Healing compounds in scorpion venom: Stanford chemists have identified and synthesized two new healing compounds in scorpion venom that are effective at killing staph and tuberculosis bacteria in tissue samples and mice, highlighting the potential discoveries in the toxins of poisonous creatures.

The title of the post is a copy and paste from the title, subtitle, second and third paragraphs of the linked academic press release here:

Stanford researchers synthesize healing compounds in scorpion venom

Stanford chemists have identified and synthesized two new healing compounds in scorpion venom that are effective at killing staph and tuberculosis bacteria.

The team not only isolated the compounds in the scorpion’s venom, but also synthesized them in the lab and verified that the lab-made versions killed staphylococcus and drug-resistant tuberculosis bacteria in tissue samples and in mice.

The findings, published June 10 in the journal Proceedings of the National Academy of Sciences, highlight the potential pharmacological treasures awaiting discovery in the toxins of scorpions, snakes, snails and other poisonous creatures.

Journal Reference:

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

Edson Norberto Carcamo-Noriega, Shyam Sathyamoorthi, Shibdas Banerjee, Elumalai Gnanamani, Monserrat Mendoza-Trujillo, Dulce Mata-Espinosa, Rogelio Hernández-Pando, José Ignacio Veytia-Bucheli, Lourival D. Possani, Richard N. Zare

Proceedings of the National Academy of Sciences Jun 2019, 201812334;

Link: https://www.pnas.org/content/early/2019/06/06/1812334116

DOI: 10.1073/pnas.1812334116

Significance

Development of new drugs from the venom of dangerous animals (spiders, snakes, scorpions, snails) has recently attracted much chemotherapeutic interest. While most isolated and characterized venom components are found to be proteinic or peptidic in nature, here we report two 1,4-benzoquinone compounds, one red and another blue, derived from the venom of a rarely studied scorpion (Diplocentrus melici) indigenous to Mexico. After successful identification and synthesis of these compounds, the red and blue benzoquinones showed remarkable antimicrobial activities against Staphylococcus aureus and Mycobacterium tuberculosis, respectively. The observation that the blue compound is equally effective against normal and multidrug-resistant tuberculosis while appearing not to affect the epithelium of lungs heightens its potential as a new drug candidate.

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.

Leave a Reply

Your email address will not be published. Required fields are marked *