Novi derivati 9-aminoakridina kao inhibitori botulinum neurotoksina i P. falciparum parazita malarije

Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials.. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50 % is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to the antimalarial activity, the adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI gt 326), indicating that an adamantyl group is a better carrier than a steroidal motif for this indication.Sintetisani su derivati steroidnih i adamantil-akridina i ispitana je njihova inhibitorna aktivnost prema botulinum neurotoksinima (BoNT) i parazitu malarije. Steroidni akridini pokazuju dobru inhibiciju prema kratkom nizu (LCs) BoNT/A i BoNT/B. Ostvarena inhibicija BoNT/B LC od oko 50% je najviša postignuta vrednost akridinskih derivata prema ovom serotipu. Adamantil-akridinski derivati su pokazali najveću antimalarijsku aktivnost (IC50 u opsegu 6-9 nM, SI gt 326), pokazujući da je adamantil-grupa bolji nosač farmakofore u poređenju sa steroidnim, prema ovoj indikaciji.

Supplementary data for the article: Terzić, N.; Konstantinović, J.; Tot, M.; Burojević, J.; Djurković-Djaković, O.; Srbljanović, J.; Štajner, T.; Verbić, T.; Zlatović, M.; Machado, M.; et al. Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials? Journal of Medicinal Chemistry 2016, 59 (1), 264–281. https://doi.org/10.1021/acs.jmedchem.5b01374

Supplementary material for: [https://doi.org/10.1021/acs.jmedchem.5b01374]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2036

New Methods for Evaluation of Spent Fuel Condition during Long-Term Storage in Slovakia

Experiences with an advanced spent nuclear fuel management in Slovakia are presented in this paper. The evaluation and monitoring procedures are based on practices at the Slovak wet interim spent fuel storage facility in NPP Jaslovské Bohunice. Since 1999, leak testing of WWER-440 fuel assemblies are provided by special leak tightness detection system “Sipping in pool” delivered by Framatomeanp with external heating for the precise defects determination. In 2006, a new inspection stand “SVYP-440” for monitoring of spent nuclear fuel condition was inserted. This stand has the possibility to open WWER-440 fuel assemblies and examine fuel elements. Optimal ways of spent fuel disposal and monitoring of nuclear fuel condition were designed. With appropriate approach of conservativeness, new factor for specifying spent fuel leak tightness is introduced in the paper. By using computer simulations (based on SCALE 4.4a code) for fission products creation and measurements by system “Sipping in pool,” the limit values of leak tightness were established

New 9-aminoacridine derivatives as inhibitors of Botulinum neurotoxins and P. falciparum malaria

Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50% is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to antimalarial activity, adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI > 326), indicating that an adamantyl group is a better carries than a steroidal motif for this indication. [Projekat Ministarstva nauke Republike Srbije, br. 172008