title: New indole-isoxazolone derivatives: Synthesis, characterisation and in vitro SIRT1 inhibition studies.
abstract: A new series of indole-isoxazolone hybrids bearing substituted amide, substituted [(1,2,3-triazol-4-yl)methoxy]methyl group or substituted benzylic ether at position-2 of the indole nucleus was synthesised using a facile synthetic route and the molecules were characterised using spectroscopic techniques. The molecules were screened against three human cancer cell lines to evaluate their in vitro cytotoxic property. Most of the trifluoromethyl substituted derivatives exhibited better growth inhibition activity than their methyl substituted analogues. The SIRT1 inhibition activity of two potent molecules (I17 and I18) was investigated and the SIRT1 IC50 values are 35.25 and 37.36 μM, respectively for I17 and I18. The molecular docking studies with SIRT1 enzyme revealed favourable interactions of the molecule I17 with the amino acids constituting the receptor enzyme.
authors.affiliation: Organic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasanagar, Mangalore 575025, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Panathur
authors.affiliation: Organic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasanagar, Mangalore 575025, India.
authors.forename: Nikhila
authors.initials: N
authors.lastname: Gokhale
authors.affiliation: Organic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasanagar, Mangalore 575025, India. Electronic address: udayaravi80@gmail.com.
authors.forename: Udayakumar
authors.initials: U
authors.lastname: Dalimba
authors.affiliation: Medicinal Chemistry and Drug Discovery Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Telengana 500078, India.
authors.forename: Pulla Venkat
authors.initials: PV
authors.lastname: Koushik
authors.affiliation: Medicinal Chemistry and Drug Discovery Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Telengana 500078, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Medicinal Chemistry and Drug Discovery Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Telengana 500078, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D057809:HEK293 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D007555:Isoxazoles / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D007211:Indoles; D007555:Isoxazoles; C030374:indole; D056564:Sirtuin 1
keywords: Click reaction; Indole; Isoxazolone; Molecular docking; SIRT1 inhibitors