title: Design and synthesis of isosteviol triazole conjugates for cancer therapy.
abstract: One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using "click" chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Ravil N
authors.initials: RN
authors.lastname: Khaybullin
authors.affiliation: Department of Radiation Oncology, College of Medicine, University of Florida Health Cancer Center, Gainesville, FL 32610, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Li
authors.affiliation: Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Katritzky
authors.affiliation: Department of Radiation Oncology, College of Medicine, University of Florida Health Cancer Center, Gainesville, FL 32610, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. xqi@cop.ufl.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D057930:Click Chemistry; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D045786:Diterpenes, Kaurane; D014230:Triazoles; C515747:isosteviol