title: Concise total synthesis of water soluble metatacarboline A, C, D, E and F and its anticancer activity.
abstract: The simple, concise, protecting group free and first total synthesis of Metatacarboline alkaloids (abbreviated as Mc) Mc A, C, D, E and F are reported. The core structure of metatacarboline alkaloids has been constructed by the classical Wittig reaction as key step from easily accessible starting materials with 40-75% overall yields. These synthesized compounds have been subjected to evaluate for their anticancer activity using C6 glioma cell lines. Mc D and Mc F showed significant antiproliferative activity, which was confirmed by MTT and Clonogenic assay. FACS analysis showed that Mc D and Mc F arrested the cell cycle at sub G0/G1 and G2/M phase of cell cycle respectively. Further, Western blot analysis and immunohistochemistry of Mc D treated cells revealed activation of caspase dependent downstream signaling which led to apoptosis.
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.
authors.forename: Badher
authors.initials: B
authors.lastname: Naveen
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500 046, India; Department of Biotechnology & Bioinformatics, School of Life Sciences, University of Hyderabad, 500 046, India.
authors.forename: Anwita
authors.initials: A
authors.lastname: Mudiraj
authors.affiliation: Department of Biotechnology & Bioinformatics, School of Life Sciences, University of Hyderabad, 500 046, India.
authors.forename: Geeviman
authors.initials: G
authors.lastname: Khamushavalli
authors.affiliation: Department of Biotechnology & Bioinformatics, School of Life Sciences, University of Hyderabad, 500 046, India.
authors.forename: Phanithi Prakash
authors.initials: PP
authors.lastname: Babu
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500 046, India. Electronic address: rnsc@uohyd.ernet.in.
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Nagarajan
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D014867:Water
keywords: Antiproliferative activity; Apoptosis; Glioma cell lines; Metatacarboline alkaloids; Natural products; Total synthesis; Wittig reaction