title: Immunomodulatory properties of S- and N-alkylated 5-(1H-indol-2-yl)-1,3,4-oxadiazole-2(3H)-thione.
abstract: A series of S- and N-alkylated indolyloxadiazoles 2-7 were prepared. All compounds were tested for their immunomodulatory activity against T-cell proliferation, oxidative burst and cytokine analysis. Compounds 1, 2a, 2b, 2c and 2k demonstrated highly significant (P ≤ 0.005) inhibition on PHA activated T-cell proliferation with IC(50) less than 3 µg/mL concentration, while 3b exert a moderate inhibitory effect with IC(50) 8.6 µg/mL. Among all compounds of the series, only 2h was found to suppress phagocytes ROS production (IC(50) 2.4 µg/mL) in luminol-based chemiluminescence (CL) assay. Compounds 2a-k have stimulatory effect on proinflammatory cytokine predominantly IL-1β but no effect on IL-4 and NO production indicating that these compounds might have selective inhibitory effect on T-cell proliferation. Cytotoxic effect on T-cell proliferation was tested on NIH-3T3 mouse fibroblast normal cell line. All compounds were found to be free from toxic effects up to 100 μM concentration.
authors.affiliation: International Center for Chemical and Biological Sciences, H.E.J. Research Institute of Chemistry, Karachi University, Karachi, Pakistan. eelashry60@hotmail.com
authors.forename: El Sayed H
authors.initials: el SH
authors.lastname: El Ashry
authors.forename: El Sayed H
authors.initials: el SH
authors.lastname: El Tamany
authors.forename: Mohy El Din
authors.initials: Mel D
authors.lastname: Abd El Fattah
authors.forename: Mohamed R E
authors.initials: MR
authors.lastname: Aly
authors.forename: Ahmed T A
authors.initials: AT
authors.lastname: Boraei
authors.forename: M Ahmed
authors.initials: MA
authors.lastname: Mesaik
authors.forename: Omer M
authors.initials: OM
authors.lastname: Abdalla
authors.forename: Beenish
authors.initials: B
authors.lastname: Fatima
authors.forename: Almas
authors.initials: A
authors.lastname: Jabeen
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shukrulla
authors.forename: Samreen
authors.initials: S
authors.lastname: Soomro
mesh_terms: D000478:Alkylation; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D041681:NIH 3T3 Cells / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D007155:Immunologic Factors; D007211:Indoles; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D015847:Interleukin-4; D009569:Nitric Oxide