Genotoxic effects and mitosis aberrations of chromium (VI) on root cells of Vicia faba and its molecular docking analysis.

Like other heavy metals, Cr (VI) is a powerful carcinogen and mutagen agent. Its toxic effects on plants are well considered. In order to elucidate its adverse effects, the present work aims to study the mitosis aberrations of Cr (VI) on the Vicia faba root-cells and its molecular docking analysis to understand the genotoxicity mechanisms. In-vivo, Vicia faba plants were exposed to 50 and 100 µM Cr (VI) for 48 h. In-silico, molecular docking and molecular dynamics simulation were used to study the interactions between dichromate and tubulin tyrosine ligase T2R-TTL (PDBID: 5XIW) with reference to Colchicine (microtubule inhibitor). According to our results, Cr (VI) affects growth and cell division and also induces many mitosis aberrations such as chromosome sticking, anaphase/telophase bridges, lagging chromosomes and fragmentation during all phases of mitosis. On the one hand, Cr (VI) reduces mitotic index and promotes micronuclei induction. The in-silico results showed that dichromate establishes very strong bonds at the binding site of the tubulin tyrosine ligase T2R-TTL, with a binding affinity of -5.17 Kcal/Mol and an inhibition constant of 163.59 µM. These interactions are similar to those of colchicine with this protein, so dichromate could be a very potent inhibitor of this protein's activity. TTL plays a fundamental role in the tyrosination/detyrosination of tubulin, which is crucial to the regulation of the microtubule cytoskeleton. Its inhibition leads to the appearance of many morphogenic abnormalities such as mitosis aberrations. In conclusion, our data confirm the highest genotoxicity effects of Cr (VI) on Vicia faba root-cells.

Chromone-isoxazole hybrids molecules: synthesis, spectroscopic, MEDT, ELF, antibacterial, ADME-Tox, molecular docking and MD simulation investigations.

A mechanistic study was performed within the molecular electron density theory at the B3LYP/6-311G (d,p) computational level to explain the regioselectivity observed. An electron localization function analysis was also performed, and the results confirm the zwitterionic-type (zw-type) mechanism of the cycloaddition reactions between nitrile oxide and alkylated 4H-chromene-2-carboxylate derivatives and shed more light on the obtained regioselectivity experimentally. In silico studies on the pharmacokinetics, ADME and toxicity tests of the compounds were also performed, and it was projected that compounds 5a, 5b, 5c and 5d are pharmacokinetic and have favorable ADME profiles. Moreover, docking and molecular dynamics investigations were conducted to evaluate the interactions, orientation and conformation of the target compounds on the active sites of four distinct enzymes. The results of this investigation showed that two compounds, 5a and 5c, interacted effectively with the S. aureus active site while maintaining acceptable binding energy.Communicated by Ramaswamy H. Sarma.

Study of the competition between Pi and Cr (VI) for the use of Pi-transporter at Vicia faba L. using molecular modeling.

Recent studies have shown that Cr uses other element transporters such as phosphate transporters to enter cells. The aim of this work is to explore the interaction between dichromate and inorganic phosphate (Pi) in the plant of Vicia faba L. To study this interaction, we used three concentrations of Dipotassium hydrogen phosphate (K2HPO4) 10 mM (Pi10), 50 mM (Pi50) and 100 mM (Pi100) added alone or in combination with potassium dichromate (K2Cr2O7) Cr + Pi10, Cr + Pi50 and Cr + Pi100. In order to investigate the impact of this interaction on morpho-physiological parameters, the biomass, chlorophyll content, proline level, H2O2 level, Catalase and Ascorbate peroxidase activity and Cr-bioaccumulation has been determined. For the molecular scale, the theoretical chemistry was used via molecular docking to explore the various interactions between dichromate Cr2O72-/HPO42-/H2O4P- and the phosphate-transporter. We have selected the eukaryotic phosphate transporter (PDB: 7SP5) as the module. The results showed that K2Cr2O7 negatively affects morpho-physiological parameters and generates oxidative damage (+84% H2O2 than the control), which involved the production of antioxidant enzymes (+147% Catalase and +176% Ascorbate-peroxidase) and Proline (+108%). The addition of Pi improved the growth of Vicia faba L. and induces the partial restoration of the parameters affected by Cr (VI) to the normal levels. Also, it decreased oxidative damage and reduce Cr (VI) bioaccumulation in shoots and roots. Molecular docking has shown that the dichromate structure is more compatible and establishes more bonds with the Pi-transporter which generates a very stable complex compared to HPO42-/H2O4P-. Overall, these results confirmed that there is a strong relationship between dichromate uptake and the Pi-transporter.