aureus TMPK compared to other bacterial TMPKs and human TMPK have been identified. 11, 25 and 26 Also, human TMPK selectively phosphorylates the D enantiomer of dTMP and its analogs 26 ( Fig. 4A and B). This enantioselectivity of nucleoside-activating enzymes most likely have a strong impact on the efficacy Inhibitor Library in vitro and specificity of new antimicrobial agents. Human TK has very close homology with the TK of S. aureus ATCC12600 however, ( Fig. 2A and B) humanTK1 has a unique KEN box in the C terminal region which is the binding site for ubiquitin ligase and thereby degrades HTK via an ubiquitin proteasome pathway, 15 which is distinctly absent in the S. aureus

TK. In the present study TMPK and TK genes of S. aureus ATCC12600 have been cloned, expressed and characterized. The TMPK and TK kinetics clearly indicated that TMPK and TK are highly active enzymes in this pathogen and showed very close structural similarities with human TMPK and TK. However, absence

of KEN sequence in S. aureus TK aids in the proliferation of this bacteria and the distinct differences observed in the substrate enantioselectivity of human TMPK conclude that dTMP analogs having L specificity could be strong antimicrobial agents. These unique differences correlated with variations in functions probably explains the rapid proliferation of S. aureus in its human host and which can be very serious and life threatening with the infections caused by multi drug resistant strains of PFI-2 S. aureus. All authors have none to declare. “
“Figure options Download full-size image Download as PowerPoint slide Chalcones are well known intermediates for synthesizing various heterocyclic compounds1 like flavones, isoxazoles, pyrazoles, tetrahydro-2-chromens,2 etc. Chalcones either natural or synthetic are known to exhibit various biological activities. Due to the interesting activities of chalcones derivatives as

biological agents, considerable attention has been focused on this class of compounds. Chalcones are known to exhibit antimalarial,3 antibacterial,4 anticancer,5 antileishmanial,6 Dichloromethane dehalogenase antifibrogenic,7 antiinflammatory,8 immunomodulatory,9 cytotoxic and antitrypanosoma cruzi10 activities. Some chalcone derivatives show herbicidal activity11 and substituted chalcones have exhibited fungi static and fungicidal activity. Flavanoids or chromones represent an awfully important group of naturally occurring bioactive compounds. This field of investigation was initiated in 193612 by discovery of citrin, known as ‘Vitamin P’ (P stands for permeability). Flavonoids constitute one of the major classes of naturally occurring and synthetic organic compounds which exhibit significant biological activity.