Computational molecular perspectives on novel carbazole derivative as an anti-cancer molecule against CDK1 of breast and colorectal cancers via gene expression studies, novel two-way docking strategies, molecular mechanics and dynamics.

With increase in cancer incidences, alternative strategies for disease management are of utmost importance. Carbazole, is a compound that is being studied extensively as an anti-cancer compound. In this work, we aimed to investigate a carbazole derivative against specific cancer types such as breast and colorectal, based on the off-target analyses of carbazole derivative. The present work shortlisted 6 proteins that have an association in both cancer types, and then employed two different molecular docking strategies to examine the binding stability of carbazole derivative: a blind-docking state, where the pockets were undefined and mutation-docking state, where possible mutations were induced within the proteins. The results showed that CDK1 bound best in both states to carbazole derivative, and performed better than an array of positive controls. Molecular dynamic simulations at 100 ns further proved its stability, with carbazole derivative-CDK1-blind and mutated complex having RMSD values between 3.2 and 3.6 Å, and 2.8-3.2 Šrespectively. Molecular-mechanics generalized born and surface area solvation disclosed free energy of binding for the complexes as -28.79 ± 3.97 kcal/mol and -31.86 ± 5.09 kcal/mol respectively, with carbazole derivative bound stably within the binding pocket at every 10 ns of the 100 ns trajectory. Radial distribution functions showed that the bell curve was well within 6 Å, thus showing that carbazole derivative and its atoms do not deviate away from the pocket, suggesting its ability to be used as a good anti-cancer compound against breast and colorectal.

Heavy metal assessment in surface sediments off Coromandel Coast of India: Implication on marine pollution.

The present study investigates the distribution of heavy metals (Fe, Cd, Co, Cr, Cu, Ni, Zn and Pb) in the surface sediments along the Coromandel Coast of Bay of Bengal as an indicator of marine pollution. Pollution indices such as Contamination factor (CF), Enrichment factor (EF) and Geo-accumulation index (I) were performed to assess the spatial distribution and pollution status of the study area. The heavy metal concentration in the study area is closely associated with grain size and organic matter. Both geoaccumulation index and metal contamination factor indicate that the sediments are free from contamination with regards to the metals Cr and Ni, followed by uncontamination to moderate contamination of Co, Cu and Zn. However, sediments are found to be extremely polluted with respect to Cd and Pb. Factor analysis reveals that the accumulation of these heavy metals in the shelf sediments are due to anthropogenic inputs from the adjacent land area.