title: Monoterpene indole alkaloid hydrazone derivatives with apoptosis inducing activity in human HCT116 colon and HepG2 liver carcinoma cells.
abstract: The derivatization of dregamine (1) and tabernaemontanine (2), two epimeric monoterpene indole alkaloids isolated from the methanol extract of the roots of Tabernaemontana elegans, with several hydrazines and hydroxylamine gave rise to ten new derivatives (3-12). Their structures were assigned by spectroscopic methods, including 2D NMR experiments. The compounds were tested for their ability to induce apoptosis in HCT116 colon and HepG2 liver cancer cells. Firstly, the cytotoxicity of all compounds (1-12) was evaluated in both cell lines by the MTS assay. The most active compounds (6, 9, 10) along with 1 and 2 were further investigated for their apoptosis induction capability by Guava ViaCount flow cytometry assays, nuclear morphology evaluation by Hoechst staining, and caspase-3/7 activity assays. Compounds 9 and 10 showed promising apoptosis induction profile, displaying higher activities than 5-fluorouracil, the mainstay in colon cancer treatment.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Angela
authors.initials: A
authors.lastname: Paterna
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Borralho
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Sofia E
authors.initials: SE
authors.lastname: Gomes
authors.affiliation: Centro de Estudos Moçambicanos e de Etnociências (CEMEC), Faculdade de Ciências Naturais e Matemática, Universidade Pedagógica Campus de Lhanguene, Av. de Moçambique, 21402161 Maputo, Mozambique.
authors.forename: Silva
authors.initials: S
authors.lastname: Mulhovo
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: mjuferreira@ff.ulisboa.pt.
authors.forename: Maria-José U
authors.initials: MJ
authors.lastname: Ferreira
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D018517:Plant Roots / Q000737:chemistry; D030014:Tabernaemontana / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006835:Hydrazones; D026121:Indole Alkaloids
keywords: Apoptosis; Hydrazones; Monoterpene indole alkaloids; Tabernaemontana elegans