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New amphiphilic prodrugs of adefovir and cidofovir
Tichý, Tomáš ; Andrei, G. ; Dračínský, Martin ; Holý, Antonín ; Balzarini, J. ; Snoeck, R. ; Krečmerová, Marcela
New adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl(oxyethyl) chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl unit were prepared from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The antiviral activity of the prodrugs was evaluated in vitro. A loss in the antiviral activities of the hydroxylated decyl(oxyethyl) esters and hexaethyleneglycol esters of PMEA against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anticytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one- to seven-fold lower than that of Cidofovir.
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Acyclic Nucleoside Phosphonates as Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: New Anti-Malarial Chemotherapy Leads
Hocková, Dana ; Holý, Antonín ; Česnek, Michal ; Baszczyňski, Ondřej ; Tichý, Tomáš ; Krečmerová, Marcela ; Janeba, Zlatko ; Skinner-Adams, T. S. ; Naesens, L. ; Keough, D. T. ; de Jersey, J. ; Guddat, L. W.
Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) is a widely recognized target for the discovery of new anti-malarial drugs. Specific acyclic nucleoside phosphonates (ANPs) inhibit HGXPRTase and possess anti-plasmodial activity. Within the framework of a SAR-study, the classical ANPs (e.g. PME-, PMP- and HPMP-derivatives) as well as novel series of compounds were tested to investigate their efficiency and selectivity on the inhibition of P. falciparum, P. vivax and human enzyme.
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Multiprocessor Randomized On-line Scheduling
Tichý, Tomáš
This paper studies randomized on-line non-preemptive scheduling in multiprocessor systems. In this problem each task is specified by its processing time andscheduled on any of $m$ identical processors. The objective is to minimize theexpected mekespan. We prove lemmas and theorems describing $sigma_m$-competitive randomized algorithms on $m$ processors. The main result is an........
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Online competitive algorithms for maximizing weighzed throughput of unit jobs. ITI Series 2003-172
Bartal, Y. ; Chin, F. Y. L. ; Chrobak, M. ; Fung, S. P. Y. ; Jawor, W. ; Lavi, R. ; Sgall, Jiří ; Tichý, Tomáš
We study an online buffer management problem for networks supporting Quality-of-Service (QoS) applications, equivalently as an online scheduling problem forunit-length jobs, where each job is specified by its release time, deadline, and a nonnegative weight (QoS value). The goal is to maximize the emph{weighted throughput}, that is the total weight of scheduled jobs.
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