Your browser doesn't support javascript.
loading
Benzoxazine derivatives of phytophenols show anti-plasmodial activity via sodium homeostasis disruption.
Sharma, Vijeta; Amarnath, Nagarjuna; Shukla, Swapnil; Ayana, R; Kumar, Naveen; Yadav, Nisha; Kannan, Deepika; Sehrawat, Seema; Pati, Soumya; Lochab, Bimlesh; Singh, Shailja.
Afiliación
  • Sharma V; Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: vs617@snu.edu.in.
  • Amarnath N; Department of Chemistry, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: nagarjuna.amarnath@snu.edu.in.
  • Shukla S; Department of Chemistry, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: ss771@snu.edu.in.
  • Ayana R; Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: ra295@snu.edu.in.
  • Kumar N; Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: nk710@snu.edu.in.
  • Yadav N; Department of Chemistry, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: ny345@snu.edu.in.
  • Kannan D; Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: dk929@snu.edu.in.
  • Sehrawat S; Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: Seema.Sehrawat@snu.edu.in.
  • Pati S; Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: soumya.pati@snu.edu.in.
  • Lochab B; Department of Chemistry, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India. Electronic address: bimlesh.lochab@snu.edu.in.
  • Singh S; Department of Life Sciences, Shiv Nadar University, Gautam Buddha Nagar UP, 201314, India; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: shailjasingh@mail.jnu.ac.in.
Bioorg Med Chem Lett ; 28(9): 1629-1637, 2018 05 15.
Article en En | MEDLINE | ID: mdl-29615339
Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na+ levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490 nM from 17.54 µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action.
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: Fenoles / Plasmodium falciparum / Sodio / Benzoxazinas / Homeostasis / Antimaláricos Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido
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: Fenoles / Plasmodium falciparum / Sodio / Benzoxazinas / Homeostasis / Antimaláricos Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido