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.

Evaluation of Antiulcer and Antioxidant Activity of Barleria gibsoniDalz. Leaves.

BACKGROUND: Peptic ulcer is a digestive disorder most commonly found in clinical practice. Given the many side effects of modern medicine, the initial acquisition of fewer side effects, and medication of indigenous drugs, it should be considered as a better alternative for the treatment of peptic ulcer. OBJECTIVE: To assess antiulcer and antioxidant activity of ethanol extract of Barleria gibsoni (EBG) Dalz. leaves in ulcer-induced rats and in vitro antioxidants method, respectively. MATERIALS AND METHODS: Ethanol EBG was screened for antiulcer activity in pylorus ligation-induced ulcer models in Wistar rats. In vitro antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging activity. Total phenol and flavonoid content in the extracts were determined spectrophotometrically. RESULTS: Oral administration of ethanol extract of leaves at doses of 250, 500 mg/kg p.o. reduced significant gastric lesions induced by pylorus ligation-induced ulcer as compared to standard omeprazole (20 mg/kg p.o.). The IC50 values were found to be 150 µg/mL in leaves extract. The ethanol extracts showed good antioxidant capacity in DPPH radical scavenging assay and NO radical scavenging activity when compared to standard. The total phenolic content using Folin-Ciocalteu reagent estimated in 1 mg of leaves extracts was 368 µg and 481 µg with gallic acid equivalent and also the total flavonoid content found to be 240 and 410 µg, respectively, with quercetin equivalence. CONCLUSION: These findings suggest that the leaves of B. gibsoni possessed antiulcer potential and antioxidant compared to standard. This is the first ever report of antiulcer and antioxidant activities in B. gibsoni (Acanthaceae). SUMMARY: In vivo antiulcer and in vitro antioxidant activity of Barleria gibsoni was evaluated.Soxhelt extraction was carried out and extracts were subjected to qualitative phytochemical analysis. Extract obtained by Soxhlation showed higher total phenolic and flavonoid contents.EBG showed DPPH and Nitric oxide scavenging activity indicating its strong antioxidant potential.On pylorus ligation-accumulated secretions and the related ulcers confirm gastric acid output to be the basic cause of gastric ulcers. Ethanol extract of leaves attenuated the gastric volume, free acidity, total acidity and ulcer index thus showing the anti-secretory mechanism.The results of the histopathological investigation of Barleria gibsoni leaves for antiulcer effects using pylorus ligation induced ulcer model in rats laid credence to traditional use of the plant leaves in ulcer treatment. The ethanol extract of leaves demonstrated increase in percentage preventive index compared to omeprazole respectively. From the present study results reveals the antiulcer activity of ethanol extract leaves which is comparable to that of Omeprazole. Abbreviations Used: EBG: Ethanol extract prepared from the leaves of B. gibsoni, ROS: Reactive Oxygen Species, DPPH: 2, 2-diphenyl-1-picrylhydrazyl, NO: Nitric Oxide, IC50: The half maximal inhibitory concentration, m: mg, DNA: deoxyribonucleic acid, GAE: Gallic acid equivalence, AlCl3: Aluminium chloride.