Browsing by Subject "thiazole"

Sort by: Order: Results:

Now showing items 1-3 of 3
  • Aly, Ashraf A.; El-Emary, Talaat; Mourad, Aboul-Fetouh E.; Alyan, Zainab Khallaf; Bräse, Stefan; Nieger, Martin (2019)
    5-Carbohydrazides and 5-carbonylazides of pyrazolo[3,4-b]pyridines are used to synthesize new heterocyclic derivatives. Some unexpected behaviors are observed in the reactions of the above two species. The structures of the obtained compounds are proved by spectroscopic studies together with elemental and X-ray structure analyses.
  • Aly, Ashraf A.; Bräse, Stefan; Hassan, Alaa A.; Mohamed, Nasr K.; Abd El-Haleem, Lamiaa E.; Nieger, Martin; Morsy, Nesrin M.; Alshammari, Mohammed B.; Ibrahim, Mahmoud A. A.; Abdelhafez, Elshimaa M. N. (2020)
    Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a-e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c-e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4 '-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4 '-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4 '-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC50 of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1.
  • Lamut, Andraž; Skok, Žiga; Barančoková, Michaela; Gutierrez, Lucas J.; Cruz, Cristina; Tammela, Päivi; Draskovits, Gábor; Szili, Petra Éva; Nyerges, Ákos; Pál, Csaba; Molek, Peter; Bratkovič, Tomaž; Ilaš, Janez; Zidar, Nace; Zega, Anamarija; Enriz, Ricardo D.; Kikelj, Danijel; Tomašič, Tihomir (2020)
    Aim: DNA gyrase and topoisomerase IV are essential bacterial enzymes, and in the fight against bacterial resistance, they are important targets for the development of novel antibacterial drugs. Results: Building from our first generation of 4,5,6,7-tetrahydrobenzo[d]thiazole-based DNA gyrase inhibitors, we designed and prepared an optimized series of analogs that show improved inhibition of DNA gyrase and topoisomerase IV from Staphylococcus aureus and Escherichia coli, with IC50 values in the nanomolar range. Importantly, these inhibitors also show improved antibacterial activity against Gram-positive strains. Conclusion: The most promising inhibitor, 29, is active against Enterococcus faecalis, Enterococcus faecium and S. aureus wild-type and resistant strains, with minimum inhibitory concentrations between 4 and 8 mu g/ml, which represents good starting point for development of novel antibacterials. Graphical abstract