A paper published in PNAS  describes the characterization, synthesis and antimicrobial activity of two new benzoquinone compounds derived from the of the scorpion Diplocentus melici. The venom was extracted by electrical stimulation of the telson of D. melici and subsequent exposure to air caused the white venom to turn a dark red color.

    A combination of gel filtration on a sephadex column followed by reverse phase column chromatography yielded first the red compound and secondly the blue compound. The colors refer to the compounds in their dry powder form. Chemical analysis and subsequent synthesis provided the structures. Red on top and blue on the bottom.

    The compounds were tested first against Staphylococcus aureus. The minimum inhibitory concentration (MIC) for the red compound is 4 micrograms/mL and the MIC for the blue compound is 6 micrograms/mL. Ampicillin (MIC=0.5 micrograms/mL) was used as a positive control. Both compounds are bacteriocidal at their MICs killing 90% of S.aureus in 6 hours and 99.9% in 24 hours. Both compounds were then tested against Mycobacterium tuberculosis strains H37Rv and an MDR strain from clinical isolates. Only the blue compound showed significant inhibitory activity against both strains with a MIC of 4 micrograms/mL making it comparable in potency to drugs such as Isoniazid, Rifampicin and Levofloxacin. The blue compound was then tested against progressive pulmonary TB in infected mice. Eight micrograms of compound was administered by an intratracheal route every second day for two months. During this time treated mice showed no decrease in weight and no piloerection. The treated mice also showed a significant reduction of the lung bacillary load (>90%) compared to the untreated mice. Histologically the treated mice showed a two fold decrease in lung damage.

    The bacteriocidal activity of these compounds against S.aureus and the in vivo activity of the blue compound against Tuberculosis in mice are impressive to say the least. Hopefully further research including medicinal chemistry to further optimize the structures of these two lead compounds can produce a new class of antimicrobial drugs. Reference ttps://www.pnas.org/content/early/2019/06/06/1812334116