Metal complexes with organelle specificity and potent but selective cytotoxicity are highly desirable. In this work, we report the synthesis, characterization and cytotoxicity of six novel copper(ii) complexes of the formula [Cu(R-tpy)(N-O)]NO (1-6), where R-tpy is 4'-phenyl-2,2':6',2''-terpyridine (Ph-tpy; 1-3) or 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy; 4-6), N-O is the anion of 8-hydroxyquinoline (HQ in 1, 4), 5-chloro-7-iodo-8-hydroxyquinoline (CQ in 2, 5) or 5-nitro-8-hydroxyquinoline (NQ in 3, 6). The complex [Cu(Fc-tpy)](ClO) (7) has also been prepared as a control and structurally characterized. The optimized geometries and the frontier orbitals of the complexes have been obtained from DFT calculations. The ferrocenyl appended complexes having the anticancer active CQ (in 5) and NQ (in 6) ligands show remarkable cytotoxicity, giving the respective IC values of 0.75 μM and 0.52 μM in HeLa and 1.3 μM and 2.6 μM in MCF-7 cancer cells. The phenyl appended complexes 2 and 3 are less active than their ferrocenyl analogues in both the cells while the complexes of HQ (in 1, 4) are the least active. Interestingly, complexes 4-6 are significantly less toxic to MCF-10A normal cells. The DCFDA, annexin-V-FITC and propidium iodide nuclear staining assays reveal an apoptotic mechanism of cell death which is attributable to the metal-assisted generation of reactive oxygen species. Imaging experiments on HeLa cells reveals that complex 5 accumulates primarily inside the mitochondria. The complexes bind to calf thymus DNA with moderate affinity giving K values in the range of 6.3 × 10-7.4 × 10 M and to HSA protein with significant affinity giving K values in the range of 8.6 × 10-1.3 × 10 M. Their affinity for DNA suggests that mitochondrial DNA could be the target while their affinity for HSA suggests that they could be transported by HSA in the blood. This work is the first report to show that the ferrocenyl appended copper(ii) complexes of hydroxyquinoline ligands are remarkably cytotoxic to cancer cells but significantly less toxic to normal cells.

In the past few decades, genome-based approaches have contributed significantly to vaccine development. Our aim was to identify the most conserved and immunogenic antigens of Streptococcus pneumoniae, which can be potential vaccine candidates in the future. BLASTn was done to identify the most conserved antigens. PSORTb 3.0.2 was run to predict the subcellular localization of the proteins. B cell epitope prediction was done for the immunogenicity testing. Finally, BLASTp was done for verifying the extent of similarity to human proteome to exclude the possibility of autoimmunity. Proteins failing to comply with the set parameters were filtered at each step. Based on the above criteria, out of the initial 22 pneumococcal proteins selected for screening, pavB and pullulanase were the most promising candidate proteins.

Acute Myeloid Leukaemia (AML) is one of the common forms of haematological malignancy in adults. We analysed the prevalence and clinical significance of FMS-like tyrosine kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) mutations in AML patients of North East India. Co-prevalence and clinical significance of three recurrent chromosomal translocations namely t(15; 17), t(8; 21), t(16; 16) and expression of epidermal growth factor receptor (EGFR), flow markers were also documented and co-related with disease progress. We analysed bone marrow aspirates or peripheral blood samples from 165 newly diagnosed AML patients. All clinical samples were analysed by Real Time PCR and DNA sequencing based assays. NPM1 was the most frequently detected mutation in the study population (46/165 = 27.90%, 95% CI 20.75-35.05). FLT3 mutations were detected in 27/165 (16.40%, 95% CI 10.45-22.35) patients with internal tandem duplication (FLT3-ITD) in 24/165 (14.60%, 95% CI 8.91-20.29) and FLT3-D835 in 3/165 (1.80%, 95% CI 0-4.13) patients. NPM1 mutations were associated with a higher complete remission rate and longer overall survival ( < 0.01) compared to FLT3-ITD whereas FLT3-ITD showed adverse impact with poor survival rate ( < 0.01), leukocytosis ( < 0.01) and a packed bone marrow. EGFR expression was more in patients with NPM1 mutation compared to FLT3 mutation ( = 0.09). Patients with FLT3 and NPM1 mutations uniformly expressed CD13 and CD33 whereas CD34 was associated with poor prognosis ( ≤ 0.01) in patients with NPM1 mutation. FLT3-ITD was associated with inferior overall survival. However the clinical significance of FLT3-D835 was not clear due to small number of samples. NPM1 mutation showed better prognosis with increased response to treatment in the absence of FLT3-ITD.

Background & objectives:Vancomycin-resistant enterococci (VRE) have become one of the most challenging nosocomial pathogens with the rapid spread of the multi-drug resistant strain with limited therapeutic options. It is a matter of concern due to its ability to transfer vancomycin resistant gene to other organisms. The present study was undertaken to determine the emergence of vancomycin-resistant enterococci and the vanA gene among the isolates in a tertiary care hospital of North-East India.Methods:A total of 67 consecutive enterococcal isolates from different clinical samples were collected and identified by using the standard methods. Antibiogram was done by disk diffusion method and VRE was screened by the disk diffusion and vancomycin supplement agar dilution method. The minimum inhibitory concentration (MIC) value for vancomycin was determined by E-test. The VRE isolates were analyzed by PCR for vanA gene.Results:A total of 54 (81%) Enterococcus faecalis and 13 (19%) E. faecium were detected among the clinical isolates and 16 (24%) were VRE. The VRE isolates were multidrug resistant and linezolid resistance was also found to be in three. MIC range to vancomycin was 16-32 µg/ml among the VRE. The vanA gene was found in nine of 16 VRE isolates.Interpretation & conclusions:Emergence of VRE and presence of vanA in a tertiary care hospital setting in North-East India indicate toward a need for implementing infection control policies and active surveillance.

DNMT3A R882 mutation plays an important role in CN-AML patients' prognosis and clinical outcomes in the presence and absence of NPM1 and FLT3 mutations.