title: Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (II).
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major problem, causing severe and intractable infections worldwide. MRSA is resistant to all beta-lactam antibiotics, and alternative treatments are limited. A very limited number of new antibiotics have been discovered over the last half-century, novel agents for the treatment of MRSA infections are urgently needed. Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008. After we reported the first total synthesis of (±)-marinopyrrole A, we designed and synthesized a series of marinopyrrole derivatives. Our structure activity relationship (SAR) studies of these novel derivatives against a panel of Gram-positive pathogens in antibacterial assays have revealed that a para-trifluoromethyl analog (33) of marinopyrrole A is ≥ 63-, 8-, and 4-fold more potent than vancomycin against methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA, respectively. The results provide valuable information in the search for new-generation antibiotics.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, Department of Medicinal Natural Products, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. chengchunwei666@163.com
authors: Chunwei
authors: C
authors: Cheng
authors: Yan
authors: Y
authors: Liu
authors: Hao
authors: H
authors: Song
authors: Lili
authors: L
authors: Pan
authors: Jerry
authors: J
authors: Li
authors: Yong
authors: Y
authors: Qin
authors: Rongshi
authors: R
authors: Li
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011758:Pyrroles; C528298:marinopyrrole A; D014640:Vancomycin
references: J Comb Chem. 2010 Jul 12;12(4):541-7
references: 20429575
references: J Org Chem. 2010 May 21;75(10):3240-50
references: 20405892
references: Chem Commun (Camb). 2013 Jan 21;49(6):558-60
references: 23128288
references: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references: 11259830
references: J Pharm Sci. 1997 Jul;86(7):865-71
references: 9232530
references: J Am Chem Soc. 2002 Jun 5;124(22):6421-7
references: 12033873
references: Expert Opin Investig Drugs. 2004 Sep;13(9):1159-69
references: 15330747
references: Lancet. 2006 Sep 2;368(9538):874-85
references: 16950365
references: Public Health Rep. 2009 May-Jun;124(3):427-35
references: 19445419
references: Mar Drugs. 2012 Apr;10(4):953-62
references: 22690153
references: Org Lett. 2010 Nov 5;12(21):4872-5
references: 20886840
references: Lancet. 2010 May 1;375(9725):1557-68
references: 20206987
references: J Clin Invest. 2003 May;111(9):1265-73
references: 12727914
references: J Am Chem Soc. 2012 Aug 1;134(30):12434-7
references: 22800473
references: Org Lett. 2008 Feb 21;10(4):629-31
references: 18205372
references: Tetrahedron Lett. 2011 Apr 27;52(17):2041-2043
references: 21499535
references: Nat Rev Microbiol. 2009 Sep;7(9):629-41
references: 19680247
references: Biochem Pharmacol. 2006 Mar 30;71(7):919-29
references: 16289393
references: J Med Chem. 2010 Mar 25;53(6):2601-11
references: 20175530