The newer synthetic strategies for DNA binding pyrrolobenzodiazepine antibiotics (review)

Abstract

Modern synthetic approaches to DNA binding pyrrolobenzodiazepine antibiotics have been discussed.

Latent Warheads for Targeted Cancer Therapy: Design and Synthesis of pro-Pyrrolobenzodiazepines and Conjugates

“…The resulting monoester 33 was stirred overnight at room temperature, cyclizing smoothly to 1,4- Although small in size, PBD monomers are known to be extremely sequence selective toward DNA, with the 5′-PuGPu sequence being most reactive. 29 On the other hand, many years ago it was found that the dye Hoechst 33258 (Scheme 8, 39) binds to the minor groove of double-stranded B-DNA with a preference for sequences rich in adenine and thymine. 30 Consequently, we designed a hybrid pro-PBD/Hoechst dye 33258 as a novel latent warhead for targeted therapies.…”

“…Although small in size, PBD monomers are known to be extremely sequence selective toward DNA, with the 5′-PuGPu sequence being most reactive . On the other hand, many years ago it was found that the dye Hoechst 33258 (Scheme , 39 ) binds to the minor groove of double-stranded B-DNA with a preference for sequences rich in adenine and thymine .…”

Oxidation of heterocyclic compounds by manganese dioxide (Review)*

“…Two examples of the dehydrogenation of compounds containing a seven-membered heterocycle are also known. Thus, when hexahydropyrrolo[1,4]benzodiazepinone 83 is boiled with MnO 2 in benzene the seven-and five-membered heterocycles are dehydrogenated with the formation of the product 84 [91]. The annelated 1,2,5-benzothiadiazepinedione 85 is converted very easily into compound 86 by the action of MnO 2 [92].…”

Synthesis of novel non-cross-linking pyrrolobenzodiazepines with remarkable DNA binding affinity and potent antitumour activity

“…11 We have been interested in the structural modifications of the PBD ring system and the development of new synthetic strategies. [12][13][14][15][16] In continuation of these efforts, we report a new synthesis of novel mixed dimers of PBD containing the imino function in one of the PBD rings and an amido group in the other, linked at the C8 position by a suitable alkane spacer. Interestingly, the larger sized spacer (n = 5) increases the melting temperature of CT DNA by a significant 17 °C after 18 h incubation at a (PBD)+(DNA) ratio of 1+5 for 1c.…”