Physical Sciences and Mathematics Commons^™

Influence Of Conformational Restriction On The Antibacterial Activity And Ribosomal Selectivity Of Aminoglycoside Antibiotics, Michael Gabriel Pirrone

Wayne State University Dissertations

The ever-increasing threat posed by multidrug-resistant infectious bacteria necessitates

the development of novel antibiotics. Aminoglycoside antibiotics are growing in interest due to

their broad spectrum of activity, lack of known drug related allergies, low manufacturing cost,

and their well-studied mechanism of action. The simplification of rational drug design due to the

well-studied mechanism of action is the key to overcoming the issues presented by these drugs,

namely ototoxicity and nephrotoxicity.

A study of the effect of the conformation of the aminoglycoside ring I side chain is

described wherein it was discovered that an increase in a particular conformation augments the …

Synthesis And Biological Evaluation Of Nitrile-Based Inhibitors Of Cysteine Proteases Caged With Ruthenium Complexes, Rajgopal Sharma

Wayne State University Dissertations

Light activated compounds can be used as tools for understanding and solving numerous biological problems. This dissertation focuses on developing ruthenium-based photocages for caging nitrile-based cysteine protease inhibitors. Four research areas pertaining to this dissertation, i) metals in medicine, ii) photocages in biological applications, iii) photodynamic therapy and iv) cysteine cathepsin proteases were briefly surveyed in the introductory chapter. Next, RuII(bpy)2 group was utilized for synthesizing nitrile-based caged CTSK and CTSB inhibitors. Light activated release of inhibitors, followed by toxicity and stability data were studied. Cathepsin enzyme activity inhibition in 2D and 3D assays were established. This work showcased the …