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Twelve novel analogs of STAT3 inhibitor BP-1-102 were designed and synthesised with the aim to modify hydrophobic fragments of the molecules that are important for interaction with the STAT3 SH2 domain. The cytotoxic activity of the reference and novel compounds was evaluated using several human and two mouse cancer cell lines. BP-1-102 and its two analogs emerged as effective cytotoxic agents and were further tested in additional six human and two murine cancer cell lines, in all of which they manifested the cytotoxic effect in a micromolar range. Reference compound S3I-201.1066 was found ineffective in all tested cell lines, in contrast to formerly published data. The ability of selected BP-1-102 analogs to induce apoptosis and inhibition of STAT3 receptor-mediated phosphorylation was confirmed. The structure–activity relationship confirmed a demand for two hydrophobic substituents, i.e. the pentafluorophenyl moiety and another spatially bulky moiety, for effective cytotoxic activity and STAT3 inhibition.

Twelve novel analogs of STAT3 inhibitor BP-1-102 were designed and synthesised with the aim to modify hydrophobic fragments of the molecules that are important for interaction with the STAT3 SH2 domain. The cytotoxic activity of the reference and novel compounds was evaluated using several human and two mouse cancer cell lines. BP-1-102 and its two analogs emerged as effective cytotoxic agents and were further tested in additional six human and two murine cancer cell lines, in all of which they manifested the cytotoxic effect in a micromolar range. Reference compound S3I-201.1066 was found ineffective in all tested cell lines, in contrast to formerly published data. The ability of selected BP-1-102 analogs to induce apoptosis and inhibition of STAT3 receptor-mediated phosphorylation was confirmed. The structure–activity relationship confirmed a demand for two hydrophobic substituents, i.e. the pentafluorophenyl moiety and another spatially bulky moiety, for effective cytotoxic activity and STAT3 inhibition.

The article analyzes some typical “separation “activities of the United States government at the beginning of the presidency of Donald Trump. Hence, the authors comment how the United States governments work nowadays in “separation” theory under constitutional law perspective. Keywords: United States, government, separation. References: [1] Montesquieu (1996), Tinh thần pháp luật, Nhà xuất bản Giáo dục, Hà Nội.[2] Bộ Ngoại giao Hoa Kỳ, Chương trình thông tin Quốc tế (J W. Peltason biên tập, chú thích), 2004, About America: The Constitution of the United States of America with Explanatory Notes (Nước Mỹ: Hiến pháp Hợp chủng quốc Hoa Kỳ và chú thích), tr 59.[3] The U.S Congress, “Our American Government” 2003 Edition. House Congress Resolution 221 of The U.S Congress 108th, June 20, 2003 https://www.govinfo.gov/content/pkg/CDOC-108hdoc94/pdf/CDOC-108hdoc94.pdf, truy cập ngày 30/3/2020.[4] “Who Is Judge James L. Robart And Why Did He Block Trump's Immigration Order?”, National Public Radio 04/02/2017, https://www.npr.org/2017/02/04/513446463/who-is-judge-james-l-robart-and-why-did-he-block-trumps-immigration-order, truy cập ngày 30/3/2020. [5] Wang, Amy B. “Trump asked for a 'Muslim ban', Giuliani says — and ordered a commission to do it 'legally”. The Washington Post 30/01/2017, https://www.washingtonpost.com/news/the-fix/wp/2017/01/29/trump-asked-for-a-muslim-ban-giuliani-says-and-ordered-a-commission-to-do-it-legally/ truy cập ngày 30/3/2020.[6] Selena Simmons Duffin, “Trump Is Trying Hard To Thwart Obamacare. How's That Going?”, National Public Radio 30/3/2020, https://www.npr.org/sections/health-shots/2019/10/14/768731628/trump-is-trying-hard-to-thwart-obamacare-hows-that-going, truy cập ngày 30/3/2020.[7] Edwin C. Kisiel III, The Electoral College: Federalism and the Election of the American President, A Senior Thesis submitted in partial fulfillment of the requirements for graduation in the Honors Program Liberty University, 2008 Spring, downloaded from http://digitalcommons.liberty.edu/cgi/viewcontent.cgi?article=1052&context=honors truy cập ngày 30/3/2020, pp 16.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Ngoc Lam Pham Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Thesis Title: Synthesis of novel blebbistatin derivatives as myosin inhibitors Myosins constitute a large and diverse superfamily of ATP-dependent motor proteins responsible for actin-based motility. Currently, based on phylogenetic analyses, myosins are classified into at least twenty four groups. The members of this superfamily are involved in several cell processes such as muscle contraction, cytokinesis, organelle transport, cell polarization and signal transduction. Thus, dysfunction and mutation of myosins can cause several diseases. Therefore, design of myosin inhibitors seems to be very attractive research field from the point of view of characterization of intracellular processes as well as development of novel targeted therapy against diseases implicating myosin dysfunction. Nowadays, one of the most well-known and widely used inhibitors of myosin is (S)-blebbistatin. This inhibitor of myosin II has many advantages, nevertheless it possesses also several limiting factors impeding the biological studies such as photosensitivity and low solubility in water. The aim of this Thesis was to...

Endophytic actinomycetes from medicinal plants have been recently reported as the potential producers of antibiotics, anticancer agents and other bioactive compounds. In this study, the distribution and antimicrobial activity of endophytic actinomycetes isolated from Listea cubeba (Lour.) Pers. were investigated. Consequently, the antimicrobial activities of endophytic isolates against eight pathogens, consisting of Salmonella enterica ATCC 14028, Escherichia coli ATCC 11105, Sarcina lutea CNLM, Bacillus cereus ATCC 11778, Proteus vulgaris CNLM, Pseudomonas aeruginosa CNLM, Staphylococcus epidermidis ATCC 12228, Enterobacter aerogenes ATCC 13048 were tested. Total 143 actinomycetes strains were isolated from L. cubeba tissues, in which 53, 23 and 67 strains were respectively obtained from plant samples collected in Thanh Hoa, Hanoi and Phu Tho provinces. Among media used for isolation, the highest number endophytes were from two main media including HV (18.2 %) and SA (16.1 %). Assessment of strains isolated from three kinds of plant tissues, most of endophytes were from roots (n = 65, 45.5 %) and followed by stems (n = 41, 28.7 %) and leaves (n = 37, 25.9 %). Examination of antimicrobial activity of endophytes revealed that 32.9 % of total strains showed inhibitory activity against at least one of the eight tested pathogenic microorganisms. The obtained results indicated that the L. cubeba (Lour.) Pers. could be an extremely rich reservoir for isolation of diverse actinobacteria producing antimicrobial activities and other bioactive compounds.