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In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold.
Kharbanda, Chetna; Alam, Mohammad Sarwar; Hamid, Hinna; Ali, Yakub; Nazreen, Syed; Dhulap, Abhijeet; Alam, Perwez; Pasha, M A Q.
Afiliación
  • Kharbanda C; Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110 062, India.
  • Alam MS; Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110 062, India. Electronic address: msalam@jamiahamdard.ac.in.
  • Hamid H; Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110 062, India. Electronic address: hhamid@jamiahamdard.ac.in.
  • Ali Y; Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110 062, India.
  • Nazreen S; Department of Chemistry, Faculty of Science, Albaha University, Saudi Arabia.
  • Dhulap A; CSIR Unit for Research and Development of Information Products, Pune 411038, India.
  • Alam P; Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, Delhi, India.
  • Pasha MAQ; Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, Delhi, India.
Bioorg Chem ; 106: 104458, 2021 01.
Article en En | MEDLINE | ID: mdl-33234295
Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site. Subsequently, all the derivatives were primarily deduced for their antidiabetic potential by OGTT. The compounds that showed significant antidiabetic activity in OGT Test and also exhibited high dock scores were assessed further by in vitro PPAR transactivation assay to assure analogy between in vivo and in vitro studies. The antidiabetic activity of these active compounds was then evaluated on STZ induced diabetic model in vivo. The most active compounds were scrutinized for its effect on PPAR-γ gene expression and hepatotoxic effect. Finally, it was recapitulated that these derivatives can provide a new prospect towards the development of antidiabetic agents with fewer side effects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilpropionatos / PPAR gamma / Diabetes Mellitus Experimental / Benzotiazoles / Hipoglucemiantes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Bioorg Chem Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilpropionatos / PPAR gamma / Diabetes Mellitus Experimental / Benzotiazoles / Hipoglucemiantes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Bioorg Chem Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos