Development of inhibitors of mycobacterial ribonucleotide reductase

Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance

“…alternative to overcome the metabolic instability of TSCs [55]. In order to include more NNN donors into the study, the previously reported arylhydrazones 4a-c [13] were incorporated to the study and the commercially available arylhydrazones 4d-h (box IV, Figure 1, 2) were purchased To further increase the similarity of the newly designed compounds to 1a, chemical entities were combined in the four compounds presented in box VII ( Figure 2): in 7a the non-isatin moiety of 1a is dimerized.…”

Development of Effective Drug Combinations for the Inhibition of Multiply Resistant Mycobacteria, Especially of the <i>Mycobacterium avium </i>Complex

“…Considering the section of the DNA/RNA biosynthesis pathway depicted in figure 1, it may be assumed that a synergistic inhibitory effect is obtained by combining ribonuclcoside diphosphate reductase (RDR) inhibitors with known drugs used for the treatment of tu berculosis, as for instance INH, RAMP or EMB, which inhibit NADPH-dependent reac tions (like DHFR catalysis [14]) and RNA syn thesis [15] bacterium tuberculosis and M. avium [9,10,16]. As suggested by the biosynthesis pathway, these new antimycobacterials (e.g.…”

Investigations on the Mechanism of Action of the Novel Antitumor Agents 2-Benzothiazolyl, 2-Benzoxazolyl, and 2-Benzimidazolyl Hydrazones Derived from 2-Acetylpyridine

“…These authors subsequently showed that replacement of the TSC side chain by a 2-pyridyl hydrazone moiety leads to a drastic reduction of in vivo toxicity while the desired therapeutic activity was retained [13] . These compounds were also shown to be potent inhibitors of ribonucleotide reductase activity [14] .…”

“…Schaper et al have recently proposed that the in vivo toxicity of α-(N)-heteroaromatic TSCs might be due to the release of toxic H 2 S during their metabolism [13] . These authors subsequently showed that replacement of the TSC side chain by a 2-pyridyl hydrazone moiety leads to a drastic reduction of in vivo toxicity while the desired therapeutic activity was retained [13] .…”