Designing and synthesis of phosphine derivatives of Ru3(CO)12 – Studies on catalytic isomerization of 1-alkenes

In the present study, we have attempted to identify Sacubitril
derivatives as lead compounds for dormant tuberculosis. A
total of twenty-one compounds belongs to a series of the
Sacubitril derivatives 5(a–u) were synthesized using (2R,4S)-5-
([1,1’-biphenyl]-4-yl)-4-(amino)-2-methylpentanoic acid ethyl ester hydrochloride with different isocyanates and isothiocyanates. All the compounds structures were determined by 1 H & 13CNMR spectroscopy, mass spectrometry, and CHN analysis. Compound, 5r, the structure confirmed by single-crystal X-ray diffraction analysis (SXRD). The newly synthesized compounds were screened for their in vitro antituberculosis activity (antiTB) against dormant Mycobacterium tuberculosis H37Rv (ATCC27294). Among the twenty-one compounds, 5p and 5q were exhibited good potent anti-TB activity compared to the
standard drug Ethambutol. Further, the anti-TB activities of the
compounds (5p and 5q) were evaluated against M. tuberculosis
(Mtb) using the nutrient starvation model (NSM). Moreover,
these two compounds, 5p and 5q have shown significant
inhibition of growth of Mtb as compared to the control. To
determine the toxicity nature, the potent anti-TB active
compounds were evaluated against RAW 264.7 cells. Further,
the anti-TB activities of all these compounds have shown a
good correlation to their in-silico molecular docking analysis by
exhibiting strong interactions with the inhibitor Mur-B.