Discovery and syntheses of "superbug challengers"-platensimycin and platencin.
Bacteria have developed resistance to almost all existing antibiotics known today and this has been a major issue over the last few decades. The search for a new class of antibiotics with a new mode of action to fight these multiply-drug-resistant strains, or "superbugs", allowed a team of scientists at Merck to discover two novel antibiotics, platensimycin and platencin using advanced screening strategies, as inhibitors of bacterial fatty acid biosynthesis, which is essential for the survival of bacteria. Though both these antibiotics are structurally related, they work by slightly different mechanisms and target different enzymes conserved in the bacterial fatty acid biosynthesis. This Focus Review summarizes the synthetic and biological aspects of these natural products and their analogues and congeners.
Palanichamy
Kalanidhi
K
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai-400 076, India.
Kaliappan
Krishna P
KP
D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D062365:Aminobenzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000627:Aminophenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial; D054872:Fatty Acid Synthesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D062365:Aminobenzoates; D000627:Aminophenols; D000813:Anilides; D000890:Anti-Infective Agents; D054872:Fatty Acid Synthesis Inhibitors; D011083:Polycyclic Compounds; D000218:Adamantane; C510909:platensimycin; C520340:platencin