The highest ranking compound was found to be the DNP-adenosine, or DNP- nucleoside, which fitted accurately our model in its estimated bioactive conformation. The DNP- 5-BDBD analog and the successive DNP-poly polymer constitute a very promising agent with enhanced drug-likeness potential, when compared to adenosine nucleotides. The polymer of DNP- was constructed based on the poly structure co-crystallized in the active site of the human PARN enzyme. The fact that an adenine based inhibitor substrate was selected was quite encouraging, given PARN��s increased affinity for adenine-based oligonucleotides. However, the latter are too polar to cross the cell membranes and therefore cannot be used as a platform for the putative design for potential PARN inhibitors. On the contrary, the DNP moiety of the DNP-poly substrate contributes amphipathically to the molecule which enables it to be more membrane-permeable compared to poly chains. Tuberculosis remains the leading cause of death by bacterial infection. According to WHO reports, latent infection represents the major pool of worldwide TB cases, making the treatment of latent TB an important strategy towards eradicating the disease. Persistence of Mycobacterium tuberculosis within the host��s macrophages is the hallmark of latent infection. The unique lipids of the mycobacteria cell wall have been shown to contribute to the persistence of mycobacteria within the macrophage and to play an important role in the virulence and pathogenicity of M. tuberculosis. Cholesterol has been shown to play an important role in the entry of mycobacteria into macrophages. Furthermore, M. tuberculosis is capable of using cholesterol as a carbon source inside the macrophage. The catabolism of cholesterol affects the propionate pool in mycobacteria and augments the production of virulence lipids. Propionyl-CoA is converted to methylmalonyl-CoA, which is considered to be the building block of multimethyl-branched mycolic acids such as Phthiocerol Dimycocerosate. Several gene clusters that were shown to be involved in cholesterol degradation are also essential for mycobacterium ACET survival inside the macrophage. The catabolism of the sterol nucleus of cholesterol in M. tuberculosis involves the action of the hsaADCB products of a gene cluster which includes nat, the gene encoding for arylamine N-acteyltransferase. NAT utilises Pr-CoA in addition to acetyl-CoA as an acyl donor, both of which are products of degradation of the alkyl moiety of cholesterol. Both whole genome and candidate gene approaches have shown the importance of this gene cluster in the intracellular survival of mycobacteria. NAT is a cytosolic enzyme that is found in M. tuberculosis and many other organisms. This enzyme catalyses the transfer of an acyl group, usually an acetyl, to an arylamine substrate using a conserved cysteine residue by a Ping-Pong bi-bi mechanism.