OBJECTIVE: Aim of the present study was to analyse the molecular interaction of nitrogen heterocyclic based drugs (hydroxychloroquine, remdesivir and lomefloxacin) with various SARSCoV- 2 proteins (RdRp, PLPro, Mpro and spike proteins) using a molecular docking approach.
METHODS: We have performed docking study using PyRx software, and Discovery Studio Visualizer was used to visualise the molecular interactions. The designed nitrogen heterocyclic analogues were checked for Lipinski's rule of five, Veber's Law and Adsorption, Distribution, Metabolism, and Excretion (ADME) threshold. After obtaining the docking results of existing nitrogen heterocyclic drugs, we modified the selected drugs to get molecules with better affinity against SARS-CoV-2.
RESULTS: Hydroxychloroquine bound to RdRp, spike protein, PLPro and Mpro at -5.2, -5.1, -6.7 and -6.0 kcal/mol, while remdesivir bound to RdRp, spike protein, PLPro, and Mpro at -6.1, -6.9, -6.4 and -6.9 kcal/mol, respectively. Lomefloxacin bound to RdRp, spike protein, PLPro and Pro at -6.4, -6.6, -7.2 and -6.9 kcal/mol. ADME studies of all these compounds indicated lipophilicity and high gastro intestine absorbability. The modified drug structures possess better binding efficacy towards at least one target than their parent compounds.
CONCLUSION: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing the potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity.
KEY FINDINGS: The major bioactive compounds implicated in the therapeutic effects of Polygonum genus include phenolic and flavonoid compounds, anthraquinones and stilbenes, such as quercetin, resveratrol, polydatin and others, and could serve as potential drug leads or as adjuvant agents. Data from in-silico network pharmacology and computational molecular docking studies are also highly helpful in identifying the possible drug target of pathogens or host cell machinery.
SUMMARY: We provide an up-to-date overview of the data from pharmacodynamic, pharmacokinetic profiles and preclinical (in-vitro and in-vivo) investigations and the available clinical data on some of the therapeutically important compounds of genus Polygonum L. and their medical interventions, including combating the outbreak of the COVID-19 pandemic.
DESIGN: The LAB strains isolated from Malaysian fermented foods, Lactobacillus brevis FT 6 and Lactobacillus plantarum FT 12, were assessed for their antimicrobial properties against Porphyromonas gingivalis ATCC 33277 via disc diffusion assay. Anti-biofilm properties were determined by treating the overnight P. gingivalis ATCC 33277 biofilm with different concentrations of LAB cell-free supernatant (LAB CFS). Quantification of biofilm was carried out by measuring the optical density of stained biofilm. The ability of L. brevis FT 6 and L. plantarum FT 12 to tolerate salivary amylase was also investigated. Acid production with different sugars was carried out by pH measurement and screening for potential antimicrobial organic acid by disc diffusion assay of neutralised probiotics CFS samples. In this study, L. rhamnosus ATCC 7469, a commercial strain was used to compare the efficacy of the isolated strain with the commercial strain.
RESULTS: Lactobacillus brevis FT 6 and L. plantarum FT 12 possess antimicrobial activity against P. gingivalis with inhibition diameters of more than 10 mm, and the results were comparable with L. rhamnosus ATCC 7469. The MIC and MBC assay results for all tested strains were recorded to be 25 µl/µl concentration. All LAB CFS reduced biofilm formation proportionally to the CFS concentration and tolerated salivary amylase with more than 50% viability. Overnight cultures of all lactic acid bacteria strains showed a pH reduction and neutralised CFS of all lactic acid bacteria strains did not show any inhibition towards P. gingivalis.
CONCLUSIONS: These results indicate that the isolated probiotics have the potential as probiotics to be used as a supportive oral health treatment, especially against a periodontal pathogen, P. gingivalis.
RESULTS: AAE could significantly lengthen the mean lifespan, 50% survival days, and maximum lifespan of D. melanogaster, especially when the amount of AAE added reached 6.68 mg mL-1, the mean lifespan of both female and male flies increased by 23.74% and 22.30%, respectively, indicating the effective life extension effect of AAE. At the same time, AAE could improve the climbing ability and tolerance to hydrogen peroxide in D. melanogaster. In addition, the addition of AAE effectively increased the activities of copper-zinc-containing superoxide dismutase, manganese-containing superoxide dismutase and catalase in D. melanogaster and reduced the contents of malondialdehyde. Moreover, when reared with diets containing AAE, the expression of antioxidant-related genes SOD1, SOD2 and CAT was up-regulated in D. melanogaster and down-regulated for MTH genes.
CONCLUSION: The study indicates that AAE effectively enhances the antioxidant capacity of D. melanogaster and has potential applications as an antioxidant and anti-ageing agent in the nutraceutical industry. © 2024 Society of Chemical Industry.
METHODS: Adult female SD rats were injected with 2 mg/kg 17β-oestradiol (E2) to synchronize their oestrous cycle. A day after injection, uteri were removed for in-vitro contraction studies. The dose dependent effect of Ficus deltoidea aqeous extract (FDA) on the tension produced by the isolated rat's uteri was determined. The effects of atropine (2×10(-8) M), atosiban (0.5 IU), THG113.31 (10 μM), oxodipine (0.25 mM), EDTA (1 mM), 2-amino-ethoxy-diphenylborate (2-APB) (40 mM) and thapsigargin (1 mM) on the maximum force of contraction (Emax) achieved following 2 mg/ml FDA administration were also investigated.
RESULTS: FDA induced in-vitro contraction of the isolated rat's uteri in a dose-dependent manner. Administration of atropine, atosiban and THG113.31 reduced the Emax with atosiban having the greatest effect. The Emax was also reduced following oxodipine and EDTA administration. There was no significant change observed following 2-APB administration. Thapsigargin, however, augmented Emax.
CONCLUSIONS: FDA-induced contraction of the isolated rat's uteri is mediated via multiple uterotonin receptors (muscarinic, oxytocin and prostaglandin F2α) and was dependent on the extracellular Ca2+. Contraction, however, was not dependent on the Ca2+ release from the internal stores. This in-vitro study provides the first scientific evidence on the claimed effect of Ficus Deltoidea on uterine contraction.