STRUCTURE PREDICTION AND IN SILICO DESIGNING OF DRUGS AGAINST KALLIKREIN PROTEIN 12

Objective: Human Kallikrein protein 12 (hK12) might serve as a novel diagnostic and prognostic biomarker, as well as a potential therapeutic target, in gastric cancer.Methods: In this work, a theoretical model of hK12 receptor protein was generated using the concepts of homology modeling and loop modeling. The resulting model was validated with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against hK12 receptor protein using AutoDock Vina in PyRx 0.8. The structure of ligand DB04786 (Suramin), with least binding energy, was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 16 new ligands.Results: The results indicated that the ligand10 bears the minimum binding energy (-12.3 Kcal/mol) with the target protein and thus the prospects of binding are high. The results also clearly demonstrated that the in silico molecular docking studies of selected ligands, i.e., suramin, ligands 5, 6, 10 and 16 with hK12 protein exhibited favourable binding interactions and warranted.Conclusion: Further studies needed for the development of potent inhibitors for the overexpression of hK12 protein making the management of gastric cancer more efficient

PHYTOCHEMICAL AND HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ANALYSIS OF EXTRACT OF PORTULACA QUADRIFIDA LINN.

Objective: Portulaca quadrifida L. is an herbal medicinal plant known for its therapeutics values in urinary and inflammatory disorders. Leaves areuseful in dysentery; the plant can also act as an antihelminthic. The current study dealt to provide details information about Portulaca quadrifida L.including pharmacognostic and phytochemical analysis.Methods: Current investigation involve quality control characterization of plant Portulaca quadrifida L. The plant extract evaluated for phytochemicaland chromatographic analysis. HPLC fingerprint was carried out, which can be used for correct identification of the plant.Results: The plant extract contains alkaloids, tannins, terpenoid and steroid. The present study provides evidence that solvent extract of Portulacaquadrifida L. contain medicinally important bioactive compounds.Conclusion: The present study provides evidence that solvent extract of plant contains medicinally important bioactive compounds and this justifiesthe use of plant species as traditional medicine for treatment of various diseases.Keywords: Portulaca quadrifida L., Phytochemical, Medicinal plant, High-performance liquid chromatography

<i>In silico</i> designing of drugs for the inhibition of AMF-HER2 complex in trastuzumab resistant breast cancer

292-298About 20 to 25% of human metastatic breast cancer over-expresses the human epidermal growth factor receptor 2 (HER2). With the introduction of HER2-targeted therapies, in particular trastuzumab, HER2 status has become more important. The autocrine motility factor (AMF) is a protein factor expressed and secreted by cancer cells. The interaction of AMF with HER2 triggers HER2 phosphorylation, which leads to the development of resistance against trastuzumab. In this work, a theoretical model of AMF was generated using the concepts of homology modeling and loop modeling. The resulting model was validated by Procheck with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against AMF using AutoDock Vina in PyRx 0.8. The structure of compound (DB04493) with least binding energy (-15.5 kcal/mol) was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 20 new ligands. The study revealed that the compound fructose-6-phosphate (DB04493) has the maximum probability to bind with AMF. The combination of AMF inhibitor with trastuzumab can potentiate the growth inhibitory and anti-invasive actions of trastuzumab in breast cancer cells