title: Synthesis, isomerization and biological activity of novel 2-selenohydantoin derivatives.
abstract: A set of novel selenohydantoins were synthesized via a convenient and versatile approach involving the reaction of isoselenocyanates with various amines. We also revealed an unexpected Z→E isomerization of pyridin-2-yl-substituted selenohydantoins in the presence of Cu(2+) cations. The detailed mechanism of this transformation was suggested on the basis of quantum-chemical calculations, and the key role of Cu(2+) was elucidated. The obtained compounds were subsequently evaluated against a panel of different cancer cell lines. As a result, several molecules were identified as promising micromolar hits with good selectivity index. Instead of analogous thiohydantoins, which have been synthesized previously, selenohydantoins demonstrated a relatively high antioxidant activity comparable (or greater) to the reference molecule, Ebselen, a clinically approved drug candidate. The most active compounds have been selected for further biological trials.
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation; National University of Science and Technology MISiS, Moscow 119049, Russian Federation; Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russian Federation. Electronic address: yai@chemdiv.com.
authors.forename: Yan A
authors.initials: YA
authors.lastname: Ivanenkov
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russian Federation. Electronic address: vms@pharmcluster.ru.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Veselov
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russian Federation.
authors.forename: Igor G
authors.initials: IG
authors.lastname: Rezekin
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Dmitriy A
authors.initials: DA
authors.lastname: Skvortsov
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russian Federation.
authors.forename: Yuri B
authors.initials: YB
authors.lastname: Sandulenko
authors.affiliation: Moscow Institute of Physics and Technology (MIPT), Dolgoprudny, InstitutskiPereulok 9, Moskovskaya Oblast, Russian Federation.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Polyakova
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Dmitry S
authors.initials: DS
authors.lastname: Bezrukov
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Vasilevsky
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Maxim E
authors.initials: ME
authors.lastname: Kukushkin
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Moiseeva
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Finko
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Koteliansky
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation; National University of Science and Technology MISiS, Moscow 119049, Russian Federation.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Lubov A
authors.initials: LA
authors.lastname: Filatova
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation; National University of Science and Technology MISiS, Moscow 119049, Russian Federation.
authors.forename: Elena K
authors.initials: EK
authors.lastname: Beloglazkina
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Zyk
authors.affiliation: Moscow State University, Chemistry Dept., 119991 Moscow, Leninskie Gory, Building 1/3, GSP-1, Russian Federation; National University of Science and Technology MISiS, Moscow 119049, Russian Federation. Electronic address: majouga@org.chem.msu.ru.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Majouga
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D003485:Cyanates / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001393:Azoles; D003485:Cyanates; D006827:Hydantoins; D054833:Isoindoles; D016566:Organoselenium Compounds; D011725:Pyridines; C042986:ebselen; D003300:Copper; D005979:Glutathione Peroxidase
keywords: Anticancer activity; Antioxidant activity; Complexation; Electrochemistry; Isomerization; Quantum-chemical study; Selenohydantoin