title: Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster.
abstract: Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR-13 and miR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species (ROS) level to trigger apoptotic cell death.
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IICT Campus, Hyderabad, India.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Mondal
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: A V S
authors.initials: AVS
authors.lastname: Lavanya
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: Akash
authors.initials: A
authors.lastname: Mallick
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: Tulshiram L
authors.initials: TL
authors.lastname: Dadmala
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
authors.forename: Ravindra M
authors.initials: RM
authors.lastname: Kumbhare
authors.affiliation: Functional Genomics and Gene silencing Group, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, 500007, India. utpal@ccmb.res.in.
authors.forename: Utpal
authors.initials: U
authors.lastname: Bhadra
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India. manikapb@gmail.com.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IICT Campus, Hyderabad, India. manikapb@gmail.com.
authors.forename: Manika Pal
authors.initials: MP
authors.lastname: Bhadra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001583:Benzoxazoles / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D038081:Organogenesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*; D014921:Wings, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D001583:Benzoxazoles; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D014230:Triazoles; D020169:Caspases
keywords: Apoptosis; Cancer; Micro RNA inhibitor; Small molecule