title: A new ibuprofen derivative inhibits platelet aggregation and ROS mediated platelet apoptosis.
abstract: Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs) and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.
authors.affiliation: DOS in Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Kodagahalli S
authors.initials: KS
authors.lastname: Rakesh
authors.affiliation: DOS in Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Swamy
authors.initials: S
authors.lastname: Jagadish
authors.affiliation: DOS in Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Ajjampura C
authors.initials: AC
authors.lastname: Vinayaka
authors.affiliation: DOS in Biochemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Mahadevappa
authors.initials: M
authors.lastname: Hemshekhar
authors.affiliation: DOS in Biochemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Paul
authors.affiliation: DOS in Biochemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Ram M
authors.initials: RM
authors.lastname: Thushara
authors.affiliation: DOS in Biochemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Mahalingam S
authors.initials: MS
authors.lastname: Sundaram
authors.affiliation: DOS in Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Toreshettahally R
authors.initials: TR
authors.lastname: Swaroop
authors.affiliation: DOS in Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Chakrabhavi D
authors.initials: CD
authors.lastname: Mohan
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Bangalore, India.
authors.lastname: Basappa
authors.affiliation: DOS in Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Marilinganadoddi P
authors.initials: MP
authors.lastname: Sadashiva
authors.affiliation: DOS in Biochemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Kempaiah
authors.initials: K
authors.lastname: Kemparaju
authors.affiliation: DOS in Biochemistry, University of Mysore, Manasagangotri, Mysore, India; Department of Studies and Research in Biochemistry, Tumkur University, Tumkur, India.
authors.forename: Kesturu S
authors.initials: KS
authors.lastname: Girish
authors.affiliation: DOS in Chemistry, University of Mysore, Manasagangotri, Mysore, India.
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007052:Ibuprofen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D007052:Ibuprofen