3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

In silico screening of the effectiveness of natural compounds from algae as SARS-CoV-2 inhibitors: molecular docking, ADMT profile and molecular dynamic studies.

Marine species are known as rich sources of metabolites largely involved in the pharmaceutical industry. This study aimed to evaluate in silico the effect of natural compounds identified in algae on the SARS-CoV-2 Main protease, RNA-dependent-RNA polymerase activity (RdRp), endoribonuclease (NSP15) as well as on their interaction with viral spike protein. A total of 45 natural compounds were screened for their possible interaction on SARS-CoV-2 target proteins using Maestro interface for molecular docking, molecular dynamic (MD) simulation to estimate compounds binding affinities. Among the algal compounds screened in this study, three (Laminarin, Astaxanthin and 4'-chlorostypotriol triacetate) exhibited the lowest docking energy and best interaction with SARS-CoV-2 viral proteins (Main protease, RdRp, Nsp15, and spike protein). The complex of the main protease with laminarin shows the most stable RMSD during a 150 ns MD simulation time. Which indicates their possible inhibitory activity on SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Interaction Analysis of MRP1 with Anticancer Drugs Used in Ovarian Cancer: In Silico Approach.

Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.

Revealing the Effect of MnO2, Activated Carbon and MnO2/Activated Carbon on Chitosan Polymer Host Fabricated Co NPs: Antibacterial Performance and Degradation of Organic Compounds.

MnO2 and MnO2 blended with 1 and 2 weight percent of activated carbon (AC), MnO2/AC1 and MnO2/AC2 were synthesized through the sol-gel method. The pure chitosan (CS) films were cast in the form of films. Similarly, 5 weight% of each MnO2, AC, MnO2/AC1 and MnO2/AC2 was intermingled with the CS to produce different films, such as CS-AC, CS-MnO2, CS-MnO2/AC1 and CS-MnO2/AC2. Zero-valent Co NPs were then supported on these films through the chemical reduction method and expressed as CS@Co, CS-AC@Co, CS-MnO2@Co, CS-MnO2/AC1@Co and CS-MnO2/AC2@Co NPs. All the catalysts were characterized by field emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDS) and X-ray diffraction (XRD) techniques. The synthesized catalysts were used as a dip catalyst against the hydrogenation of 4-nitrophenol (4NP), and for the degradation of methyl orange (MO) and Congo red (CR) dyes. The kapp and R2 values were deduced from pseudo-first-order kinetics for 4NP and MO and zero-order kinetics for CR dye. The kapp values of CS-AC@Co and CS-MnO2/AC1@Co NPs for 4NP hydrogenation were higher than those for any other member of the series, at 1.14 × 10-1 and 1.56 × 10-1 min-1 respectively. Similarly, the rate of CR degradation was highest with CS-AC@Co. The R2 values for 4NP, MO and CR dyes were above 0.9, which indicated that the application of pseudo-first- and zero-order models were appropriate for this study. Furthermore, the antibacterial activity of all the catalysts was evaluated against Pseudomonas aeruginosa and Escherichia coli. The CS-AC@Co NPs exhibited the highest zone of inhibition compared to other catalysts against P. aeruginosa, while all the catalysts were inactive against E. coli. This study reveals that the catalyst can be used for the degradation of other pollutants and for microbial inhibition.

Antibacterial Films of Alginate-CoNi-Coated Cellulose Paper Stabilized Co NPs for Dyes and Nitrophenol Degradation.

The development of a solid substrate for the support and stabilization of zero-valent metal nanoparticles (NPs) is the heart of the catalyst system. In the current embodiment, we have prepared solid support comprise of alginate-coated cellulose filter paper (Alg/FP) for the synthesis and stabilization of Co nanoparticles (NPs) named as Alg/FP@Co NPs. Furthermore, Alginate polymer was blended with 1 and 2 weight percent of CoNi NPs to make Alg-CoNi1/FP and Alg-CoNi2/FP, respectively. All these stabilizing matrixes were used as dip-catalyst for the degradation of azo dyes and reduction of 4-nitrophenol (4NP). The effect of initial dye concentration, amount of NaBH4, and catalyst dosage was assessed for the degradation of Congo red (CR) dye by using Alg-CoNi2/FP@Co NPs. Results indicated that the highest kapp value (3.63 × 10-1 min-1) was exhibited by Alg-CoNi2/FP@Co NPs and lowest by Alg/FP@Co NPs against the discoloration of CR dye. Furthermore, it was concluded that Alg-CoNi2/FP@Co NPs exhibited strong catalyst activity against CR, and methyl orange dye (MO) degradation as well as 4NP reduction. Antibacterial activity of the prepared composites was also investigated and the highest l activity was shown by Alg-CoNi2/FP@Co NPs, which inhibit 2.5 cm zone of bacteria compared to other catalysts.