Pyrido[4′,3′:4,5]pyrrolo[2,1-d][1,2,3,5]tetrazines, a new class of Temozolomide heteroanalogues

Diana, Patrizia; Stagno, Antonina; Barraja, Paola; Carbone, Anna; Montalbano, Alessandra; Martorana, Annamaria; Dattolo, Gaetano; Cirrincione, Girolamo

doi:10.3998/ark.5550190.0010.a01

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…Considering the success gained by molecules derived from the marine environment, our research group synthesized a library of compounds obtained through the structure manipulation of nortopsentin, a natural bis‐indolyl alkaloid isolated from deep‐sea sponge Spongsorites ruetzleri which is characterized by significant antiproliferative activity against the P388 murine leukemia cell line [3] . In particular, we produced many derivatives in which the central imidazole ring was replaced by several five‐membered heterocycles [4–7] …”

Section: Introductionmentioning

confidence: 99%

1,2,4‐Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase

et al. 2020

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A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4‐oxadiazole moiety, was efficiently synthesized. All derivatives were pre‐screened for antiproliferative activity against the National Cancer Institute (NCI‐60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT‐2, Capan‐1, and Panc‐1 cells, eliciting EC50 values in the micromolar and sub‐micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial‐to‐mesenchymal transition markers, including SNAIL‐1/2 and metalloproteinase‐9. Moreover, flow cytometric analysis after Annexin V‐FITC and propidium iodide staining demonstrated that these derivatives enhanced apoptosis of PDAC cells. Keeping with these data, the PathScan intracellular signaling and ELISA array revealed cleavage of caspase‐3 and PARP and a significant inhibition of GSK3β phosphorylation, suggesting this kinase as a potential downstream target of our novel compounds. This was further supported by a specific assay for the evaluation of GSK3β activity, showing IC50 values for the most active compounds against this enzyme in the micromolar range.

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Section: Introductionmentioning

confidence: 99%

1,2,4‐Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase

et al. 2020

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“…The cycloaddition reaction of 2‐diazo‐3‐ethoxycarbonyl‐pyrrolo[2,3‐ c ]pyridine 82 with alkyl‐ or aryl‐isocyanates in dichloromethane at room temperature or at 50 °C under microwave irradiation is reported to yield a series of pyrido[4’,3’:4,5]pyrrolo[2,1‐ d ] [1,2,3,5]tetrazine ring system 84 (Scheme 25). [54] The diazotization of 2‐amino‐3‐ethoxycarbonyl‐pyrrolo[2,3‐ c ]pyridine 82 led to the formation of corresponding diazonium ion 83 . The reaction in dichloromethane at room temperature yielded the products in 30–62% yields in 12–48 h time while the reaction in CEM discover microwave apparatus gave the products in 62–87% yields in just 3 min time.…”

Section: Microwave‐assisted Reactions Of Diazo Compoundsmentioning

confidence: 99%

Synthesis and Chemistry of Diazo Compounds under Microwave Irradiation: A Review

Singh

2022

Asian J Org Chem

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Diazo compounds such as α-diazocarbonyls, diazoalkanes, and diazoarenes are well known compounds in organic chemistry. Their synthetic utility is of paramount importance. They are commonly used as precursors of reactive intermediates like ketenes and carbenoids. Their reactions have been traditionally carried out under thermal or photochemical conditions in inert atmosphere. The synthesis and chemistry of such compounds under microwave irradiation have seen steady growth. The present article critically reviews the application of microwave irradiation in synthesis and chemistry of diazoalkanes and α-diazocarbonyls. The microwave-assisted reactions via ketenes and carbenes with alcohols, thiols, phenols, amines, imines, alkenes, alkynes, and three-membered heterocyclic compounds, etc. are described. These reactions furnish synthetically useful building blocks and also biologically relevant heterocyclic compounds. Most reactions are accelerated by the use of microwave irradiation. There are also some reports revealing that the reactions did not occur by conventional heating but yielded products on irradiation with microwaves. The mechanisms of the reactions where necessary and synthetic and biological relevance of the products are highlighted.

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“…Herein, we would like to report a novel, straightforward, and one-pot synthesis of highly substituted 2-amino (hetero)-indole-3-carboxamides. 2-Amino-indole-3- carboxamides in the past have been synthesized by several step processes, for example, by [3,3]-sigmatropic rearrangement and intramololecular cyclization from N -arylhydroxamic acids and malononitrile, by nucleophilic aromatic substitution reaction with malondinitrile or cyanoaceticacid esters, followed by reduction (eq 1, Scheme ), − or by a four-component reaction of pyridine or 3-picoline, chloroacetonitrile, malononitrile, and aromatic aldehydes, by the Nenitzescu reaction of primary ketene aminals and 1,4-benzoquinones, by the reaction of 2-haloanilines and substituted acetonitriles, − and other methods . Our synthetic approach involves a nucleophilic aromatic substitution reaction of a suitable o -halo-nitro-(hetero)aromate with a cyanoacetamide and a subsequent reductive cyclization.…”

Section: Introductionmentioning

confidence: 99%

One-Pot Synthesis of 2-Amino-indole-3-carboxamide and Analogous

2010

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An efficient one-pot, two-step solution-phase synthetic method was developed to synthesize twenty-three 2-amino-indole-3-carboxamides (3) from 2-halonitrobenzene (1) or heterocyclic analogous and cyanoacetamides (2). In this sequence, first, intermediate 2-cyano-2-(2-nitrophenyl)-acetamide (4) was generated under basic condition via SNAr reaction; after direct addition of hydrochloric acid solution, FeCl3, and Zn powder, indole 3 was generated via reduction/cyclization process.

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Pyrido[4′,3′:4,5]pyrrolo[2,1-d][1,2,3,5]tetrazines, a new class of Temozolomide heteroanalogues

Cited by 5 publications

References 10 publications

1,2,4‐Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase

1,2,4‐Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase

Synthesis and Chemistry of Diazo Compounds under Microwave Irradiation: A Review

One-Pot Synthesis of 2-Amino-indole-3-carboxamide and Analogous

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