Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs): A new class of agents with high apoptotic activity in chronic myelogenous leukemia K562 cells and in cells from patients at onset and who were imatinib-resistant.

@article{Silvestri2006Pyrrolo12b125benzothiadiazepines,
  title={Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs): A new class of agents with high apoptotic activity in chronic myelogenous leukemia K562 cells and in cells from patients at onset and who were imatinib-resistant.},
  author={Romano Silvestri and Gabriella Marf{\'e} and Marino Artico and Giuseppe La Regina and Antonio Lavecchia and Ettore Novellino and Emanuela Morgante and Carla Di Stefano and Gianfranco Catalano and Giuseppe Filomeni and Elisabetta Abruzzese and Maria Rosa Ciriolo and Matteo Antonio Russo and Sergio Amadori and Roberto Cirilli and Francesco La Torre and Paola Sinibaldi Salimei},
  journal={Journal of medicinal chemistry},
  year={2006},
  volume={49 19},
  pages={
          5840-4
        }
}
Pyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxides (PBTDs) induced apoptosis in human BCR-ABL-expressing leukemia cells. The apoptotic activity was also observed in primary leukemic blasts, obtained from chronic myelogenous leukemia (CML) patients at onset or from patients in blast crisis and who were imatinib-resistant. Compounds 5 and 14 induced apoptosis before BCR-ABL protein expression and tyrosin phosphorylation were affected and activated different caspases in the apoptotic pathway… Expand
Pyrrolo[1,2‐b][1,2,5]benzothiadiazepines (PBTDs) exert their anti‐proliferative activity by interfering with Akt–mTOR signaling and bax:bcl‐2 ratio modulation in cells from chronic myeloid leukemic patients
TLDR
The results presented in this study demonstrate that the PBTDs are identified as restoring the apoptotic pathways both in primary leukemia cells derived from CML patients at onset and inPrimary leukemia cellsderived from C ML‐chemoresistant patients, thus showing their ability to undergo apoptosis. Expand
The Effects of Pyrrolo[1,2‐b][1,2,5]Benzothiadiazepines in MEC1 Cells
TLDR
PBTD (RS2778) inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, in human MEC1 cells, suggesting potential for PBTDs as a therapeutic agent for treatment of CLL. Expand
PYRROLO[1,2-b][1,2,5]BENZOTHIADIAZEPINES (PBTDs) induce apoptosis in K562 cells
TLDR
These results indicate that PBTDs effectively induce apoptosis of K562 leukemia cells through the activation of caspase cascades and indicate that Bcl-2 inhibits PBTD-1 and -3 induced-apoptosis via a mechanism that interferes with cytocrome c release, and the activity ofcaspase-3, which is involved in the execution of apoptosis. Expand
Development of a novel class of pyrrolo-[1,2,5]benzothiadiazepine derivatives as potential anti-schistosomal agents.
TLDR
It is proved that benzodiazepine may serve as a novel structural skeleton for the development of anti-schistosomal agents. Expand
Synthesis of novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)-guanidine derivatives as potential antitumor agents.
TLDR
Novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)guanidine derivatives have been synthesized as potential anticancer agents and relationships between structure and antitumor activity are discussed. Expand
Dibenzo[1,2,5]thiadiazepines Are Non-Competitive GABAA Receptor Antagonists
TLDR
DBTDs used here could be the initial model for synthesizing new GABAA receptor inhibitors with a potential to be used as antidotes for positive modulators of these receptors or to induce experimental epilepsy. Expand
1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: an effective scaffold for the design of either CB1 or CB2 receptor ligands.
TLDR
The results presented here show that the 1-aryl-5-( 1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide may serve as an effective scaffold for the design of either CB(1) or CB(2) receptor ligands. Expand
Synthesis, cannabinoid receptor affinity, molecular modeling studies and in vivo pharmacological evaluation of new substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides. 2. Effect of the 3-carboxamide substituent on the affinity and selectivity profile.
TLDR
The finding of inhibition of food intake following their acute administration to rats, supported the concept that the CB(1) selective compounds 4 and 52 act as antagonists/inverse agonists. Expand
Intramolecular sulfonylamidomethylation of 2-(2-naphthyl) and 2-(1-naphthyl)ethanesulfonamides: synthesis of new class of naphthosultams
New 1,2,4,5-tetrahydronaphtho[1,2-d]3,2-thiazepine 3,3-dioxides and 1,2,4,5-tetrahydronaphtho[2,1-d]3,4-thiazepine 3,3-dioxides were synthesized by aromatic intramolecular sulfonylamidomethylation ofExpand
Azide based routes to tetrazolo and oxadiazolo derivatives of pyrrolobenzodiazepines and pyrrolobenzothiadiazepines
Abstract Tetrazolo- and 1,2,4-oxadiazolo-fused derivatives of the antitumour, antibiotic, DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepines and their pyrrolobenzothiadiazepine derivatives have beenExpand
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PBTD derivatives active in cell cultures were also inhibitory to the recombinant HIV-1 RT in enzyme assays, thus allowing the conclusion that PBTDs are a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Expand
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