Your browser doesn't support javascript.
loading
Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells.
Sadovnikov, Kirill S; Vasilenko, Dmitry A; Gracheva, Yulia A; Zefirov, Nikolay A; Radchenko, Eugene V; Palyulin, Vladimir A; Grishin, Yuri K; Vasilichin, Vladislav A; Shtil, Alexander A; Shevtsov, Pavel N; Shevtsova, Elena F; Kuznetsova, Tamara S; Kuznetsov, Sergei A; Bunev, Alexander S; Zefirova, Olga N; Milaeva, Elena R; Averina, Elena B.
Afiliación
  • Sadovnikov KS; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Vasilenko DA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Gracheva YA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Zefirov NA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Radchenko EV; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Palyulin VA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Grishin YK; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Vasilichin VA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Shtil AA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Shevtsov PN; Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation.
  • Shevtsova EF; Institute of Physiologically Active Compounds, Chernogolovka MR, Russian Federation.
  • Kuznetsova TS; Institute of Physiologically Active Compounds, Chernogolovka MR, Russian Federation.
  • Kuznetsov SA; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Bunev AS; Institute of Biological Sciences, Cell Biology and Biosystems Technology, University of Rostock, Rostock, Germany.
  • Zefirova ON; Medicinal Chemistry Center, Togliatti State University, Togliatti, Russian Federation.
  • Milaeva ER; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Averina EB; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation.
Arch Pharm (Weinheim) ; 355(5): e2100425, 2022 May.
Article en En | MEDLINE | ID: mdl-35103336
A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin-targeting lead molecules with the acylated 4-aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of ß-aryl-substituted vinylketones by tert-butyl nitrite in the presence of water as a key step. 4-Methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5-trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3-methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1ab) to the androgen-sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI-26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antimitóticos / Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: Arch Pharm (Weinheim) Año: 2022 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antimitóticos / Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: Arch Pharm (Weinheim) Año: 2022 Tipo del documento: Article Pais de publicación: Alemania