Novel pyrimido-pyridazine derivatives: design, synthesis, anticancer evaluation and in silico studies.

Aim: A novel pyrimido-pyridazine derivative for developing anticancer agents was synthesized via Ullmann arylation using an efficient Cu(OAc)2 catalyst. Materials & methods: Compounds were investigated for their anticancer potential, against human breast adenocarcinoma cells, viz. MCF-7, MDA-MB-231 and normal cell line HEK-293. Further, an in vivo study was conducted on lymphoma-bearing mice while in silico analysis was carried out for molecular interactions. Results: Compound 2b displayed significant antitumor activity towards MDA-MB-231 cells through induction of apoptosis and arresting cells in S-phase in vitro, while it significantly increased the lifespan and reduced tumor growth in vivo. An in silico study revealed potent tyrosine-protein kinase inhibitors. Conclusion: Taken together the molecule has the potential to become an effective therapeutic treatment for breast cancer.

Comparative Molecular docking analysis of DNA Gyrase subunit A in Pseudomonas aeruginosaPAO1.

Pseudomonas aeruginosa is an opportunistic bacterium known for causing chronic infections in cystic fibrosis and chronic obstructive pulmonary disease (COPD) patients. Recently, several drug targets in Pseudomonas aeruginosa PAO1 have been reported using network biology approaches on the basis of essentiality and topology and further ranked on network measures viz. degree and centrality. Till date no drug/ligand molecule has been reported against this targets.In our work we have identified the ligand /drug molecules, through Orthologous gene mapping against Bacillus subtilis subsp. subtilis str. 168 and performed modelling and docking analysis. From the predicted drug targets in PA PAO1, we selected those drug targets which show statistically significant orthology with a model organism and whose orthologs are present in all the selected drug targets of PA PAO1.Modeling of their structure has been done using I-Tasser web server. Orthologous gene mapping has been performed using Cluster of Orthologs (COGs) and based on orthology; drugs available for Bacillus sp. have been docked with PA PAO1 protein drug targets using MoleGro virtual docker version 4.0.2.Orthologous gene for PA3168 gyrA is BS gyrAfound in Bacillus subtilis subsp. subtilis str. 168. The drugs cited for Bacillus sp. have been docked with PA genes and energy analyses have been made. Based on Orthologous gene mapping andin-silico studies, Nalidixic acid is reported as an effective drug against PA3168 gyrA for the treatment of CF and COPD.