title: Biological and molecular docking studies on coagulin-H: Human IL-2 novel natural inhibitor.
abstract: Withanolide, coagulin-H (1), was evaluated for its effect on various cellular functions related to immune response including lymphocyte proliferation, and expression of interleukin-2 (IL-2) cytokine, and results were compared with prednisolone (2), a commonly used immune modulating drug. Coagulin-H (1) was found to have a powerful inhibitory effect on lymphocyte proliferation and Th-1 cytokine production. Inhibition of the phytohaemagglutinin (PHA)-activated T-cell proliferation by coagulin-H (1) was observed in a concentration dependent manner. A complete suppression of PHA-activated T-cell was observed at > or =2.5 microg/mL concentrations of compound (1) and this suppression activity was similar to that of prednisolone (2). Coagulin-H (1) also significantly inhibited IL-2 production by 80%. The interactions of coagulin-H (1) (a natural inhibitor) and prednisolone (2) (a drug) to IL-2 were also investigated in order to understand the differences in their effects on T-cell responses. This paper also describes the results of molecular docking study on IL-2 inhibition. Docking studies predicted that coagulin-H (1) binds to receptor binding site of IL-2 more effectively than prednisolone (2). Based on the computational and the experimental results, coagulin-H (1) was identified as a potential immunosuppressive candidate.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: M Ahmed
authors.initials: MA
authors.lastname: Mesaik
authors.lastname: Zaheer-Ul-Haq
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Murad
authors.forename: Zakiah
authors.initials: Z
authors.lastname: Ismail
authors.forename: Noor Rain
authors.initials: NR
authors.lastname: Abdullah
authors.forename: H Kauar
authors.initials: HK
authors.lastname: Gill
authors.lastname: Atta-Ur-Rahman
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yousaf
authors.forename: R Ali
authors.initials: RA
authors.lastname: Siddiqui
authors.forename: Aqeel
authors.initials: A
authors.lastname: Ahmad
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D008222:Lymphokines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008958:Models, Molecular; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010835:Phytohemagglutinins / Q000276:immunology; D011239:Prednisolone / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013925:Thromboplastin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D007376:Interleukin-2; D008222:Lymphokines; D010835:Phytohemagglutinins; C046147:interleukin 2 inhibitor; D004247:DNA; D013925:Thromboplastin; D011239:Prednisolone