Derivati aminokiselina. Dio 1. Sinteza, antivirusno i antitumorsko djelovanje novih estera alfa-aminokiselina s kumarinskim supstituentom

A series of amino acid esters bearing coumarin (3-15) were synthesized and evaluated, in vitro, against HIV-1, and bovine viral diarrhea virus (BVDV). The in vitro cytotoxicity of 3-10 and 12 were assyed against a panel of tumor cell lines consisting of CD4 human T-cells. Compound 14 showed inhibition of HIV-1 with EC50 > 1.6 microg mL-1, meanewhile compound 9 exhibited activity against leukaemia (MT4) with CC50 = 24 micromol L-1).U radu je opisana sinteza estera aminokiselina s kumarinskim ostatkom 3-15. Ispitano je antivirusno djelovanje sintetiziranih spojeva na HIV-1 i goveđi virus diareje (BVDV) te in vitro citotoksičnost spojeva 3-10 i 12 na tumorskim linijama CD4 humanih T-stanica. Spoj 14 pokazao je inhibiciju HIV-1 s EC50 > 1.6 microg mL-1, dok je spoj 9 djelotvoran na leukemiju (MT4) s CC50 = 24 micromol L-1

In vitro antitumorsko i antivirusno djelovanje novih benzotiazola i 1,3,4-oksadiazol-2-tion derivata

A series of new benzothiazole derivatives 6a-h have been synthesized, in five steps, from substituted phenols via the 1,3,4-oxadiazole-2-thiones 5a-h. The in vitro antitumor activity of the compounds obtained was investigated and the benzothiazol derivatives 6d and 6e showed high effects on leukaemia cell lines CCRF-CEM (CC50 = 12 ± 2 µmol L1, 8 ± 1 µmol L1, respectively). These compounds are leading candidates for further development. The title compounds were tested against representatives of several virus families containing single stranded RNA genomes, either positive-sense (ssRNA+), or negative-sense (RNA-), and against double-stranded RNA genomes (dsRNA), as well as some Flaviviridae viruses.U pet reakcijskih koraka sintetizirana je serija novih derivata benzotiazola 6a-h polazeći iz supstituiranih fenola preko 1,3,4-oksadiazol-2-tiona 5a-h. Sintetizirani spojevi ispitani su na antitumorsko djelovanje. Benzotiazol derivati 6d i 6e pokazali su jak učinak na staničnu liniju leukemije CCRF-CEM (CC50 = 12 ± 2, odnosno 8 ± 1 µmol L1). Ti su spojevi predvodni spojevi za daljnji razvoj. Nadalje, novi su spojevi testirani na djelovanje na nekoliko tipova virusa koji sadrže bilo pozitivni (ssRNA+) bilo negativni (RNA-) jednolančani RNA genom ili dvolančani RNA genom (dsRNA), te na neke Flaviviridae viruse

Derivati aminokiselina. Dio 1. Sinteza, antivirusno i antitumorsko djelovanje novih estera alfa-aminokiselina s kumarinskim supstituentom

A series of amino acid esters bearing coumarin (3-15) were synthesized and evaluated, in vitro, against HIV-1, and bovine viral diarrhea virus (BVDV). The in vitro cytotoxicity of 3-10 and 12 were assyed against a panel of tumor cell lines consisting of CD4 human T-cells. Compound 14 showed inhibition of HIV-1 with EC50 > 1.6 microg mL-1, meanewhile compound 9 exhibited activity against leukaemia (MT4) with CC50 = 24 micromol L-1).U radu je opisana sinteza estera aminokiselina s kumarinskim ostatkom 3-15. Ispitano je antivirusno djelovanje sintetiziranih spojeva na HIV-1 i goveđi virus diareje (BVDV) te in vitro citotoksičnost spojeva 3-10 i 12 na tumorskim linijama CD4 humanih T-stanica. Spoj 14 pokazao je inhibiciju HIV-1 s EC50 > 1.6 microg mL-1, dok je spoj 9 djelotvoran na leukemiju (MT4) s CC50 = 24 micromol L-1

Nitroimidazoli. V. Sinteza i anti-HIV djelovanje novih 5-supstituiranih piperazinil-4-nitroimidazol derivata

