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Repurposing of genistein as anti-sickling agent: elucidation by multi spectroscopic, thermophoresis, and molecular modeling techniques.
Syed, Muntjeeb M; Doshi, Pooja J; Bharshankh, Ankita; Dhavale, Dilip D; Kate, Sudam L; Kulkarni, Girish; Doshi, Jignesh B; Kulkarni, Mohan V.
Afiliación
  • Syed MM; Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Pune, Maharashtra, India.
  • Doshi PJ; Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Pune, Maharashtra, India.
  • Bharshankh A; Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Pune, Maharashtra, India.
  • Dhavale DD; Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Pune, Maharashtra, India.
  • Kate SL; Maharashtra Arogya Mandal's, Sumatibhai Shah Ayurved Ahavidyalaya - College of Ayurveda and Research Centre Hadapsar, Pune, Maharashtra, India.
  • Kulkarni G; Maharashtra Arogya Mandal's, Sumatibhai Shah Ayurved Ahavidyalaya - College of Ayurveda and Research Centre Hadapsar, Pune, Maharashtra, India.
  • Doshi JB; Toxoid Purification Department, Serum Institute of India Ltd, Hadapsar, Pune, Maharashtra, India.
  • Kulkarni MV; Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Pune, Maharashtra, India.
J Biomol Struct Dyn ; 40(9): 4038-4050, 2022 06.
Article en En | MEDLINE | ID: mdl-33305701
Sickle cell disease (SCD) is a major medical problem in which mono-therapeutic interventions have so far shown only limited effectiveness. We studied the repurpose of genistein, which could prevent sickle hemoglobin from polymerizing under hypoxic conditions in this disease. Genistein an important nutraceutical molecule found in soybean. The present study examines the repurposing genistein as an anti- sickling agent. Genistein shows inhibition of Hb S polymerization as well as a sickle reversal. Also, we have explored the interaction of the genistein with sickle hemoglobin (Hb S), using fluorescence, far-UV-CD spectroscopy, MicroScale Thermophoresis (MST), FTIR, combined with molecular modeling computations. The quenching constant decreases with increasing temperature, a characteristic that coincides with the static type of quenching mechanism. Temperature-dependent fluorescence measurements and molecular modeling studies reveal that apart from the hydrogen bonding, electrostatic interactions also play a crucial role in genistein and Hb S complex formation. In silico, distribution prediction of adsorption, digestion, metabolism, excretion, and toxicity (ADME/Tox) based on physical and chemical properties show that genistein is nontoxic and has ideal drug properties. The helicity and thermophoretic mobility of Hb S was a change in the presence of genistein, which leads to the destabilizing the Hb S polymer was examined using CD and MST, respectively. Our results open up the possibility for a promising therapeutic approach for the SCD by repurposed genistein as an anti-sickling agent.Communicated by Ramaswamy H. Sarma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemoglobina Falciforme / Anemia de Células Falciformes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Biomol Struct Dyn Año: 2022 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemoglobina Falciforme / Anemia de Células Falciformes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Biomol Struct Dyn Año: 2022 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido