Scorpion venoms have potential therapeutic applications. They contain peptides and proteins that can block ion channels and modify cellular physiology. Specifically, bradykinin-potentiating peptides in venoms are similar to the hypertension drug Captopril. Venoms also contain novel antimicrobial peptides that can inhibit antibiotic-resistant bacteria. Certain non-disulfide bridged peptides show anti-cancer effects by disrupting cancer cell membranes more than normal cells. One such peptide, Chlorotoxin, binds specifically to brain cancer cells and may help deliver other drugs to tumors. Overall, the many uncharacterized compounds in scorpion venoms indicate their potential for developing new pharmaceuticals, especially as antibiotic resistance increases.

1. The Therapeutic
Potential of
Scorpion Venoms
Felix Churchill-Moss

2. Background
• Scorpion Oils used in early 20th century. To treat infections,
inflammatory conditions, tumors.
• In ancient Rome venoms used to diagnose smallpox, fever, leprosy
and wound healing.
• Scorpion venom toxins (SVTs)
o Short chain peptide – blocks K+ , Cl- ion channels.
o Long chain peptides – acts upon Na+, Ca2+ - most effective in humans

3. Structural characteristics
• Peptides, proteins, inorganic salts, heterocyclic compounds, free
amino chains.
• Disulphide bridged peptides (DBP)
o Modifies ion-channel permeability, major role in regulating cellular physiology
o conserved structure function
• Non-disulphide bridged peptides (NDBP)
o antimicrobial, anticancer, haemolytic, anti-inflammatory, immune-modulatory and bradykinin potentiating
activities.
o Multifunctional

4. Therapeutics
• Bradykinin potentiating activity.
o Venoms contain peptide with proline residues.
o Bradykinin responsible for vasodilation.
o The angiotensin converting enzyme (ACE) activates angiotensin I and angiotensin ii, but proteolytically
degrades Bradykinin – increased blood pressure
o Captopril (fig1) – ACE inhibitor – scorpion venom derived - hypertension
• New Alkaloid discovered
o The venom alkaloid ((Z)-N-(2-1H-imidazol-4-yl)ethyl)-3-(4-hydroxy-3-methoxyphenyl) (fig2) was the first
alkaloid to be isolated from the venom of the Mexican scorpion Megacormus gertshi. (fig 3)
o composed of histamine and vanillin moieties, pharmaceutical.
o alkaloid very similar structure to the hypotensive agent feruloylhistamine
o In vivo - non-insecticidal + non-toxic in animal models
fig1
fig3
fig2

5. Antimicrobial
• Search for new antibiotics that microorganisms aren't resistant to
• Venoms contain AMPs (antimicrobial peptides)
o Defense mechanism.
o Some AMPs can inhibit the growth against MRSA super bug.
• Cationic amphiphilic peptides –accumulation on bacteria. Lipoteichoic acid (LTA), lipopolysaccharides (LPS).
• Disrupts membrane/ pore formation – efflux of ions/nutrients changes – intracellular components leak.
• Venom AMPs similar to human defense AMP – signaling, rather than antimicrobial
• Imcroporin (17 amino acid AMP) - Isometrus maculates (fig4)
o potent antimicrobial activity against antibiotic-resistant microrganisms.
(MRCNS, MRSA and penicillin-resistant pneumococci)
o penicillin against MRSA. MIC 40 fold higher than incroporin
o High resistance to Gram-positive and Gram-negative bacteria
fig4

6. Anti-cancer
• Cationic alpha-helical peptides- anticancer peptides (ACPS)
o Small peptides, <50,
o net positive charge (+2 - +7)
o majority hydrophobic residues
• peptides fold into amphiphilic structures, contact with membranes.
• Cancer cells
o surface negative charge
o high levels of phosphophatidylerines/ o-glycosylated mucins. ACPs selectivity
o Levels of microvilli/ pseudopodia on transformed cancer cells.
o Tend to increase surface area of tumor cells. High [ACPs] on surface disrupting cellular structure.

7. Anti-cancer. Cont..
• Only 3 NDBP show anti-proliferative/ anticancer properties.
• Mauriporin – 48 amino acid residue – potent cytotoxic/antiproliferative activity
• IC50 4.4-7.8µM – prostate cancer lines.
• Necrotic mode of cell death – various receptors activated, cell membrane disrupted, apoptosis products released
extracellularly.
• Tumor marker
o Chlorotoxin (fig 5) – 36 amino aid peptide – (8 cysteines, 4 disulphide bonds). Blocks chloride channels
o Radiolabeled derivative of Chlorotoxin – specifically binds to glioma cells,
Conjugation of Cltx & the dye Cyc5.5 generates fluorescent derivative.
Aids surgery. (fig 6)
Drug carrier – carries drugs through un-permeable membranes (BBB), reach target.
CPP (cell penetrating peptides)
Androctonus Mauritanicus
fig5
fig6

8. Conclusion.
Career In Pharmaceutics.
• small fraction of venoms characterised. 1700+ species studied.
Endless exciting pharmaceutical possibilities.
• Pharmaceutical research – MIC, IC50, Test drugs effectiveness. Ion
channel research.
• LATOXAN – produces natural based active ingredients to aid drug
discovery (fig7)
• Natural product based – finding improvements and alternatives
on existing drugs. Aid drug discovery. (cancer drugs tends
towards natural products)
• Rising problem of antibiotic resistant microbials – find drugs
that can over come microbial resistance.
fig7