Synthesis and antiproliferative activity of 3-(2-chloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one

Maggio, Benedetta; Raimondi, Maria Valeria; Raffa, Demetrio; Plescia, Fulvio; Cascioferro, Stella; Cancemi, Gabriella; Tolomeo, Manlio; Grimaudo, Stefania; Daidone, Giuseppe

doi:10.1016/j.ejmech.2015.04.004

Cited by 26 publications

(9 citation statements)

References 16 publications

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“…The latter effect is unsurprising, since the mentioned compounds with a chloromethyl substituent in the oxadiazole ring could become alkylating properties. This effect was also established for other heterocycles . So, the replacement of methyl substituent to 2‐chloroalkyl substituent in A‐ring of heterocyclic compounds such as tetrazepinones was highly detrimental for cytotoxic profile of the compounds.…”

Section: Resultsmentioning

confidence: 99%

“…This effect was also established for other heterocycles . So, the replacement of methyl substituent to 2‐chloroalkyl substituent in A‐ring of heterocyclic compounds such as tetrazepinones was highly detrimental for cytotoxic profile of the compounds. Evidently, chloroalkyl substituent when usually incorporated into a molecule generates a reactive alkylating intermediate more easily when compared to methyl or benzyl substituent.…”

Section: Resultsmentioning

confidence: 99%

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Furanolabdanoid–based 1,2,4‐oxadiazoles: Synthesis and cytotoxic activity

et al. 2016

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Several 15,16-epoxy-8,13,14-labdatriene derivatives modified at the C-16 position with a 1,2,4-oxadiazole ring with various substituent in the 5-th position, were obtained via multistep synthesis from 16-formyl derivatives of natural diterpenoid lambertianic acid. The cytotoxicity of furanolabdanoid-based 1,2,4oxadiazoles was evaluated against human cancer cells (CEM-13, MT-4, U-937, MCF-7, MDA-MB-231, MEL-8) using the conventional MTT assays. All the tested diterpenoid-oxadiazole hybrids displayed better cytotoxic activity then lambertianic acid. The activity and selectivity to the cell line increased even further in the compounds containing a chloromethyl substituent in the 5th position of the 1,2,4-oxadiazole ring. Two of the synthesized compounds exhibited high cytotoxic activity against lymphoblastoid cell line CEM-13 (GI 50 0.08-0.34 mM), which was higher that than of the comparative drug Doxorubicin. The antitumor mechanism may be related to apoptosis induction in U-937, MCF-7, and CEM-13 cells.[a] Dr.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Furanolabdanoid–based 1,2,4‐oxadiazoles: Synthesis and cytotoxic activity

et al. 2016

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“…Pentatomic nitrogenous heterocyclic compounds are widely described in the literature for a variety of biological activities [43][44][45] including the antibacterial activity [46][47][48]. This observation, combined with the interesting biological results observed with the natural pyrrolomycins, encouraged the synthesis of new analogs.…”

Section: Synthetic Pyrrolomycinsmentioning

confidence: 99%

Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

et al. 2015

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Abstract:The emergence of antibiotic resistance is currently considered one of the most important global health problem. The continuous onset of multidrug-resistant Gram-positive and Gram-negative bacterial strains limits the clinical efficacy of most of the marketed antibiotics. Therefore, there is an urgent need for new antibiotics. Pyrrolomycins are a class of biologically active compounds that exhibit a broad spectrum of biological activities, including antibacterial, antifungal, anthelmintic, antiproliferative, insecticidal, and acaricidal activities. In this review we focus on the antibacterial activity and antibiofilm activity of pyrrolomycins against Gram-positive and Gram-negative pathogens. Their efficacy, combined in some cases with a low toxicity, confers to these molecules a great potential for the development of new antimicrobial agents to face the antibiotic crisis.

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“…Compound 2 was the most active compound in this search with an IC50 equal to 7.5 nM [21]. In addition, the literature survey revealed that the pyrazole moiety represents an important pharmacophore in several anticancer active agents [22][23][24][25][26][27][28]. All these facts encouraged us to hybridize the pyrazolo [3,4-d] [29] with acetylacetone in acetic acid for 10 h, as shown in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

(3,5-Dimethylpyrazol-1-yl)-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl]methanone

Bakr

Mehany

2016

Molbank

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In an attempt to enhance cytotoxic activity of pyrazolo[3,4-d]pyrimidine core, we synthesized (3,5-dimethylpyrazol-1-yl)-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl]methanone (4) by reacting 4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)benzohydrazide (3) with acetylacetone. Antiproliferative activity of this compound was screened against breast (MCF-7), colon (HCT-116), and liver (HEPG-2) cancer cell lines. The tested compound exhibited cytotoxic activity with IC 50 = 5.00-32.52 µM. Moreover, inhibitory activity of this compound was evaluated against the epidermal growth factor receptor (EGFR), the fibroblast growth factor receptor (FGFR), the insulin receptor (IR), and the vascular endothelial growth factor receptor (VEGFR). This target compound showed potent inhibitory activity, especially against FGFR with IC 50 = 5.18 µM.

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Synthesis and antiproliferative activity of 3-(2-chloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one

Cited by 26 publications

References 16 publications

Furanolabdanoid–based 1,2,4‐oxadiazoles: Synthesis and cytotoxic activity

Furanolabdanoid–based 1,2,4‐oxadiazoles: Synthesis and cytotoxic activity

Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins

(3,5-Dimethylpyrazol-1-yl)-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl]methanone

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