166,841 research outputs found
Tadashi Asai at Hill Air Force Base, 1965. Asai married a Japanese girl.
No full textPhoto of Tadashi Asai at Hill Air Force Base, 1965
Benzothiadiazole derivatives endowed with STAT3 inhibition
No full textBENZOTHIADIAZOLE DERIVATIVES ENDOWED WITH STAT3
INHIBITION
Arianna Gelain (1), Matteo Mori (1), Ettore Gilardoni (1), Luca Regazzoni (1), Alessandro Pedretti (1),
Diego Colombo (2), Gary Parkinson (3), Akira Asai (4), Fiorella Meneghetti (1), Stefania Villa (1)
1) Department of Pharmaceutical Sciences, University of Milan, via L. Mangiagalli 25, 20133 Milan, Italy
2) Department of Medical Biotechnology and Translational Medicine, University of Milan, via C. Saldini 50, 20133 Milan,
Italy
3) Department of Pharmaceutical and Biological Chemistry – UCL School of Pharmacy, University College London, 29/39
Brunswick Square, WC1N 1AX London, United Kingdom
4) Center for Drug Discovery – Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku,
422-8526 Shizuoka, Japan
Signal Transducer and Activator of Transcription 3 (STAT3) is a latent cytoplasmic protein over-expressed in
various cancer cell lines1,2. As a part of our ongoing research focused on compounds showing STAT3 SH2
domain inhibiting activity3,4, by a virtual screening approach, we identified 5,6-dimethyl-1H,3H
-2,1,3-benzothiadiazole-2,2-dioxide (1) as potential inhibitor. Several derivatives were synthesized (Figure 1)
and tested. Since compound 1 exhibited the most interesting activity (IC50 = 15.8 ± 0.6 μM by
AlphaScreen-based assay), we decided to investigate the mechanism of its activity by liquid chromatography,
MS and UV studies, discovering compound 1 unexpected interaction also with cysteine residues5.
Figure 1 . Benzothiadiazole-2,2-dioxide derivatives set
References
1) Darnell, J. Jr Science, 1997, 277, 1630-1635
2) Turkson, J. and Jove R. Oncogene, 2000, 19, 6613-6626
3) Meneghetti, F.; Villa, S.; Masciocchi, D.; Barlocco, D.; Toma, L.; Han, D.C.; Kwon, B.M.; Ogo, N.; Asai, A.; Legnani, L.;
Gelain, A. European J. Org. Chem. 2015, 2015, 4907–4912
4) Porta, F.; Facchetti, G.; Ferri, N.; Gelain, A.; Meneghetti, F.; Villa, S.; Barlocco, D.; Masciocchi, D.; Asai, A.; Miyoshi,
N.; Marchianò, S.; Kwon, B.M.; Jin, Y.; Gandin, V.; Marzano, C.; Rimoldi, Eur. J. Med. Chem. 2017, 131, 196–206
5) Mori, M.; Gilardoni, E.; Regazzoni, L.; Pedretti, A.; Colombo, D.; Parkinson, G.; Asai, A,; Meneghetti, F.; Villa, S.;
Gelain, A., Molecules 2020, 25(15), 3509
[Report to Chief J. E. Curry, by an unknown author #1]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
[Report to Chief J. E. Curry, by an unknown author #2]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
New rosmaricine derivates as anticancer agents
No full textRosmaricine (Fig.1) is a diterpenoid aminocompound obtained from dried leaves of Rosmarinus officinalis L. treated with ammonia in the presence of air. It is an alkaloidal artifact formed through a complex reaction between some oxidation derivatives of carnosic acid and the ammonia used to liberate the bases supposed to be present in the ethanolic extract.1,2
Rosmaricine is structurally similar to the natural diterpenes carnosol and rosmanol, both endowed with antioxidant, radical scavenger and antiproliferative activities through a mechanism that involve, among others, NF-kB and STAT-3 inhibition.3
In view of the growing interest on terpenoid compounds as potential antitumoral drugs and following our recent studies on sulphurated drug-hybrids as multitarget anticancer agents,4,5 we synthesized three new derivatives through the condensation of the amino group of rosmaricine with some sulfurated carboxylic acids, containing a thiosulfonate or allyldisulfide or a dithiolethione moiety (Fig. 1) and investigated their ability to inhibit STAT-3 and NF-kB transcription factors as well as their antiproliferative activity on a human cancer cell line.
