Coumermycin A1 is a natural, broad-spectrum aminocoumarin and DNA gyrase inhibitor. Coumermycin A1 was developed in the early 1970s by Roche Applied Science. Coumarin glycosides are aromatic compounds containing a carbohydrate glycosidically bound to a coumarin and Coumermycin is structurally related to novobiocin. Coumermycin A1 has bacteriostatic activity against Gram-positive and Gam-negative bacteria. It also has activity against HIV-1.
Coumermycin A1 is soluble in DMSO.
| Mechanism of Action | Coumermycin A1 targets the B subunit of bacterial DNA gyrase, specifically gyrase B or gyrB, inhibiting the supercoiling activity and thus DNA synthesis. DNA gyrase belongs in the subclass Type IIA topoisomerase of the DNA topoisomerase II. |
| Spectrum | Coumermycin A1 has activity against Gram-positive (ie Staphylococcus) and Gram-negative bacteria. It also has activity against retroviruses including HIV-1. |
| Microbiology Applications |
Coumermycin A1 is often used to select for cells with a mutation in the gyrB gene which confers resistance to Coumermycin A1. Coumermycin A1 inhibited in vitro RNA synthesis by African Swine Flu (ASF) virus particles (Salas et al, 1983). Coumermycin A1 was found to inhibit human immunodeficiency virus type 1 (HIV-1) in vitro. Coumermycin A1, unlike other DNA gyrase inhibitors (novobiocin, nalidixic acid, and oxolinic acid) had inhibitory activity against HIV-1. EC50 for MT-4 cells was 1.5 µg/ml. Other DNA gyrase inhibitors studied (novobiocin, nalidixic acid and oxolinic acid) were devoid of any inhibitory activity against HIV-1 at 100 or 250 µg/ml (Baba, 1989). Coumermycin A1 was found to be a potent antiretroviral. It inhibited HIV-1 integration and gene expression but the two activities mapped to distinct targets, thus a ‘dual target’ antiretivoral. It prevented integration by targeting the capsid protein, and prevented gene expression by targeting heat shock protein (HSp90). (Vozzolo et al, 2010). |
| Molecular Formula | C55H59N5O20 |
| References |
Baba M et al (1989) Coumermycin A1 is a potent inhibitor of human immunodeficiency virus (HIV) replication in vitro. Int. J. Exp. Clin. Chemother. 2(1):15-20 Engle EC, Manes SH and Drlica K (1982). Differential effects of antibiotics inhibiting gyrase. J. Bacteriol. 149(1):92–98 PMID 6274849 Fedorko J, Katz S and Allnoch H (1969). In vitro activity of Coumermycin A1. Appl. Microbiol. 18(5):869–873 PMID 4391844 Salas ML, Kuznar J and Viñuela E (1983) Effect of rifamycin derivatives and Coumermycin A1 on in vitro RNA synthesis by African swine fever virus. Arch. Virol. 77:77–80 PMID 6625887 Samuels DS, Marconi RT, Huang WM and Garon CF 91994). GyrB mutations in coumermycin A1-resistant Borrelia burgdorferi. J. Bacteriol. 176(10):3072–3075 Vanden Broeck A, McEwen AG, Chebaro Y, Potier N, Lamour V (2019) Structural basis for DNA gyrase interaction with Coumermycin A1. J. Med. Chem. 62(8):4225–4231 PMID 30920824 Vozzolo L et al (2010) Gyrase B inhibitor impairs HIV-1 replication by targeting Hsp90 and the capsid protein. J. Biol. Chem. 285:39314-39328 |
