title: 3-(Dipropylamino)-5-hydroxybenzofuro[2,3-f]quinazolin-1(2H)-one (DPA-HBFQ-1) plays an inhibitory role on breast cancer cell growth and progression.
abstract: A series of unknown 3-(alkyl(dialkyl)amino)benzofuro[2,3-f]quinazolin-1(2H)-ones 4-17 has been synthesized as new ellipticine analogs, in which the carbazole moiety and the pyridine ring were replaced by a dibenzofuran residue and a pyrimidine ring, respectively. The synthesis of these benzofuroquinazolinones 4-17 was performed in a simple one-pot reaction using 3-aminodibenzofuran or its 2-methoxy derivative, as starting materials. From 3-(dipropylamino)-5-methoxybenzofuro[2,3-f] quinazolin-1(2H)-one (13), we prepared 3-(dipropylamino)-5-hydroxybenzofuro[2,3-f]quinazolin-1(2H)-one (18), referred to as DPA-HBFQ-1. The cytotoxic activities of all the synthesized compounds, tested in different human breast cancer cell lines, revealed that DPA-HBFQ-1 was the most active compound. In particular, the latter was able to inhibit anchorage-dependent and -independent cell growth and to induce apoptosis in estrogen receptor alpha (ERα)-positive and -negative breast cancer cells. It did not affect proliferation and apoptotic responses in MCF-10A normal breast epithelial cells. The observed effects have been ascribed to an enhanced p21(Cip1/WAF1) expression in a p53-dependent manner of tumor suppressor and to a selective inhibition of human topoisomerase II. In addition, DPA-HBFQ-1 exerted growth inhibitory effects also in other cancer cell lines, even though with a lower cytotoxic activity. Our results indicate DPA-HBFQ-1 as a good candidate to be useful as cancer therapeutic agent, particularly for breast cancer.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Rizza
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Pellegrino
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Iacopetta
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy. Electronic address: s.sinicropi@unical.it.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Sinicropi
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258, FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen Cedex, France. Electronic address: sylvain.rault@unicaen.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258, FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen Cedex, France.
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Lancelot
authors.affiliation: Department of Chemistry, Faculty of Science, Assiut University, 71516 Assiut, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: El-Kashef
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258, FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen Cedex, France.
authors.forename: Aurelien
authors.initials: A
authors.lastname: Lesnard
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258, FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen Cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rochais
authors.affiliation: Université de Caen Basse-Normandie, Centre d'Etudes et de Recherche sur le Médicament de Normandie UPRES EA 4258, FR CNRS 3038 INC3M, Bd Becquerel, 14032 Caen Cedex, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dallemagne
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Saturnino
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giordano
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Catalano
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, Italy. Electronic address: sebastiano.ando@unical.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D052999:Quinazolinones / Q000737:chemistry / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C000610765:3-(dipropylamino)-5-hydroxybenzofuro(2,3-f)quinazolin-1(2H)-one; D000970:Antineoplastic Agents; D001572:Benzofurans; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D052999:Quinazolinones; C495901:TP53 protein, human; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen
keywords: 3-(Alkyl(dialkyl)amino)-benzofuro[2,3-f]quinazolin-1(2H)-one analogs; 3-(dipropylamino)-5-hydroxybenzofuro[2,3-f]quinazolin-1(2H)-one; Apoptosis; Dibenzofuran derivatives; One-pot reaction