Exploring the Inclusion Complex of an Anticancer Drug with ß-Cyclodextrin for Reducing Cytotoxicity Toward the Normal Human Cell Line by an Experimental and Computational Approach.

The toxicity of any drug against normal cells is a health hazard for all humans. At present, health and disease researchers from all over the world are trying to synthesize designer drugs with diminished toxicity and side effects. The purpose of the present study is to enhance the bioavailability and biocompatibility of gemcitabine (GEM) by decreasing its toxicity and reducing deamination during drug delivery by incorporating it inside the hydrophobic cavity of ß-cyclodextrin (ß-CD) without affecting the drug ability of the parent compound (GEM). The newly synthesized inclusion complex (IC) was characterized by different physical and spectroscopic techniques, thereby confirming the successful incorporation of the GEM molecule into the nanocage of ß-CD. The molecular docking study revealed the orientation of the GEM molecule into the ß-CD cavity (-5.40 kcal/mol) to be stably posed for ligand binding. Photostability studies confirmed that the inclusion of GEM using ß-CD could lead to better stabilization of GEM (≥96%) for further optical and clinical applications. IC (GEM-ß-CD) and GEM exhibited effective antibacterial and antiproliferative activities without being metabolized in a dose-dependent manner. The CT-DNA analysis showed sufficiently strong IC (GEM-ß-CD) binding (Ka = 8.1575 × 1010), and this interaction suggests that IC (GEM-ß-CD) may possibly exert its biological effects by targeting nucleic acids in the host cell. The newly synthesized biologically active IC (GEM-ß-CD), a derivative of GEM, has pharmaceutical development potentiality.

Exploration of inhibitory action of Azo imidazole derivatives against COVID-19 main protease (Mpro): A computational study.

Four novel ionic liquid tagged azo-azomethine derivatives (L1-L4) have been prepared by the condensation reaction of azo-coupled ortho-vaniline precursor with amino functionalised imidazole derivative and the synthesized derivatives (L1-L4) have been characterized by different analytical and spectroscopic techniques. Molecular docking studies were carried out to ascertain the inhibitory action of studied ligands (L1-L4) against the Main Protease (6LU7) of novel coronavisrus (COVID-19). The result of the docking of L1-L4 showed a significant inhibitory action against the Main protease (Mpro) of SARS-CoV-2 and the binding energy (ΔG) values of the ligands (L1-L4) against the protein 6LU7 have found to be -7.7 Kcal/mole (L1), -7.0 Kcal/mole (L2), -7.9 Kcal/mole (L3), and -7.9 Kcal/mole (L4).The efficiency of the ligands has been compared with the FDA approved and clinically trial drugs such as remdesivir, Chloroquin and Hydroxychloroquin and native ligand N3 of main protease 6LU7 to ascertain the inhibitory potential of the studied ligands (L1-L4) against the protein 6LU7. Pharmacokinetic properties (ADME) of the ligands (L1-L4) have also been studied.

Synthesis, characterization and computational study on potential inhibitory action of novel azo imidazole derivatives against COVID-19 main protease (Mpro: 6LU7).

A series of six novel imidazole anchored azo-imidazole derivatives (L1-L6) have been prepared by the simple condensation reaction of azo-coupled ortho-vaniline precursor with amino functionalised imidazole derivative and the synthesized derivatives (L1-L6) have been characterized by different analytical and spectroscopic techniques. Molecular docking studies were carried out to ascertain the inhibitory action of studied ligands (L1-L6) against the Main Protease (6LU7) of novel coronavirus (COVID-19). The result of the docking of L1-L6 showed a significant inhibitory action against the Main protease (Mpro) of SARS-CoV-2 and the binding energy (ΔG) values of the ligands (L1-L6) against the protein 6LU7 have found to be -7.7 Kcal/mole (L1), -7.4 Kcal/mole (L2), -6.7 Kcal/mole (L3), -7.9 Kcal/mole (L4), -8.1 Kcal/mole (L5) and -7.9 Kcal/mole (L6). Pharmacokinetic properties (ADME) of the ligands (L1-L6) have also been studied.

