“…Given the structural similarity between the azinomycin and neocarzinostatin naphthoate, we had antiticipated that the drugs would share a common, intercalative mode of association with duplex DNA. In experiments designed to define the intercalative ability of the azinomycins, we have examined the interaction of the natural agent 1b and the partial structures 2 , 3 , 4 , and 5 with duplex DNA. …”
Evaluation of the sequence selectivity, noncovalent association, and orientation of the DNA cross-linking agent azinomycin B on its duplex DNA receptor is described. A strong correlation between sequence nucleophilicity and cross-linking yield was observed, and steric effects due to the thymine C5-methyl group were identified. Detailed studies on the role of the azinomycin naphthoate using viscometry, fluorescence contact energy transfer, and DNA unwinding assays point to a nonintercalative binding mode for this group. A kinetic assay for agent regioselectivity was used to determine the orientation of binding and covalent cross-link formation.
“…Given the structural similarity between the azinomycin and neocarzinostatin naphthoate, we had antiticipated that the drugs would share a common, intercalative mode of association with duplex DNA. In experiments designed to define the intercalative ability of the azinomycins, we have examined the interaction of the natural agent 1b and the partial structures 2 , 3 , 4 , and 5 with duplex DNA. …”
Evaluation of the sequence selectivity, noncovalent association, and orientation of the DNA cross-linking agent azinomycin B on its duplex DNA receptor is described. A strong correlation between sequence nucleophilicity and cross-linking yield was observed, and steric effects due to the thymine C5-methyl group were identified. Detailed studies on the role of the azinomycin naphthoate using viscometry, fluorescence contact energy transfer, and DNA unwinding assays point to a nonintercalative binding mode for this group. A kinetic assay for agent regioselectivity was used to determine the orientation of binding and covalent cross-link formation.
“…As part of the development of artificial and potent DNA‐cleaving agents based on natural products, the enantiopure azinomycin–lexitropsin hybrid molecules 179 – 181 were synthesized and their DNA‐cleaving activities evaluated 57. For their preparation, the enantiopure carboxylic acids 183 and 184 were obtained from 182 by a known procedure58 employing an asymmetric Sharpless epoxidation, condensation with 3‐methoxy‐5‐methylnaphthalene‐1‐carboxylic acid in the presence of DCC, and oxidative cleavage of the remaining double bond (Scheme ). The acids 183 and 184 were coupled with the N ‐methyl‐4‐aminopyrrole‐2‐carboxylic acids 185 a – c to generate the desired hybrids 179 a – c and 180 a – c , respectively.…”
Natural products play an important role in the development of drugs, especially for the treatment of infections and cancer, as well as immunosuppressive compounds. However, the number of natural products is limited, whereas millions of hybrids as combinations of parts of different natural products can be prepared. This new approach seems to be very promising in the development of leads for both medicinal and agrochemical applications, as the biological activity of several new hybrids exceeds that of the parent compounds. The advantage of this concept over a combinatorial chemistry approach is the high diversity and the inherent biological activity of the hybrids.
“…Im Zuge der Entwicklung künstlicher DNA‐spaltender Wirkstoffe auf Naturstoffbasis wurden die Azinomycin‐Lexitropsin‐Hybride 179 – 181 enantiomerenrein synthetisiert und auf ihre Aktivität untersucht 57. Die Herstellung geht von den enantiomerenreinen Carbonsäuren 183 und 184 aus, die aus 182 auf bekanntem Weg58 durch Sharpless‐Epoxidierung, Kondensation mit 3‐Methoxy‐5‐methylnaphthalin‐1‐carbonsäure und oxidative Spaltung der verbleibenden Doppelbindung erhalten wurden (Schema ). 183 und 184 wurden mit den N ‐Methyl‐4‐aminopyrrol‐2‐carbonsäuren 185 a – c zu den gewünschten Hybriden 179 a – c bzw.…”
The use of ultrasonic dissection in laparoscopic cholecystectomy reduces the incidence of gallbladder perforation and helps the operation to progress. Less experienced surgeons benefit most from ultrasonic dissection, particularly in complicated intraoperative circumstances.
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