New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity
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 al...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/17/1/35 |
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| author | Stella Cascioferro Alessandro Attanzio Veronica Di Sarno Simona Musella Luisa Tesoriere Girolamo Cirrincione Patrizia Diana Barbara Parrino |
| author_facet | Stella Cascioferro Alessandro Attanzio Veronica Di Sarno Simona Musella Luisa Tesoriere Girolamo Cirrincione Patrizia Diana Barbara Parrino |
| author_sort | Stella Cascioferro |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T07:53:40Z |
| format | Article |
| id | doaj.art-7e316616b4b54c0f909e2d3cc5261766 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T07:53:40Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-7e316616b4b54c0f909e2d3cc52617662022-12-22T02:55:27ZengMDPI AGMarine Drugs1660-33972019-01-011713510.3390/md17010035md17010035New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic ActivityStella Cascioferro0Alessandro Attanzio1Veronica Di Sarno2Simona Musella3Luisa Tesoriere4Girolamo Cirrincione5Patrizia Diana6Barbara Parrino7Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, ItalyDepartment of Pharmacy, University of Salerno, Via G. Paolo II 132, 84084 Fisciano, ItalyDepartment of Pharmacy, University of Salerno, Via G. Paolo II 132, 84084 Fisciano, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, ItalyNew 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.http://www.mdpi.com/1660-3397/17/1/35marine alkaloidsnortopsentin analogs1,2,4-oxadiazole derivativesanti-cancer agentsantiproliferative activity |
| spellingShingle | Stella Cascioferro Alessandro Attanzio Veronica Di Sarno Simona Musella Luisa Tesoriere Girolamo Cirrincione Patrizia Diana Barbara Parrino New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity Marine Drugs marine alkaloids nortopsentin analogs 1,2,4-oxadiazole derivatives anti-cancer agents antiproliferative activity |
| title | New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity |
| title_full | New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity |
| title_fullStr | New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity |
| title_full_unstemmed | New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity |
| title_short | New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity |
| title_sort | new 1 2 4 oxadiazole nortopsentin derivatives with cytotoxic activity |
| topic | marine alkaloids nortopsentin analogs 1,2,4-oxadiazole derivatives anti-cancer agents antiproliferative activity |
| url | http://www.mdpi.com/1660-3397/17/1/35 |
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