In silico approach of naringin as potent phosphatase and tensin homolog (PTEN) protein agonist against prostate cancer.

Prostate cancer (PC) is one of the major impediments affecting men, which leads approximately 31,620 deaths in both developing and developed countries. Although some chemotherapy drugs have been reported for prostate cancer, they are not effective due to the lack of safety, efficacy and low selectivity. Hence, the novel alternative anticancer agents with remarkable effect are highly appreciable. Natural plants contain several bio-active compounds which have been traditionally used for the various medical treatments. Particularly, naringin is a natural bio-active compound commonly found in the citrus fruits, which have shown numerous biological activities. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene, which activates both lipid phosphates and protein phosphates. The PTEN gene is negative regulator of PI3K/AKT/mTOR pathways, since, this signaling pathway play an essential role in the cell survival, proliferation and migration. In the present in silico investigation, structure based virtual screening, molecular docking, molecular dynamics simulation and Adsorption, Distribution, Metabolism, Excretion (ADME) prediction were employed to determine the binding affinity, stability and drug likeness properties of top ranked screened compounds and naringin, respectively. The results revealed that the complex has good molecular interactions, binding stability (peak between 0.3 and 0.4 nm) and no violations in the Lipinski Rule of 5 in naringin, but the screened compounds violated the drug likeness properties. From the in silico analyses, it is identified that naringin compound might assist in the development of novel therapeutic candidate against prostate cancer. Communicated by Ramaswamy H. Sarma.

Nanosilver crystals capped with Bauhinia acuminata phytochemicals as new antimicrobials and mosquito larvicides.

To develop novel nanoformulated insecticides and antimicrobials, herein we produced Ag nanoparticles (AgNPs) using the Bauhinia acuminata leaf extract. This unexpensive aqueous extract acted as a capping and reducing agent for the formation of AgNPs. We characterized B. acuminata-synthesized AgNPs by UV-vis and FTIR spectroscopy, XRD and TEM analyses. UV-vis spectroscopy analysis of B. acuminata-synthesized AgNPs showed a peak at 441.5 nm. FTIR shed light on functional groups from the phytoconstituents involved in nanosynthesis. XRD of B. acuminata-synthesized AgNPs suggested a face-centered cubic structure, with a highly crystalline nature. TEM of B. acuminata-synthesized AgNPs revealed mean size of 25 nm, with round shape. AgNPs tested at 60 µg/mL inhibited the growth of 5 bacteria and 3 fungal pathogens. In the insecticidal assays on important mosquito species, LC50 of the aqueous extract of B. acuminata leaves on the larvae of Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus were 204.07, 226.02, and 249.24 µg/mL, respectively. The B. acuminata-synthesized AgNPs exhibited higher larvicidal efficacy, with LC50 values of 24.59, 27.19, and 30.19 µg/mL, respectively. Therefore, herein we developed a single-step, reliable, inexpensive, and environmentally non-toxic synthesis process to obtain AgNPs with high bioactivity against pathogens and vectors. Given the effective antimicrobial and larvicidal activity, nanoparticles fabricated using plant extracts and extremely low concentrations of trace elements, such as silver, can be exploited for multipurpose activities. Our results pointed out that B. acuminata-synthesized AgNPs have a promising potential in antimicrobial food packaging, as well as a foliar spray to control plant pathogens in the field, and to synergize the efficacy of fungicidal and larvicidal formulations.

In vitro, fluorescence-quenching and computational studies on the interaction between lipoxygenase and 5-hydroxy-3',4',7-trimethoxyflavone from Lippia nodiflora L.

Lippia nodiflora L. is extensively used in traditional medicine for several medicinal purposes, including their use in inflammatory disorders. In this study, the folk use of L. nodiflora was validated using the isolated natural compound, 5-hydroxy-3',4',7-trimethoxyflavone (HTMF) by in vitro, fluorescence spectroscopic and molecular modeling studies with lipoxygenase (LOX), because LOX plays an essential role in inflammatory responses. In this perspective, the methanol extract and HTMF are shown to demonstrate prominent inhibitory activity against soybean lipoxygenase, with an IC50 value of 21.12 and 23.97 µg/ml, respectively. The data obtained from the spectroscopic method revealed that the quenching of intrinsic fluorescence of LOX is produced as a result of the complex formation of LOX-HTMF. The binding mode analysis of HTMF within the LOX enzyme suggested that hydrogen bond formation, hydrophobic interaction and π-π stacking could account for the binding of HTMF. Molecular dynamics results indicated the interaction of HTMF with LOX and the stability of ligand-enzyme complex was maintained throughout the simulation. The computational results are reliable with experimental facts and provided a good representation for understanding the binding mode of HTMF inside the active site of lipoxygenase enzyme.

Exploration of potential EGFR inhibitors: a combination of pharmacophore-based virtual screening, atom-based 3D-QSAR and molecular docking analysis.

Epidermal growth factor receptor (EGFR) protein tyrosine kinases are over expressed in several human cancers and considered as a promising target for developing novel anticancer drugs. In this study, the ligand-based pharmacophore mapping and atom-based 3D-QSAR approach was carried out on a series of 40 novel pyrrolo[3, 2-d]pyrimidine derivatives acting as EGFR inhibitors. The best pharmacophore hypothesis AAADRR.295 was selected and an atom-based 3D-QSAR model was generated by applying partial least-squares algorithm. The developed model was validated and used as a 3D query in sequential virtual screening study to filter five chemical databases. The obtained compounds were further filtered according to Lipinski rule of five and fitness score. Subsequently, a multistep molecular docking study was employed on the retrieved hits and finally, 12 compounds were prioritized as potential leads against EGFR, which exhibited high docking scores, correlated binding mode to experimentally proven compounds and constructive drug-like properties. The results of this study provide detailed structural insights and emphasize the important binding features of these compounds, which may assists in the design and development of novel EGFR inhibitors.