title: Alkoxy and Enediyne Derivatives Containing 1,4-Benzoquinone Subunits-Synthesis and Antitumor Activity.
abstract: The compounds produced by a living organism are most commonly as medicinal agents and starting materials for the preparation of new semi-synthetic derivatives. One of the largest groups of natural compounds consists of products containing a 1,4-benzoquinone subunit. This fragment occurs in three enediyne antibiotics, dynemicin A, deoxydynemicin A, and uncilamicin, which exhibit high biological activity. A series of alkoxy derivatives containing 1,4-naphthoquinone, 5,8-quinolinedione, and 2-methyl-5,8-quinolinedione moieties was synthesized. Moreover, the 1,4-benzoquinone subunit was contacted with an enediyne fragment. All obtained compounds were characterized by spectroscopy and spectrometry methods. The resulting alkane, alkene, alkyne and enediyne derivatives were tested as antitumor agents. They showed high cytotoxic activity depending on the type of 1,4-benzoquinone subunit and the employed tumor cell lines. The synthesized derivatives fulfill the Lipinski Rule of Five and have low permeability through the blood-brain barrier.
authors.affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland. mkadela@sum.edu.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Kadela-Tomanek
authors.affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland. ebebenek@sum.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Bębenek
authors.affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland. echrobak@sum.edu.pl.
authors.forename: Elwira
authors.initials: E
authors.lastname: Chrobak
authors.affiliation: Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 8 Jedności Str., 41-200 Sosnowiec, Poland. mlatocha@sum.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Latocha
authors.affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland. boryczka@sum.edu.pl.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Boryczka
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D016227:Benzoquinones / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053281:Enediynes / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009285:Naphthoquinones / Q000737:chemistry; D009928:Organ Specificity; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D001688:Biological Products; D053281:Enediynes; D009285:Naphthoquinones; D011804:Quinolines; C512009:uncialamycin; C066107:deoxydynemicin A; C004532:quinone; C061229:dynemicin A; C035342:1,4-naphthoquinone
keywords: 1,4-benzoquinone; Lipinski Rule of Five; alkoxy substituent; antiproliferative activity; blood–brain barrier; enediyne