Generation of methylated violapyrones with improved anti-influenza A virus activity by heterologous expression of a type III PKS gene in a marine Streptomyces strain

Bioorganic & Medicinal Chemistry Letters
Lukuan HouWenli Li

Abstract

Heterologous expression of the type III polyketide synthase (PKS) gene vioA in marine-derived Streptomyces youssoufiensis OUC6819 led to production of six violapyrones (VLPs), including four novel compounds VLPs Q-T (1-4) and two known compounds VLPs B and I (5 and 6). The structures of 1-4 were elucidated by a combination of spectroscopic analyses, including HR-ESIMS and 1D and 2D NMR data, demonstrating that 1-4 are novel VLPs which are methylated at 4-OH with their corresponding non-methylated counterparts to be VLP A, 5 and 6 and VLP C, respectively. Anti-influenza A [H1N1 (A/Virginia/ATCC1/2009) and H3N2 (A/Aichi/2/1968)] virus activity of compounds 1-6 as well as VLPs A and C were then evaluated using ribavirin as a positive control (IC50 = 66.7 and 99.6 μM). The results revealed that these VLPs showed considerable anti-H1N1 and anti-H3N2 activities with IC50 values of 30.6-132.4 μM and 45.3-150.0 μM, respectively. Notably, all the methylated VLPs displayed better anti-virus activity than their non-methylated counterparts, among which compound 3 (VLP S) exhibited the best activities. Interestingly, methylation at 4-OH has negative effect on the anti-MRSA (methicillin-resistant Staphylococcus aureus) activity instead, with...Continue Reading

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.