Results showed that rosmaricin and its derivatives inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range. In addition, they were able to strongly and selectively bind STAT-3 SH2 domain in an Alpha Screen assay and were also able to inhibit the NF-kB transcriptional activity in HCT-116 cell line.
The obtained data underline the interesting profile of these compounds which are worthy of further investigation as potential multitarget anticancer agents.
References
1. E. Wenkert, A. Fuchs, J.D. McChesney J.Org. Chem. 1965, 30, 2931-2934.
2. A. Boido, F. Savelli, F. Sparatore Il Farmaco 1994, 49, 111-114.
3. C. Lai, J. H. Lee, C. Ho, C. B. Liu, J. Wang, J. Wang, M. Pan J. Agric. Food Chem. 2009, 57, 10990-10998.
4. Gabriele E.; Barteselli A.; Moiana V.; Porta F.; Gelain A.; Asai A.; Sparatore A. Methanethiosulfonate derivatives as ligands of STAT3-SH2 domain. “Tefarco NFPC8” (Parma, Italy, 9-11 June 2014); Poster communication P-18.
5. Gabriele E.; Brambilla D.; Ferri N.; Asai A.; Sparatore A. New sulfurated cinnamic acid derivative as multitarget anticancer agents. Book of Abstract – SIMCC2015 - Spanish-Italian Medicinal Chemistry Congress (Barcellona, Spain - July 12-15, 2015) - P-90
Special hypergeometric motives and their -functions: Asai recognition
No full textInternational audienceWe recognize certain special hypergeometric motives, related to and inspired by the discoveries of Ramanujan more than a century ago, as arising from Asai -functions of Hilbert modular forms
Murder on the mountain: author talk with Peter J. Wosh
No full textAuthor talk by Peter J. Wosh on May 5th, 2022, on his book, "Murder on the Mountain: crime, passion, and punishment in gilded age New Jersey.
Mr. Melvin J. Collier, RWWL AUC, June 2011
No full textThis video is a conversation with Mr. Melvin J. Collier. Mr. Collier talks about his book, "From Mississippi to Africa: A Journey of Discovery". Daniel Le, AUC Woodruff Library, is the interviewer
A Tripartite Post-Recession Rebalancing
No full textIn this latest Advance & Rutgers Report, entitled “A Tripartite Post-Recession Rebalancing,” Dean James W. Hughes and Professor Joseph J. Seneca deliver an incisive assessment of the current market conditions and obstacles in the path of our economic recovery. They offer a statistical cautionary tale that the private and public sector need to hear and acknowledge in order for the economy to make continued progress.This report was published as Issue Paper Number 7, November 2011, in Advance & Rutgers Report
Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of meson decays to J/ψη and J/ψη′
No full textFirst evidence of the B 0 → J / ψ ω decay is found and the B s 0 → J / ψ η and B s 0 → J / ψ η ′ decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb -1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV. The branching fractions of these decays are measured relative to that of the B 0 → J / ψ ρ 0 decay:frac(B (B 0 → J / ψ ω), B (B 0 → J / ψ ρ 0)) = 0.89 ± 0.19 (stat) - 0.13 + 0.07 (syst),frac(B (B s 0 → J / ψ η), B (B 0 → J / ψ ρ 0)) = 14.0 ± 1.2 (stat) - 1.5 + 1.1 (syst) - 1.0 + 1.1 (frac(f d, f s)),frac(B (B s 0 → J / ψ η ′), B (B 0 → J / ψ ρ 0)) = 12.7 ± 1.1 (stat) - 1.3 + 0.5 (syst) - 0.9 + 1.0 (frac(f d, f s)), where the last uncertainty is due to the knowledge of f d / f s, the ratio of b-quark hadronization factors that accounts for the different production rate of B 0 and B s 0 mesons. The ratio of the branching fractions of B s 0 → J / ψ η ′ and B s 0 → J / ψ η decays is measured to befrac(B (B s 0 → J / ψ η ′), B (B s 0 → J / ψ η)) = 0.90 ± 0.09 (stat) - 0.02 + 0.06 (syst)
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