1,4-Benzoquinone antimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom.

Abstract:

:Two 1,4-benzoquinone derivatives, found in the venom of the scorpion Diplocentrus melici following exposure to air, have been isolated, characterized, synthesized, and assessed for antimicrobial activities. Initially a white, viscous liquid, the extracted venom colors within minutes under ambient conditions. From this colored mixture, two compounds, one red, the other blue, were isolated and purified using chromatography. After a variety of NMR and mass spectrometry experiments, the red compound was determined to be 3,5- dimethoxy-2-(methylthio)cyclohexa-2,5-diene-1,4-dione, and the blue compound was determined to be 5-methoxy-2,3- bis(methylthio)cyclohexa-2,5-diene-1,4-dione. Because extremely small amounts of these compounds were isolated from the scorpion venom, we developed laboratory syntheses from commercially available precursors, allowing us to produce sufficient quantities for crystallization and biological assays. The red benzoquinone is effective against Staphylococcus aureus [minimum inhibitory concentration (MIC) = 4 µg/mL], while the blue benzoquinone is active against Mycobacterium tuberculosis (MIC = 4 µg/mL) and even against a multidrug-resistant (MDR) strain with nearly equal effectiveness. The bactericidal effects of both benzoquinones show comparable activity to commercially available antibiotics used against these pathogens and were cytotoxic to neoplastic cell lines, suggesting their potential as lead compounds for the development of novel antimicrobial and anticancer drugs. Importantly, the blue benzoquinone was also effective in vivo with mouse models of MDR tuberculosis infection. After treatment for 2 mo, four mice with late-stage active MDR tuberculosis had a significant decrease in pulmonary bacillary loads and tissue damage. Healthy mice served as negative controls and tolerated treatment well, without adverse side effects.

authors

Carcamo-Noriega EN,Sathyamoorthi S,Banerjee S,Gnanamani E,Mendoza-Trujillo M,Mata-Espinosa D,Hernández-Pando R,Veytia-Bucheli JI,Possani LD,Zare RN

doi

10.1073/pnas.1812334116

subject

Has Abstract

pub_date

2019-06-25 00:00:00

pages

12642-12647

issue

26

eissn

0027-8424

issn

1091-6490

pii

1812334116

journal_volume

116

pub_type

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