3-Acetyl analogues of thiolactomycin, a thiotetronic acid natural product, were synthesized and profiled against livestock pathogens. Some analogues showed improved activity over thiolactomycin against Staphylococcus aureus and comparable activity against Pasteurella multocida. Several semisynthetically modified analogues of thiolactomycin showed no improvement in activity over thiolactomycin.
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http://dx.doi.org/10.1016/s0960-894x(01)00567-4 | DOI Listing |
Turk J Pharm Sci
October 2020
Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra.
Antimicrobial resistance (AMR) is the phenomenon developed by microorganism on exposure to antimicrobial agents, making them unresponsive. Development of microbial confrontation is a severe rising risk to global community well-being as treatment in addition, management of such resistant microbial infections is difficult and challenging. The situation requires action across all government sectors and society.
View Article and Find Full Text PDFAntibiotics (Basel)
August 2020
Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal By-Pass Road, Bhauri, Bhopal 462 066, Madhya Pradesh, India.
In the present investigation, the parent compound 4-amino-5-(4-fluoro-3-phenoxyphenyl)-4-1,2,4-triazole-3-thiol () and its Schiff bases , , and were subjected to whole-cell anti-TB against H37Rv and multi-drug-resistant (MDR) strains of (MTB) by resazurin microtiter assay (REMA) plate method. Test compound exhibited promising anti-TB activity against H37Rv and MDR strains of MTB at 5.5 µg/mL and 11 µg/mL, respectively.
View Article and Find Full Text PDFOrg Biomol Chem
March 2019
Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.
Thiotetronate-containing natural products, including thiolactomycin, thiotetromycin, and thiotetroamide, are potent, broad-spectrum antibacterial compounds that target fatty acid synthesis in bacteria. Natural modifications at the C-5 dialkyl position in this molecular series result in pronounced bioactivity differences. The C-5 acetamide-containing thiotetroamide, which is the more potent antibacterial agent in this family, is biosynthesized from the C-5 ethyl analogue thiotetromycin via a unique two-enzyme process involving the cytochrome P450-amidotransferase enzyme pair TtmP-TtmN.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) is the second important cause of death worldwide caused by a bacterium called . There is a need to find and develop new Anti-TB medications that are effective, inexpensive and suitable with human immunodeficiency virus and other anti-TB drugs used in many countries and mainly the developing countries where the disease is widespread. These drugs must be designed to shorten treatment time and to be active against resistant forms of the mycobacteria that will help to increase the patients compliance.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2017
Center of Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0204, USA.
The selective activation of unreactive hydrocarbons by biosynthetic enzymes has inspired new synthetic methods in C-H bond activation. Herein, we report the unprecedented two-step biosynthetic conversion of thiotetromycin to thiotetroamide C involving the tandem oxidation and amidation of an unreactive ethyl group. We detail the genetic and biochemical basis for the terminal amidation in thiotetroamide C biosynthesis, which involves a uniquely adapted cytochrome P450-amidotransferase enzyme pair and highlights the first oxidation-amidation enzymatic cascade reaction leading to the selective formation of a primary amide group from a chemically inert alkyl group.
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