485-23-4

Upstream product

• 92194-92-8 4-(chlorocarbonyl)-2-(3-methylbut-2-en-1-yl)phenyl acetate 
• 1476-53-5 sodium novobiocin 
• 56971-02-9 3-amino-4,7-dihydroxy-8-methyl-2H-chromen-2-one 
• 1138-41-6 4-hydroxy-3-prenylbenzoic acid 
• 303-81-1 novobiocin 
• 3780-29-8 4,7-dihydroxy-3-amino-8-methylcoumarin hydrochloride 

Downstream Products

• 1990-85-8 4-acetoxy-3-(3-methylbut-2-en-1-yl)benzoic acid 
• 3780-30-1 7-acetoxy-2,6-dimethyl-chromeno[3,4-d]oxazol-4-one 
• 1348829-25-3 C₂₅H₂₇NO₆ 

Relevant academic research and scientific papers

Novobiocin Enhances Polymyxin Activity by Stimulating Lipopolysaccharide Transport

Gram-negative bacteria are challenging to kill with antibiotics due to their impenetrable outer membrane containing lipopolysaccharide (LPS). The polymyxins, including colistin, are the drugs of last resort for treating Gram-negative infections. These drugs bind LPS and disrupt the outer membrane; however, their toxicity limits their usefulness. Polymyxin has been shown to synergize with many antibiotics including novobiocin, which inhibits DNA gyrase, by facilitating transport of these antibiotics across the outer membrane. Recently, we have shown that novobiocin not only inhibits DNA gyrase but also binds and stimulates LptB, the ATPase that powers LPS transport. Here, we report the synthesis of novobiocin derivatives that separate these two activities. One analog retains LptB-stimulatory activity but is unable to inhibit DNA gyrase. This analog, which is not toxic on its own, nevertheless enhances the lethality of polymyxin by binding LptB and stimulating LPS transport. Therefore, LPS transport agonism contributes substantially to novobiocin-polymyxin synergy. We also report other novobiocin analogs that inhibit DNA gyrase better than or equal to novobiocin, but bind better to LptB and therefore have even greater LptB stimulatory activity. These compounds are more potent than novobiocin when used in combination with polymyxin. Novobiocin analogs optimized for both gyrase inhibition and LPS transport agonism may allow the use of lower doses of polymyxin, increasing its efficacy and safety.

An artificial pathway to 3,4-dihydroxybenzoic acid allows generation of new aminocoumarin antibiotic recognized by catechol transporters of E. coli

An artificial operon was synthesized, consisting of the genes for chorismate pyruvate-lyase of E. coli and for 4-hydroxybenzoate 3-hydroxylase of Corynebacterium cyclohexanicum. This operon, directing the biosynthesis of 3,4-dihdroxybenzoate, was expressed in the heterologous expression host Streptomyces coelicolor M512, together with a modified biosynthetic gene cluster for the aminocoumarin antibiotic clorobiocin. The resulting strain produced a clorobiocin derivative containing a 3,4-dihdroxybenzoyl moiety. Its structure was confirmed by MS and NMR analysis, and it was found to be a potent inhibitor of the gyrases from Escherichia coli and Staphylococcus aureus. Bioassays against different E. coli mutants suggested that this compound is actively imported by catechol siderophore transporters in the cell envelope. This study provides an example of the structure of a natural product that can be rationally modified by synthetic biology.

HOMODIMERIC TOBRAMYCIN ADJUVANT REPURPOSES NOVOBIOCIN AS AN EFFECTIVE ANTIBACTERIAL AGENT AGAINST GRAM-NEGATIVE BACTERIA

Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the develo

Homodimeric Tobramycin Adjuvant Repurposes Novobiocin as an Effective Antibacterial Agent against Gram-Negative Bacteria

Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the develo

AUTOPHAGY INHIBITORS

A compound, which is a) a tetrahydrotriazine derivative of the formula (I), a tautomer, a pharmaceutically acceptable salt, a solvate or hydrate thereof, were the symbols have the meanings given in the description, or b) a coumarin derivative of the formula (II), a tautomer, a pharmaceutically acceptable salt, solvate or hydrate thereof, were the symbols have the meanings given in the description, is useful in a therapeutical method for inhibiting autophagy in a cell and for the treatment of cancer.

New novobiocin analogues as antiproliferative agents in breast cancer cells and potential inhibitors of heat shock protein 90

Selective hsp90 inhibitors simultaneously destabilize and deplete key signaling proteins involved in cell proliferation and survival, angiogenesis, and metastasis. Investigation of novobiocin analogues lacking the noviose moiety as novel inhibitors of hsp