Synthesis of isoindolo[1,4]benzoxazinone and isoindolo[1,5]benzoxazepine: two new ring systems of pharmaceutical interest

Parrino, Barbara; Ciancimino, Cristina; Carbone, Anna; Spanò, Virginia; Montalbano, Alessandra; Barraja, Paola; Cirrincione, Girolamo; Diana, Patrizia

doi:10.1016/j.tet.2015.04.083

Cited by 29 publications

(16 citation statements)

References 33 publications

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“…Continuing our search for new anticancer compounds [23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40], herein we report the synthesis of a new 1-methyl-3-[3-(1-methyl-1 H -indol-3-yl)-1,2,4-oxadiazol-5-yl]-1 H -pyrrolo[2,3- b ]pyridine nortopsentin analog 1 , designed on the basis of the potent activity shown by thiazole nortopsentin analogs with a 7-azaindole portion and considering the important characteristics of the 1,2,4-oxadiazole ring found in compounds with promising biological activity. The new compounds, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, and in which a 7-azaindole portion substituted the original indole, were prescreened against the HCT-116 colon rectal carcinoma cell line and the two most active compounds were selected and further investigated in different human tumor cell lines.…”

Section: Introductionmentioning

confidence: 99%

New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity

et al. 2019

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New analogs of nortopsentin, a natural 2,4-bis(3′-indolyl)imidazole alkaloid, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, and in which a 7-azaindole portion substituted the original indole moiety, were efficiently synthesized. Among all derivatives, prescreened against the HCT-116 colon rectal carcinoma cell line, the two most active compounds were selected and further investigated in different human tumor cells showing IC50 values in the micromolar and submicromolar range. Flow cytometric analysis of propidium iodide-stained MCF-7 cells demonstrated that both the active derivatives caused cell cycle arrest in the G0–G1 phase. The cell death mechanism induced by the compounds was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observed morphological evaluation using acridine orange/ethidium bromide double staining. Moreover, further tested on intestinal normal-like differentiated Caco-2 cell line, they exhibited preferential toxicity towards cancer cells.

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Section: Introductionmentioning

confidence: 99%

New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity

et al. 2019

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“…Continuing on our ongoing studies on nitrogen heterocyclic systems endowed with antitumor activity [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], and considering that hydrazide chains could improve the potency and pharmacokinetic properties of compounds bearing them [ 36 ], herein we report the synthesis of new 9 H -pyrido[2,3- b ]pyrrolizin-9-one tripentone analogs 9 , in which a pyridine replaces the thiophene ring of 8 H -thieno[2,3- b ]pyrrolizinones and in which different carbohydrazine chains were inserted with the aim of endowing them with the proper pharmacokinetic properties responsible for biological activity.…”

Section: Introductionmentioning

confidence: 99%

New Tripentone Analogs with Antiproliferative Activity

et al. 2017

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Tripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New tripentone analogs, in which a pyridine moiety replaces the thiophene ring originating the fused azaindole system endowed with anticancer activity viz 8H-thieno[2,3-b]pyrrolizinones, were efficiently synthesized in four steps with fair overall yields (34–57%). All tripentone derivatives were tested in the range of 0.1–100 μM for cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivative, with GI50 values of 4.25 µM and 20.73 µM for HCT-116 and MCF-7 cells, respectively, did not affect the viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of its cytotoxic action. The same compound was further investigated in order to study its mode of action. Results showed that it did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis. Flow cytometric analysis demonstrated that this compound caused cell cycle alteration, inhibiting its progression in S and G2/M phases.

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“…Benzoxazinone, which is a widely active heterocycle, 36,37 was combined with allylquinazolinone through molecular hybridization by Bollu et al 38 Pd-catalyzed Heck coupling was utilized in order to club 1,4-benzoxazinone and quinazolinone to produce novel 1,4-benzoxazinone-acetylphenylallylquinazolin-4(3H)-one hybrids. All the hybrids showed moderate to good anti-proliferative activity against 3 cancer cell lines (A549, HeLa, MDA-MB-231), with GI 50 in the range of 0.32-13.4 mM.…”

Section: Anti-cancer Hybridsmentioning

confidence: 99%