Helicobacter pylori is probably the most common chronic bacterial infection in humans and has infected almost half of the world's population. Podophyllotoxin is a lignan compound of plant origin and has great medicinal importance due to its various biological properties. The aim of this study was to investigate the podophyllotoxin as Urease, VacA and cagA inhibitor of Helicobacter pylori. The crystallized structure of podophyllotoxin was received from the Zinc database and used as a ligand. The structure of the ligand was optimized by the mm 2 method with Chem3D v20. 1. 1. 125 software. The ligand was evaluated as an inhibitor against the active site of the urease enzyme, VacA, and cagA by AutodackVina software. The output results were analyzed and evaluated by Discovery Studio v16. 1. 0 software. The best affinity was obtained against VacA =-8. 1 kcal/mol. The highest diversity of links was also reported in VacA. Hydrogen bonds established with VacA against tyrosine=729 and threonine=672, indicating the effectiveness of podophyllotoxin against VacA. Podophyllotoxin against cagA and Urease also showed a variety of hydrogen bonds respectively with lysine, serine, and tyrosine-glutamine, arginine, and asparagine. These results demonstrate the excellent inhibition of podophyllotoxin against Helicobacter pylori. Helicobacter pylori plays a key role in the development of gastric cancer. The transplant conformations predicted in this study showed that podophyllotoxin has valuable inhibitory potential. Therefore, podophyllotoxin may be considered as an anti-Helicobacter pylori agent for further research into drug development.

The binding interaction of novel podophyllotoxin derivative, (3R, 4R)-4-((benzo[d][1, 3]dioxol-5-yl)methyl)-dihydro-3-(hydroxy(3, 4-dimethoxyphenyl) methyl) furan-2(3H)-one (PPT), with calf thymus DNA (ctDNA) has been examined using UVVisible absorption spectrophotometry, fluorescence spectroscopy, viscosity measurement and molecular docking studies. UV-Vis absorption results showed hyperchromic effect and low binding constant value (1. 01×104 M-1), indicating nonintercalative interaction as a binding mode. The competitive fluorescence study also confirmed the obtained results from UV-Vis absorption spectra. Small changes in the viscosity of DNA exhibited that the interaction of PPT with DNA is based on groove binding mode. Molecular docking study showed minor groove interaction and-7. 08 kcal/mol as a calculated energy.

Linum album as one of the endemic perennial plants in Iran is a natural source of lignan compounds. In the present study, the seeds of L. album were collected from its natural habitats in four regions of Iran (Aliabad, Jowkar, Dasht-e Arzhan, Taleqan). The effects of ecotype and gibberellic acid (GA) pretreatment were evaluated on germination traits of L. album seeds in a factorial based on completely randomized design with four replications. Also, the capacity of studied ecotypes in regard to secoisolariciresinol (SECO), podophyllotoxin (PTOX) and 6-methoxy-podophyllotoxin (6-MPTOX) production was assayed under in vitro condition by high performance liquid chromatography (HPLC) based on completely randomized design with four replications. In all studied ecotypes of L. album, seed germination percentage, germination rate and seedling growth was significantly improved in response to GA pretreatment. The obtained sterilized seedlings were used as in vitro explants that were successfully propagated in MS medium without any growth regulators. The in vitro proliferation rate in ecotype of Jowkar in terms of shoot number and plantlet biomass was significantly higher than the other ecotypes. The highest SECO and PTOX contents were extracted in the Dasht-e Arzhan plantlets which were higher (up to four times) than the other ecotypes. Also, the plantlets of Dasht-e Arzhan, Taleqan and Jowkar ecotypes showed the highest content of 6-MPTOX. According to germination, morphological and phytochemicals traits, the ecotype of Dasht-e Arzhan can be considered as a good candidate for breeding programs of improving PTOX production in this plant.

The natural lignan podophyllotoxin, a dimerized product of two phenylpropanoid moieties which occurs in a few plant species, is a pharmacologically important compound for its anticancer activities. Optimization of the in vitro cultures might lead to a renewable source of lignans for medicinal uses. In order to maximize efficiency of podophyllotoxin accumulation via in vitro cultures, the effect of different concentrations of a-Naphthalene acetic acid (NAA) (0, 0.4 and 1 mg/l), Kinetin (Kin) (0, 0.2 and 0.4 mg/l) and combinations of NAA and Kin [(0.4 and 0.2), (0.4 and 0.4), (1 and 0.2) and (1 and 0.4) mg/l] on growth and accumulation of podophyllotoxin in callus, cell culture and in vitro propagated plantlets of Linum album was evaluated. The highest growth and accumulation of podophyllotoxin in callus culture was obtained when it grown under dark condition in comparison to photoperiod.The biomass of cell and callus do not changed under various hormone concentrations. Content of podophyllotoxin was enhanced in cell and callus cultures supplemented with NAA 1 mg/l+Kin 0.4 mg/l. The experiments demonstrated Kin 0.2 or 0.4 mg/l stimulated multiplication and production of podophyllotoxin in shoot culture.