Indole trimers with antibacterial activity against Gram-positive organisms produced using combinatorial biocatalysis

McClay, Kevin; Mehboob, Shahila; Yu, Jerry; Santarsiero, Bernard D.; Deng, Jiangping; Cook, James L.; Jeong, Hyunyoung; Johnson, Michael E.; Steffan, Robert J.

doi:10.1186/s13568-015-0125-4

Indole trimers with antibacterial activity against Gram-positive organisms produced using combinatorial biocatalysis

Journal Article · Fri Jun 26 00:00:00 EDT 2015 · AMB Express

DOI:https://doi.org/10.1186/s13568-015-0125-4· OSTI ID:1597999

McClay, Kevin ^[1]; Mehboob, Shahila ^[2]; Yu, Jerry ^[2]; Santarsiero, Bernard D. ^[2]; Deng, Jiangping ^[3]; Cook, James L. ^[3]; Jeong, Hyunyoung ^[2]; Johnson, Michael E. ^[2]; Steffan, Robert J. ^[1]

CB&I Federal Services, Lawrenceville, NJ (United States)
Univ. of Illinois, Chicago, IL (United States)
Loyola Univ. Chicago, Maywood, IL (United States); Edward Hines Jr. VA Hospital, Hines, IL (United States)

The I100V isoform of toluene-4-monooxygenase was used to catalyze the oxidative polymerization of anthranil and various indoles under mildly acidic conditions, favoring the production of trimers. Compounds produced in sufficient yield were purified and tested for their ability to inhibit the growth of B. anthracis, E. faecalis, L. monocytogenes, S. aureus, and in some cases, F. tularensis. 15 of the compounds displayed promising antibacterial activity (MIC < 5 µg/ml) against one or more of the strains tested, with the best MIC values being <0.8 µg/ml. All of these compounds had good selectivity, showing minimal cytotoxicity towards HepG2 cells. The structure was solved for six of the compounds that could be crystallized, revealing that minimally two classes of indole based trimers were produced. One compound class produced was a group of substituted derivatives of the natural product 2,2-bis(3-indolyl) indoxyl. The other group of compounds identified was classified as tryptanthrin-like compounds, all having multi-ring pendant groups attached at position 11 of tryptanthrin. One compound of particular interest, SAB-J85, had a structure that suggests that any compound, with a ring structure that can be activated by an oxygenase, might serve as a substrate for combinatorial biocatalysis.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

OSTI ID:: 1597999

Journal Information:: AMB Express, Journal Name: AMB Express Journal Issue: 1 Vol. 5; ISSN 2191-0855

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
antibacterial
antibiotic resistance
combinatorial biocatalysis
drug discovery
indole
tryptanthrin

Indole trimers with antibacterial activity against Gram-positive organisms produced using combinatorial biocatalysis

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References (42)

Cited By (3)

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