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Design, synthesis, biological evaluation, and molecular modeling studies of rhodanine derivatives as pancreatic lipase inhibitors.
Chauhan, Divya; George, Ginson; Sridhar, S N C; Bhatia, Rohit; Paul, Atish T; Monga, Vikramdeep.
Afiliação
  • Chauhan D; Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, Moga, Punjab, India.
  • George G; Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science (Pilani campus), Pilani, Rajasthan, India.
  • Sridhar SNC; Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science (Pilani campus), Pilani, Rajasthan, India.
  • Bhatia R; Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, Moga, Punjab, India.
  • Paul AT; Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science (Pilani campus), Pilani, Rajasthan, India.
  • Monga V; Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, Moga, Punjab, India.
Arch Pharm (Weinheim) ; 352(10): e1900029, 2019 Oct.
Article em En | MEDLINE | ID: mdl-31407389
A series of rhodanine-3-acetic acid derivatives were synthesized via Knoevenagel condensation of rhodanine-3-acetic acid with various substituted aromatic aldehydes. The synthesized derivatives were screened in vitro for understanding the inhibitory potential towards pancreatic lipase (PL), a key enzyme responsible for the digestion of dietary fats. Derivative 8f exhibited a potential inhibitory activity towards PL (IC50 = 5.16 µM), comparable to that of the standard drug, orlistat (0.99 µM). An increase in the density of the aromatic ring resulted in potential PL inhibition. The enzyme kinetics of 8f exhibited a reversible competitive-type inhibition, similar to that of orlistat. Derivative 8f exhibited a MolDock score of -125.19 kcal/mol in docking studies, and the results were in accordance with their PL inhibitory potential. Furthermore, the reactive carbonyl group of 8f existed at a distance adjacent to Ser152 (≈3 Å) similar to that of orlistat. Molecular dynamics simulation (10 ns) of the 8f-PL complex revealed a stable binding conformation of 8f in the active site of PL (maximum root mean square displacement of ≈2.25 Å). The present study identified novel rhodanine-3-acetic acid derivatives with promising PL inhibitory potential, and further lead optimization might result in potent PL inhibitors.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pâncreas / Rodanina / Desenho de Fármacos / Inibidores Enzimáticos / Lipase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Arch Pharm (Weinheim) Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Índia

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pâncreas / Rodanina / Desenho de Fármacos / Inibidores Enzimáticos / Lipase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Arch Pharm (Weinheim) Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Índia