Abstract
[(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), an organometallic derivative of the irreversible cyclooxygenase-1/2 (COX-1/2) inhibitor acetylsalicylic acid (ASS), demonstrated high growth-inhibitory potential against various tumor cell lines and inhibition of both COX isoenzymes. With the objective of increasing the selectivity for COX-2, we introduced a chlorine substituent in position 3, 4, 5, or 6 of the ASS moiety, respectively. Increased COX-2 selectivity is desirable as this isoenzyme is predominantly related to the development of cancer and abnormal tissue growth. The new compounds were investigated in comprehensive cellular biological assays to identify the impact of the chlorine substitution at the complex on COX-1/2 inhibition, antiproliferative activity, apoptosis, metabolic activity, cell-based COX inhibition, and cellular uptake. Chlorination distinctly reduced the effects at isolated COX-1 (about 25% inhibition at 10 μM; Co-ASS: 82.7%), while those at COX-2 remained almost unchanged (about 65% inhibition at 10 μM; Co-ASS: 78.5%). In cellular systems, with exception of the 6-Cl derivative, all compounds showed notable antitumor activity in COX-1/2 expressing tumor cells (HT-29 (IC50 = 1.5-2.7 μM), ...Continue Reading
References
May 7, 1976·Analytical Biochemistry·M M Bradford
Dec 22, 1998·Journal of Cancer Research and Clinical Oncology·R GustH Schönenberger
Nov 5, 1999·Trends in Pharmacological Sciences·L J Marnett, A S Kalgutkar
Dec 1, 1999·The Prostate·S GuptaH Mukhtar
Jan 24, 2002·The Journal of Pharmacology and Experimental Therapeutics·Burkhard Hinz, Kay Brune
Oct 3, 2002·British Journal of Haematology·Francis J GilesMaher Albitar
Mar 22, 2003·Acta Physiologica Scandinavica·T Yang
Nov 26, 2003·Progress in Lipid Research·Makoto Murakami, Ichiro Kudo
Aug 20, 2004·Pharmacological Reviews·Daniel L SimmonsTimothy Hla
Sep 4, 2004·Genome Biology·N V Chandrasekharan, Daniel L Simmons
Jan 22, 2005·Journal of Medicinal Chemistry·Ingo OttRonald Gust
Jun 28, 2005·Brain Research·Kenji KawaguchiSteven H Graham
Mar 8, 2007·Journal of Medicinal Chemistry·Anna L Blobaum, Lawrence J Marnett
Apr 5, 2007·ChemMedChem·Ingo OttRonald Gust
Oct 28, 2008·Journal of Lipid Research·Carol A Rouzer, Lawrence J Marnett
Dec 31, 2008·Angewandte Chemie·Ingo OttRonald Gust
Oct 1, 2009·The International Journal of Biochemistry & Cell Biology·Daniel F LeglerPetra Krause
Dec 8, 2009·Medicinal Research Reviews·Mohammed Naseer A Khan, Yong Sup Lee
Aug 3, 2010·The Veterinary Journal·Felisbina L QueirogaCarlos S Lopes
Aug 3, 2010·Breast Cancer Research and Treatment·Theodore M BraskyJo L Freudenheim
Oct 21, 2010·CA: a Cancer Journal for Clinicians·Fredika M RobertsonMassimo Cristofanilli
Sep 22, 2012·Seminars in Immunopathology·Masako Nakanishi, Daniel W Rosenberg
Sep 23, 2014·Gut·Peiwei LiYihua Wu
Jan 3, 2016·Drug Discovery Today·Miłosz RegulskiMarek Murias
Aug 30, 2016·European Journal of Medicinal Chemistry·Victoria ObermoserRonald Gust
Citations
Oct 21, 2018·Journal of Cellular Physiology·Nasser Hashemi GoradelKeywan Mortezaee
May 8, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Sirui LiBin Liu
Oct 17, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Daniel BaeckerRonald Gust
Jan 16, 2020·ChemPlusChem·Konrad Kowalski
Sep 19, 2020·Bioorganic Chemistry·Sina M HopffAram Prokop
Apr 28, 2021·Journal of Medicinal Chemistry·Alexandra K KnoxRonald Gust
Jul 31, 2021·Biological Trace Element Research·Kangping LiuJianzhu Liu
Nov 30, 2018·Chemical Reviews·Bernhard EnglingerWalter Berger
Dec 21, 2019·ACS Medicinal Chemistry Letters·Ting MengFu-Pei Liang
Nov 17, 2021·Journal of Medicinal Chemistry·Sandra Ramos-InzaDaniel Plano
Dec 12, 2021·Archiv der Pharmazie·Daniel BaeckerRonald Gust