[2,1-c][1,4]benzodiazepine (PBD)-distamycin hybrid inhibits DNA binding to transcription factor Sp1.
We designed and synthesized the hybrid 6, prepared combining the minor groove binders distamycin A and pyrrolo [2,1-c][1,4] benzodiazepine (PBD) 4, related to the natural occurring anthramycin (2) and DC-81 (3). In this paper, the effects of the compound 6 on molecular interactions between DNA and transcription factor Sp1 were studied. The results obtained demonstrate that PBD-distamycin hybrid is a powerful inhibitor of Sp1/DNA interactions.
Baraldi
P G
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
Cacciari
B
B
Guiotto
A
A
Romagnoli
R
R
Spalluto
G
G
Leoni
A
A
Bianchi
N
N
Feriotto
G
G
Rutigliano
C
C
Mischiati
C
C
Gambari
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000378:metabolism; D004214:Distamycins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D007939:Leukemia L1210 / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
C421502:3-(1-methyl-4-(1-methyl4-(1-methyl-4-(8-(2'-carboxamidoethyloxy)-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5-one)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidine; D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D004273:DNA, Neoplasm; D004214:Distamycins; D016329:Sp1 Transcription Factor; C030000:stallimycin