Isaria tenuipes Peck, an entomopathogenic fungus from Darjeeling Himalaya: Evaluation of in-vitro antiproliferative and antioxidant potential of its mycelium extract.

BACKGROUND: Isaria tenuipes is one of the potent species in the members of the genus Isaria, which is well reported to possess multiple bioactive substances of therapeutic importance. Therefore, an in vitro experimental study was carried to evaluate the bioactivities of the crude methanolic extract from the mycelium of this fungus. METHODS: The fungus was authenticated through morphological characters and the species discrepancy was resolved using the nuclear rDNA ITS sequence. The methanolic extract was fingerprinted by FTIR. The antioxidant components in terms of total phenols and flavonoids were determined as gallic acid and quercetin equivalents respectively. Antioxidant activities of the methanolic extract was assessed using 1, 1-diphenyl-2-picrylhydrazyl (DPPH), 2, 2/-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS0+), Fe2+chelating activity, and hydroxyl radical scavenging assays. Cytotoxicity of the extract was determined by [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] (MTT) assay on three cancer cell lines: HeLa, HepG2, and PC3. Apoptosis was further studied by propidium iodide (PI) and Annexin-V/PI staining flow cytometric analysis. Anti-proliferation capacity was studied by colony-forming assay. RESULTS: In the present study total phenol content of the dried methanol extract was 148.09 ± 3.51µg gallic acid equivalent/mg and flavonoid was 9.02±0.95 µg quercetin/mg. The antioxidant activities of methanol-water extract (8:2 v/v) from cultured mycelia of I. tenuipes investigated and evaluated with 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay revealed IC50 value of 5.04mg/ml with an inhibition rate of 74.77% at 10mg/ml and with an iron-chelating assay the chelating ability was recorded to be 86.76% where the IC50 value was 4.43 mg/ml. In comparison among the antioxidant assays, 2,2/-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS0+) and hydroxyl assay exhibited radical scavenging rate of 44.42% and 49.82% respectively at a concentration of 10 mg/ml. The IC50 value of the extract in MTT assay was 43.45µg/ml with HeLa cells, 119.33µg/ml with PC3 cells, and 125.55µg/ml with HepG2 cells. CONCLUSION: In this study, it can be concluded that the crude methanolic extract exhibited potent antioxidant and antiproliferative activities suggesting natural antioxidative and antiproliferative agents.

Complete chloroplast genome of the hot desert herb Fagonia indica (Zygophyllaceae) from south-central Arabia.

The complete chloroplast genome sequences of the hot desert herb Fagonia indica (Zygophyllaceae) is being reported in this study. The total plastome length was 128,379 bp (GC content 34.02%). The gene order in F. indica was found similar to the angiosperm except for the loss of one copy of the IR and by the presence of a single, large inversion that reverses the order of the genes between rbcL and rps16. A total number of 115 unique coding genes which includes 80 protein-coding gene, 31 tRNA genes, and 4 rRNA genes were annotated. The phylogenetic analysis of representative plastomes from the Roisds revealed two distinct clades of Krameriaceae and Zygophyllaceae.

Response surface optimisation of antioxidant extraction from kinema, a Bacillus-fermented soybean food.

The objective of this work was to optimise different parameters (solvent concentration, time and temperature) for antioxidant extraction from kinema, demonstrated by total phenol content (TPC) and DPPH-scavenging activity (DSA), using response surface methodology. A central composite design was performed to determine the effect of solvent concentration (methanol, 30-100%), temperature (30-60°C) and time (30-150min) on the TPC and DSA of the extract. The solvent concentration and temperature had the most significant (p<0.05) effect. The optimum conditions for the TPC extraction and DSA were 100% methanol, 50°C and 30min, in which 140mg of gallic acid equivalent (GAE) g-1 lyophilised extract and 52% DSA were predicted, while 135mg GAE g-1 lyophilised extract and 56% DSA were experimentally obtained. No significant difference (p<0.05) was found between the experimental and predicted values of the response variables.