Design, Synthesis, and Biological Evaluation of Pyrrolo[2,1-<i>c</i>][1,4]benzodiazepine and Indole Conjugates as Anticancer Agents

Wang, Jhi-Joung; Shen, Yu-Kai; Hu, Wan‐Ping; Hsieh, Ming-Chu; Lin, Fu-Lung; Hsu, Ming-Kuan; Hsu, Ming Lun

doi:10.1021/jm050956q

Cited by 71 publications

(17 citation statements)

References 39 publications

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“…Additionally, the chromophoric properties of these moieties allowed a detailed study of their binding mode to DNA, discussed in Section . Diethylphosphonate ( 69 ), triazolebenzothiadiazine ( 70 ), indole ( 71 ),, and enediyne ( 72 , 73 ) conjugates were synthesized to increase cytotoxicity and in some cases solubility. Two types of hybrid PBDs synthesized by Thurston et al are of particular interest , .…”

Section: Synthetically Produced Pyrrolobenzodiazepinesmentioning

confidence: 99%

Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines

Gerratana

2010

Medicinal Research Reviews

118

143

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Pyrrolobenzodiazepines (PBDs) are sequence selective DNA alkylating agents with remarkable antineoplastic activity. They are either naturally produced by actinomycetes or synthetically produced. The remarkable broad spectrum of activities of the naturally produced PBDs encouraged the synthesis of several PBDs, including dimeric and hybrid PBDs yielding to an improvement in the DNA binding sequence specificity and in the potency of this class of compounds. However, limitation in the chemical synthesis prevented the testing of one of the most potent PBDs, sibiromycin, a naturally produced glycosylated PBDs. Only recently the biosynthetic gene clusters for PBDs have been identified opening the doors to the production of glycosylated PBDs by mutasynthesis and biosynthetic engineering. The present review describes the recent studies on the biosynthesis of naturally produced pyrrolobenzodiazepines. In addition, it provides an overview on the isolation and characterization of naturally produced PBDs, on the chemical synthesis of PBDs, on the mechanism of DNA alkylation, and on the DNA binding affinity and cytotoxic properties of both naturally produced and synthetic pyrrolobenzodiazepines.

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Section: Synthetically Produced Pyrrolobenzodiazepinesmentioning

confidence: 99%

Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines

Gerratana

2010

Medicinal Research Reviews

118

143

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“…Indolic compounds have attracted a lot of attention due to their interesting biological properties. Antioxidant [ 1 , 2 ], anticancer [ 3 , 4 ], antiviral [ 5 ], antiulcer [ 6 ] and wound healing activities [ 7 ] can be mentioned as some of the significant activities associated with the indole nucleus. Likewise, derivatives of dithiocarbazic acid have been proven to exhibit a wide variety of bioactivities such as antimicrobial [ 8 ], anticancer [ 9 ], antibacterial and antifungal [ 10 ] properties.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Cytoprotective Effect of Benzyl N'-(5-Chloro-indol-3-yl-methylidene)-hydrazinecarbodithioate against Ethanol-Induced Gastric Mucosal Injury in Rats

et al. 2012

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Indolic compounds have attracted a lot of attention due to their interesting biological properties. The present study was performed to evaluate the subacute toxicity and anti-ulcer activity of BClHC against ethanol-induced gastric ulcers. Experimental animal groups were orally pre-treated with different doses of BClHC (50, 100, 200 and 400 mg/kg) in 10% Tween 20 solution (vehicle). Blank and ulcer control groups were pre-treated with vehicle. The positive group was orally pretreated with 20 mg/kg omeprazole. After one hour, all groups received absolute ethanol (5 mL/kg) to generate gastric mucosal injury except the blank control group which was administered the vehicle solution. After an additional hour, all rats were sacrificed, and the ulcer areas of the gastric walls determined. Grossly, the ulcer control group exhibited severe mucosal injury, whereas pre-treatment with either derivative or omeprazole resulted in significant protection of gastric mucosal injury. Flattening of gastric mucosal folds was also observed in rats pretreated with BClHC. Histological studies of the gastric wall of ulcer control group revealed severe damage of gastric mucosa, along with edema and leucocytes infiltration of the submucosal layer compared to rats pre-treated with either BClHC or omeprazole where there were marked gastric protection along with reduction or absence of edema and leucocytes infiltration of the submucosal layer. Subacute toxicity study with a higher dose of derivative (5 g/kg) did not manifest any toxicological signs in rats. In conclusions, the present finding suggests that benzyl N'-(5-chloroindol-3-ylmethylidene)hydrazinecarbodithioate promotes ulcer protection as ascertained by the comparative decreases in ulcer areas, reduction of edema and leucocytes infiltration of the submucosal layer.

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“…1). Based on various substituted benzodiazepine analogous, these moieties are exhibited different biological activities like, anti‐inflammatory, antibacterial, antifungal, anticancer, Anti‐HIV, antitumor etc. Moreover, these moieties are responsible for boost the neurotransmitter gamma‐aminobutyric acid at the GABA A receptor mode of action, which resulting anxiolytic, hypnotic, sedative, muscle relaxant and various anticonvulsant properties…”

Section: Introductionmentioning

confidence: 99%

Recyclable Itaconic Acid with Water as Green Catalytic System: Synthesis of Substituted 1,5‐Benzodiazepine Derivatives at Room Temperature

Tamuli

2020

ChemistrySelect

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The construction of new C-N chemical bonds through cocondensation reaction in water media as sole solvent, especially without the use of any metal catalyst has undergoes green protocols. Herein, we describe a water-mediated and metal-free mild protocol for easily accessing of structurally and electronically diverse 1,5-benzodiazepine analogous by using biode-gradable naturally occurring itaconic acid (20 mol%) in 30 minutes with excellent yields. The simplicity in reaction operation, reusability of the catalytic system and simple filtration to get the desired product make this reaction as "green synthetic pathway" upto multi gram scale level.

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Design, Synthesis, and Biological Evaluation of Pyrrolo[2,1-c][1,4]benzodiazepine and Indole Conjugates as Anticancer Agents

Cited by 71 publications

References 39 publications

Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines

Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines

RETRACTED: Cytoprotective Effect of Benzyl N'-(5-Chloro-indol-3-yl-methylidene)-hydrazinecarbodithioate against Ethanol-Induced Gastric Mucosal Injury in Rats

Recyclable Itaconic Acid with Water as Green Catalytic System: Synthesis of Substituted 1,5‐Benzodiazepine Derivatives at Room Temperature

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