title: A facile synthesis and microtubule-destabilizing properties of 4-(1H-benzo[d]imidazol-2-yl)-furazan-3-amines.
abstract: A series of 4-(1H-benzo[d]imidazol-2-yl)-furazan-3-amines (BIFAs) were prepared in good yields (60-90% for each reaction step) via a novel procedure from aminofurazanyl hydroximoyl chlorides and o-diaminobenzenes. The synthetic sequence was run under mild reaction conditions, it was robust and did not require extensive purification of intermediates or final products. Furthermore, there was no need for protection of reactive moieties allowing for the parallel synthesis of diverse BIFA derivatives. Subsequent biological evaluation of the resulting compounds revealed their anti-proliferative effects in the sea urchin embryo model and in cultured human cancer cell lines. The most active compounds showed 0.2-2 μM activities in both assay systems. The unsubstituted benzene ring of the benzoimidazole template as well as the unsubstituted amino group in the furazan ring were essential prerequisites for the antimitotic activity of BIFAs. Compound 57 bearing the 2-chlorophenyl acetamide substituent at the nitrogen atom of the imidazole ring was the most active molecule in the examined set.
authors.affiliation: Special Design and Construction Bureau SDCB "Technolog", 33-A Sovetskii Ave., Saint Petersburg 192076, Russian Federation. Electronic address: stepanoff@pisem.net.
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Stepanov
authors.affiliation: Special Design and Construction Bureau SDCB "Technolog", 33-A Sovetskii Ave., Saint Petersburg 192076, Russian Federation. Electronic address: astrchim@yandex.ru.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Astrat'ev
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: sab@ioc.ac.ru.
authors.forename: Aleksei B
authors.initials: AB
authors.lastname: Sheremetev
authors.affiliation: I. M. Sechenov First Moscow State Medical University, Trubetskaya Str. 8-2, 119991 Moscow, Russian Federation. Electronic address: mpcpr@yandex.ru.
authors.forename: Nataliya K
authors.initials: NK
authors.lastname: Lagutina
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: naduasha.85@mail.ru.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Palysaeva
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: tyurin@ioc.ac.ru.
authors.forename: Aleksei Yu
authors.initials: AY
authors.lastname: Tyurin
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: natali.aleksandrova.50@mail.ru.
authors.forename: Nataliya S
authors.initials: NS
authors.lastname: Aleksandrova
authors.affiliation: I. M. Sechenov First Moscow State Medical University, Trubetskaya Str. 8-2, 119991 Moscow, Russian Federation. Electronic address: cska76@gmail.com.
authors.forename: Nataliya P
authors.initials: NP
authors.lastname: Sadchikova
authors.affiliation: A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Str., 119991 Moscow, Russian Federation. Electronic address: kirshik@yahoo.com.
authors.forename: Kyrill Yu
authors.initials: KY
authors.lastname: Suponitsky
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: info@chemblock.com.
authors.forename: Olga P
authors.initials: OP
authors.lastname: Atamanenko
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: LeonidK@chemical-block.com.
authors.forename: Leonid D
authors.initials: LD
authors.lastname: Konyushkin
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: rs@chemical-block.com.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Semenov
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: sfirgang@yandex.ru.
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Firgang
authors.affiliation: Department of Biological and Medicinal Chemistry, Moscow Institute of Physics and Technology, Institutsky Per. 9, Dolgoprudny, Moscow Region 141700, Russian Federation. Electronic address: akiselyov@chemdiv.com.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Kiselyov
authors.affiliation: N. K. Kol'tsov Institute of Developmental Biology, RAS, Vavilov Str., 26, 119334 Moscow, Russian Federation. Electronic address: ms@chemical-block.com.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Semenova
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation. Electronic address: vs@zelinsky.ru.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Semenov
mesh_terms: D016475:3T3 Cells; D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012617:Sea Urchins / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D010069:Oxadiazoles
keywords: Benzoimidazolfurazanamines; Cytotoxicity; Inhibitors of tubulin polymerization; Sea urchin embryo