The pyrimidine nucleus is an important component of nucleic acids (DNA and RNA) and vitamins (B(2) and folic acid). It is evident from the literature that pyrimidine derivatives possess a wide spectrum of biological activities such as antioxidant, anticancer, antibacterial, and anti-inflammatory activities. On the basis of diverse biological activities, we attempted to synthesize a series of novel bis(2-(pyrimidin-2-yl)ethoxy)alkanes 5a-j in four steps with good yields. 2-Chloropyrimidine (1) was reacted with diethyl malonate in the presence of sodium hydride in dry dimethyl formamide to yield the intermediate diethyl 2-(pyrimidin-2-yl)malonate (2), which on further reaction with sodium chloride and dimethyl sulfoxide yielded ethyl 2-(pyrimidin-2-yl)ethanoate (3). Reduction with sodium borohydride (NaBH(4) ) resulted in the formation of 2-(pyrimidin-2-yl)ethanol (4). This was further reacted with various dibromoalkanes to obtain the title compounds 5a-j. In this current study, we evaluated the antioxidant properties of the title compounds using four in vitro test systems: the 2,2-diphenyl-2-picrylhydrazyl radical-, superoxide radical-, and hydroxyl radical-scavenging assays, and the anti-lipid peroxidation activity test. The title compounds showed promising antioxidant activity when compared to butylated hydroxytoluene. The potency of their antioxidant activity was mainly influenced by the alkyl fragment attached to 2-(pyrimidin-2-yl)ethanol. The ethyl and butyl fragments linked to oxygen led to increased antioxidant activity of the title compounds (i.e., 5b and 5d) in all our in vitro assays.
Staphylococcus aureus a natural inhabitant of nasopharyngeal tract mainly survives as biofilms and possess complete Krebs cycle
which plays major role in its pathogenesis. This TCA cycle is regulated by Isocitrate dehydrogenase (IDH) we have earlier cloned,
sequenced (HM067707), expressed and characterized this enzyme from S. aureus ATCC12600. We have observed only one type of
IDH in all the strains of S. aureus which dictates the flow of carbon thereby controlling the virulence and biofilm formation, this
phenomenon is variable among bacteria. Therefore in the present study comparative structural and functional analysis of IDH was
undertaken. As the crystal structure of S. aureus IDH was not available therefore using the deduced amino sequence of complete
gene the 3D structure of IDH was built in Modeller 9v8. The PROCHECK and ProSAweb analysis showed the built structure was
close to the crystal structure of Bacillus subtilis. This structure when superimposed with other bacterial IDH structures exhibited
extensive structural variations as evidenced from the RMSD values correlating with extensive sequential variations. Only 24%
sequence identity was observed with both human NADP dependent IDHs (PDB: 1T09 and 1T0L) and the structural comparative
studies indicated extensive structural variations with an RMSD values of 14.284Å and 10.073Å respectively. Docking of isocitrate to
both human IDHs and S. aureus IDH structures showed docking scores of -11.6169 and -10.973 respectively clearly indicating
higher binding affinity of isocitrate to human IDH.
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