New potent ciprofloxacin-uracil conjugates as DNA gyrase and topoisomerase IV inhibitors against methicillin-resistant Staphylococcus aureus

Design, synthesis, and anti-hepatocellular carcinoma of thiopyrimidine/chalcone hybrids as dual STAT3/STAT5 inhibitors

“…35 The target compounds 5a-i were synthesized by heating 6-amino-2-thiouracil and the acylated chalcones 4a-i in dimethylformamide and K 2 CO 3 at 60 °C. 36,37 The 1 H NMR spectra of hybrids 5a-i presented a common singlet at δ 4.68-6.17 ppm assigned to H5 of the pyrimidine ring. Besides, a single signal was found at δ 3.26-3.88 ppm related to the S-CH 2linker group.…”

“…Phosphorylation of STAT3 at Tyr705 and STAT5 at Tyr694 can result in their dimerization, nuclear translocation, binding to DNA, and subsequent transcription. [37][38][39][40] Thus, the degree of STAT3 phosphorylation at Tyr705 and STAT5 phosphorylation at Tyr694 was measured. As demonstrated in Fig.…”

New Ciprofloxacin–Pyrazolopyrimidine Hybrids as Topoisomerase IV and Gyrase Inhibitors against MRSA AUMC 261

“…[7][8][9][10] Many previous studies discussed the idea of hybridization of ciprofloxacin with different chemical structures especially at C7 position of ciprofloxacin to developed a new antibacterial generations of fluoroquinolones. [11][12][13][14][15][16][17][18][19] DNA topoisomerase enzymes are vital for cell viability and are integral to key DNA processes such as transcription and replication. [20] The positive supercoiled DNA can be relaxed by the action of bacterial enzymes, topoisomerase and DNA gyrase.…”

“…Additionally, some of these ciprofloxacin-uracil conjugates exhibit significant inhibitory activity on two crucial bacterial enzymes, DNA gyrase and topoisomerase compared to ciprofloxacin. [11] Based on the above-mentioned studies, we design to modify scaffold III by isosteric replacement of benzimidazole moiety with pyrazolo [3,4] pyrimidine moiety. Hybridization of ciprofloxacin with pyrazolopyrimidine moiety through methylene linker at the piperazinyl-N4 may produce a stronger antibacterial agent, targeting the topoisomerase IV and/or DNA gyrase enzymes with a little tendency of bacterial resistance (Figure 2).…”

“…Notably, some of these ciprofloxacin–uracil conjugates revealed more potent antibacterial activity compared to ciprofloxacin. Additionally, some of these ciprofloxacin–uracil conjugates exhibit significant inhibitory activity on two crucial bacterial enzymes, DNA gyrase and topoisomerase compared to ciprofloxacin [11] …”