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  • br Results and discussion br Conclusions

    2020-10-17


    Results and discussion
    Conclusions An optimization study of the dipeptidyl enoates was performed by chemical structure modifications (Fig. 5). Compound FGA50 displaying R configuration at C-3 was more active than its epimer FGA40. Two modifications of the chemical structure of FGA50 were done: the hydroxyl group of the warhead was interchanged by a ketone group resulting into FGA44, and the CBZ group at the P3 site was replaced by a morpholine carbonyl group yielding FGA67. The ketone group remarkably increased the potency, while the morpholine group lowered the calculated lipophilicity. Hence, FGA75 was prepared by combining both moieties: a ketone group at the warhead for having high activity and a morpholine carbonyl group at P3 site for a balanced lipophilicity. The resulting inhibitor FGA75 showed good activity against protozoa Plasmodium falciparum and low lipophilicity. Further SAR studies will be carried out to first optimize efficacy in vitro, and then to provide proof of concept activity in vivo. For in vitro activity against Leishmania, parasites within SMER 3 will be used to ensure that compounds can enter the parasitophorous vacuoles within which parasites reside. This in vitro SAR study will then be followed by a microsomal stability study and “snapshot” pharmacokinetics prior to testing in animal models of infection. Also a preliminary toxicology study in animal models will be carried out to ensure that the compounds are safe.
    Experimental section
    Introduction
    Materials and methods
    Results and discussion
    Conclusion In the present study, a novel milk-clotting cysteine protease from the latex of F. johannis was purified using a simple (one-step) purification procedure and characterized. The plant latex is readily accessible and together with the simplicity of the method, it can be applied to the production of the protease on a pilot plant basis. Its different characteristics and advantages could then be examined and introduce the final product to biotechnology and industry. High milk-clotting activity, the accessibility of raw materials and low susceptibility to autolysis can pave the way for its use in the dairy industry both for milk clotting as a replacement or in combination with calf rennet, and for the enhancement of cheese ripening procedure in order to save time and storing costs for cheese maturation. Besides, due to its high stability at a wide range of pH, temperature, and also towards various denaturant, surfactants, and organic solvents, this protease may turn out to be an effective choice in pharmaceutical and biotechnological industries as well as in detergent formulation.
    Acknowledgements The authors express their gratitude to University of Guilan for the financial support of this project. We greatly appreciate the collaboration of Gilan Pegah and Kalleh dairy companies for some cheese analysis
    Introduction Giardia intestinalis (syn. Giardia duodenalis and Giardia lamblia) is a non-invasive protozoan parasite responsible for a diarrheal disease (giardiasis) that is common in developing countries [1]. It accounts for approximately 280 million symptomatic cases per year [1]. G. intestinalis has two major life cycle stages; the infectious cyst and the disease-causing, replicative trophozoite. Infection is usually initiated by ingestion of cysts in water or food [2]. The infectious dose is very small, only 10 cysts are needed to start an infection [3] and the parasite can cause large water-borne outbreaks [4]. The cysts excyst and release trophozoites after exposure to the acidic environment in stomach and bile and trypsin in the duodenum [5]. After excystation, the released trophozoites adhere to epithelial cells in the upper small intestine of mammals, resulting in abdominal pain, nausea, diarrhea, malabsorption and weight loss [6]. Giardia infections can also lead to post-infection syndromes like irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS) [7].