A series of 2-alkylthio-1-[4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)-piperazin-1-yl]ethanones (3-9) and alkyl-[4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)-piperazin-1-yl)ketones (11-20) as well as the indole analogue 22 were synthesized from 4-nitro-5-piperazinyl imidazole derivative 1, with the aim to develop new non-nucleoside reverse transcriptase inhibitors (NNRTIs). The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compound 4 showed inhibition of HIV-1 (EC50 0.45 µg mL1) and HIV-2 (0.50 µg mL1), while 11 showed inhibition of HIV-1 (EC50 2.48 µg mL1, SI = 4).Iz 4-nitro-5-piperazinil derivata imidazola 1 sintetizirana je serija 2-alkiltio-1-[4-(1-benzil-2-etil-4-nitro-1H-imidazol-5-il)-piperazin-1-il]etanona (3-9) i alkil-[4-(1-benzil-2-etil-4-nitro-1H-imidazol-5-il)-piperazin-1-il)ketona (11-20) te indol analog 22, s ciljem da se razviju novi nenukleozidni inhibitori reverzne transkriptaze (NNRTIs). Novosintetiziranim spojevima ispitano je djelovanje na HIV-1 i HIV-2 u MT-4 stanicama. Spoj 4 pokazao je značajno djelovanje na HIV-1 (EC50 0,45 µg mL1) i HIV-2 (0,50 µg m-1), a spoj 11 na HIV-1 (EC50 2.48 µg mL-1, SI = 4)

A new class of dihaloquinolones bearing N'-aldehydoglycosylhydrazides, mercapto-1,2,4-triazole, oxadiazoline and a-amino ester precursors: synthesis and antimicrobial activity

Reaction of the quinolones 6-8 with hydrazine afforded the hydrazide 9-11 in moderate yields. Condensation of 9 and 11 with CS2 /KOH furnished the potassium salts 13 and 14, respectively, which spontaneously afforded the 3-(1,2,4-triazolyl)-quinolones 15 and 16, respectively, on treatment with hydrazine. Reaction of 9 in refluxing CS2 /KOH gave the 3-(1,2,4-oxadiazolyl)-quinolone 17. Alternatively, 15 was prepared from 17. The azide derivative 12, obtained from 10, furnished the a-amino ester derivative 18, on reaction with the glycine ethyl ester. Coupling of 10 with various sugars gave the N'-aldehydoglycosyl-quinolone-3-yl)carbohydrazides 19a-e. The newly synthesized compounds were screened for their antibacterial activity

Synthesis, X-ray structure, <i>in vitro</i> HIV and kinesin Eg5 inhibition activities of new arene ruthenium complexes of pyrimidine analogs

<p>Three new ruthenium(II)-arene complexes of the general formula [{(η⁶-<i>p</i>-cymene)Ru(L)}₂](Cl)₂), where L are monastrol (<b>L</b>^<b>1</b>), ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-pyrimidine-5-carboxylate (<b>L</b>^<b>2</b>) or its 4-bromophenyl analog (<b>L</b>^<b>3</b>), have been synthesized and characterized by elemental analysis, ¹H, ¹³C, and 2-D NMR spectroscopy. The X-ray diffraction study of complex <b>1</b> showed the presence of a dicationic diruthenium complex where two thioxopyrimidines act as tridentate <i>μ,κN:κ</i>^<i>2</i><i>S</i> ligand, bridging two Ru ions through the pyrimidine nitrogen and sulfur atoms. All new complexes were evaluated <i>in vitro</i> for their antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells using MTT assay. Additionally, complexes <b>1</b>–<b>3</b> were screened for their inhibitory activity against the ATPase enzyme and the motor-protein Kinesin Eg5. Complex <b>1</b> was found to inhibit microtubule-stimulated ATPase activity of kinesin of IC₅₀ = 30 μM (monastrol, IC₅₀ = 10 μM).</p

Nitroimidazoles, Part 3. Synthesis and anti-HIV Activity of New N-Alkyl-4-nitroimidazoles Bearing Benzothiazole and Benzoxazole Backbones

A series of 4-nitroimidazole derivatives bearing substituted piperazines (5, 8, 9, 12, 14, 16, 17, and 19 -21) were synthesized with the aim to develop new non-nucleoside reverse transcriptase inhibitors (NNRTIs). The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. All compounds are inactive, except compound 21 which showed inhibition of HIV-1 with EC 50 0.20 µg/mL, and therapeutic indexes (SI) of 12