title: Synthesis, Antiplatelet Activity and Cytotoxicity Assessment of Indole-Based Hydrazone Derivatives.
abstract: A series of indole-based aryl(aroyl)hydrazone analogs of antiplatelet indole-3-carboxaldehyde phenylhydrazone were synthesized by the Schiff base formation reaction and their antiplatelet activity was assessed using human platelet rich plasma. The platelet concentrate was obtained using a two-step centrifugation protocol and ADP, arachidonic acid and collagen were used as inducers of platelet aggregation. Based on the results, substituted phenylhydrazones showed promising activity. Among them, compound 1i was the most potent derivative with an IC50 comparable to that of indomethacin as a standard drug. The hydrazone derivatives were also tested for their cytotoxicity using on platelet concentrates and fibroblast L929 cells. The majority of the derivatives showed an acceptable selectivity towards antiplatelet aggregation activity. Based on the activity data, phenylhydrazone derivatives (1a-i) exhibited considerable antiplatelet activity and minimal toxic effect on platelet cells. The results of the present study could provide a better understanding of the structure activity relationship of antiplatelet indolehydrazones.
authors.affiliation: Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Kamaleddin
authors.initials: K
authors.lastname: Haj Mohammad Ebrahim Tehrani
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Esfahani Zadeh
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Vida
authors.initials: V
authors.lastname: Mashayekhi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Farzad
authors.initials: F
authors.lastname: Kobarfard
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Gharebaghi
authors.affiliation: Zanjan University of Medical Sciences, Zanjan, Iran ; Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Mohebbi
keywords: Antiplatelet aggregation; Arachidonic acid; Arylhydrazone; Collagen; Indole