediate precision [% RSD (Relative Standard Deviation < 2.0%]. The assay values of the drugs in solid dosage forms were also found close to the labelled claim.

The proposed Fourier transform infrared (FT-IR) spectroscopic methods were found to be specific, reproducible, valid and could be used as general methods for the quantification of most of the solid drug preparations such as tablets, capsules and powders.