Identification of potential biogenic chalcones against antibiotic resistant efflux pump (AcrB) via computational study.

The cases of bacterial multidrug resistance are increasing every year and becoming a serious concern for human health. Multidrug efflux pumps are key players in the formation of antibiotic resistance, which transfer out a broad spectrum of drugs from the cell and convey resistance to the host. Efflux pumps have significantly reduced the efficacy of the previously available antibiotic armory, thereby increasing the frequency of therapeutic failures. In gram-negative bacteria, the AcrAB-TolC efflux pump is the principal transporter of the substrate and plays a major role in the formation of antibiotic resistance. In the current work, advanced computer-aided drug discovery approaches were utilized to find hit molecules from the library of biogenic chalcones against the bacterial AcrB efflux pump. The results of the performed computational studies via molecular docking, drug-likeness prediction, pharmacokinetic profiling, pharmacophore mapping, density functional theory, and molecular dynamics simulation study provided ZINC000004695648, ZINC000014762506, ZINC000014762510, ZINC000095099506, and ZINC000085510993 as stable hit molecules against the AcrB efflux pumps. Identified hits could successfully act against AcrB efflux pumps after optimization as lead molecules.Communicated by Ramaswamy H. Sarma.

Exploring biogenic chalcones as DprE1 inhibitors for antitubercular activity via in silico approach.

Cases of drug-resistant tuberculosis (TB) have increased worldwide in the last few years, and it is a major threat to global TB control strategies and the human population. Mycobacterium tuberculosis is a common causative agent responsible for increasing cases of TB and as reported by WHO, approximately, 1.5 million death occurred from TB in 2020. Identification of new therapies against drug-resistant TB is an urgent need to be considered primarily. The current investigation aims to find the potential biogenic chalcone against the potential targets of drug-resistant TB via in silico approach. The ligand library of biogenic chalcones was screened against DprE1. Results of molecular docking and in silico ADMET prediction revealed that ZINC000005158606 has lead-like properties against the targeted protein. Pharmacophore modeling was done to identify the pharmacophoric features and their geometric distance present in ZINC000005158606. The binding stability study performed using molecular dynamics (MD) simulation of the DprE1-ZINC000005158606 complex revealed the conformational stability of the complex system over 100 ns with minimum deviation. Further, the in silico anti-TB sensitivity of ZINC000005158606 was found to be higher as compared to the standards against Mycobacterium tuberculosis. The overall in silico investigation indicated the potential of identified hit to act as a lead molecule against Mycobacterium tuberculosis.

Exploration of bioactive molecules from Tinospora cordifolia and Actinidia deliciosa as an immunity modulator via molecular docking and molecular dynamics simulation study.

Tinospora cordifolia and Actinidia deliciosa are the widely used plant in Ayurvedic systems of medicine. Both plants are well known for their immunomodulatory activity. In the current study, in silico exploration was performed using advanced computational techniques such as molecular docking and molecular dynamics simulation approach. Bioactive molecules from the Tinospora cordifolia and Actinidia deliciosa were docked against the Human IL-2. Out of all the docked bioactive molecules, Pygenic acid-B (PubChem CID:146157192) showed the highest negative binding affinity.