Abstract
Thirty one ent-kaurane derivatives were prepared from kaurenoic acid (1), grandiflorenic acid (16), 15alpha-acetoxy-kaurenoic acid (26) and 16alpha-hydroxy-kaurenoic acid (31). They were tested for their ability to inhibit cell viability in the mouse leukemic macrophagic RAW 264.7 cell line. The most effective compounds were 12, 20, 21, and 23. These were selected for further evaluation in other human cancer cell lines such as Hela, HepG2, and HT-29. Similar effects were obtained although RAW 264.7 cells were more sensitive. In addition, these compounds were significantly less cytotoxic in non-transformed cells. The apoptotic potential of the most active compounds was investigated and they were able to induce apoptosis with compound 12 being the best inducer. The caspase-3, -8 and -9 activities were measured. The results obtained showed that compounds 12, 21, and 23 induce apoptosis via the activation of caspase-8, whereas compound 20 induces apoptosis via caspase-9. Immunoblot analysis of the expression of p53, Bax, Bcl-2, Bcl-xl, and IAPs in RAW 264.7 cells was also carried out. When cells were exposed to 5 microM of the different compounds, expression levels of p53 and Bax increased whereas levels of antiapoptotic proteins s...Continue Reading
References
Apr 25, 1996·Nature·M EnariS Nagata
Sep 4, 1998·Cell·H LiJ Yuan
Dec 5, 1998·The Journal of Biological Chemistry·G LyssI Merfort
Dec 1, 1999·Cell Death and Differentiation·D W Nicholson
Dec 1, 1999·Cell Death and Differentiation·E A SleeS J Martin
Dec 28, 1999·Trends in Cell Biology·Z Song, H Steller
Oct 25, 2000·Journal of Chemical Information and Computer Sciences·D D Ridley
Mar 22, 2003·Phytochemistry·Ammanamanchi S R Anjaneyulu, Vadali Lakshmana Rao
Apr 28, 2004·Phytochemistry·Wei XiangHan-Dong Sun
Jun 17, 2006·Phytochemistry·Xian LiHandong Sun
Jun 19, 2007·Phytochemistry·James D McChesneyJohn T Henri
Sep 18, 2007·Phytochemistry·Yarimar RuizIván Galindo-Castro
Jan 15, 2008·Toxicology and Applied Pharmacology·Natalia GirónBeatriz de las Heras
Jun 3, 2008·Cellular and Molecular Life Sciences : CMLS·A SalminenJ Huuskonen
Jul 19, 2008·Breast Cancer Research and Treatment·Thangaiyan Rabi, Anupam Bishayee
Aug 12, 2008·Drug Discovery Today·Alan L Harvey
Citations
Jan 29, 2013·European Journal of Medicinal Chemistry·Ronan BatistaAlaíde B de Oliveira
Jan 7, 2014·Biological & Pharmaceutical Bulletin·Mina LeeSang Hyun Sung
Apr 25, 2013·Genetics and Molecular Research : GMR·V C FernandesA L Fachin
Oct 13, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Priscilla M MatosVladimir C G Heleno
Apr 9, 2013·Drug and Chemical Toxicology·Rakibe Beklem BostancıoğluAyse Tansu Koparal
May 14, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Majid MahdaviAlireza Foroumadi
Oct 31, 2015·Journal of Natural Products·Celia Bustos-BritoLeovigildo Quijano
Apr 22, 2015·Bioorganic & Medicinal Chemistry·Katiuska ChávezAlírica I Suárez
Mar 22, 2014·Natural Product Research·Y RuanX L Wang
Feb 19, 2013·Chemistry & Biodiversity·Motohiko UkiyaToshihiro Akihisa
Nov 24, 2018·Natural Product Reports·Yan LiuSheng-Hong Li
Nov 20, 2018·Anti-cancer Agents in Medicinal Chemistry·Élida B V S CavalcantiMarcus T Scotti
Aug 31, 2019·Chemistry & Biodiversity·Yan XiaYinping Zhao
Mar 15, 2019·Anti-cancer Agents in Medicinal Chemistry·Arezoo RahimianHojjatollah Nozad Charoudeh
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elena PruteanuVeaceslav Kulcițki