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Synthesis, antimycobacterial activity and docking study of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives and related hydrazide-hydrazones.
Angelova, Violina T; Valcheva, Violeta; Pencheva, Tania; Voynikov, Yulian; Vassilev, Nikolay; Mihaylova, Rositsa; Momekov, Georgi; Shivachev, Boris.
Afiliación
  • Angelova VT; Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria. Electronic address: violina@pharmfac.net.
  • Valcheva V; "Stefan Angelov" Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria.
  • Pencheva T; Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 105 Acad. G. Bonchev Str, 1113 Sofia, Bulgaria.
  • Voynikov Y; Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
  • Vassilev N; Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
  • Mihaylova R; Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
  • Momekov G; Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
  • Shivachev B; Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, 107 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria.
Bioorg Med Chem Lett ; 27(13): 2996-3002, 2017 07 01.
Article en En | MEDLINE | ID: mdl-28512022
A new convenient method for preparation of 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives 5b-g and coumarin containing hydrazide-hydrazone analogues 4a-e was presented. The antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and cytotoxicity against the human embryonic kidney cell line HEK-293 were tested in vitro. All compounds demonstrated significant minimum inhibitory concentrations (MIC) ranging 0.28-1.69µM, which were comparable to those of isoniazid. The cytotoxicity (IC50>200µM) to the "normal cell" model HEK-293T exhibited by 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives 5b-e, was noticeably milder compared to that of their hydrazone analogues 4a-e (IC50 33-403µM). Molecular docking studies on compounds 4a-e and 5b-g were also carried out to investigate their binding to the 2-trans-enoyl-ACP reductase (InhA) enzyme involved in M. tuberculosis cell wall biogenesis. The binding model suggested one or more hydrogen bonding and/or arene-H or arene-arene interactions between hydrazones or pyrazole-fused coumarin derivatives and InhA enzyme for all synthesized compounds.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazolonas / Simulación del Acoplamiento Molecular / Hidrazinas / Hidrazonas / Antibacterianos / Mycobacterium tuberculosis Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazolonas / Simulación del Acoplamiento Molecular / Hidrazinas / Hidrazonas / Antibacterianos / Mycobacterium tuberculosis Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido