The History of Gold Therapy for Tuberculosis

Abstract

This is a historical study of the popularization of a medical therapy contrary to pertinent experimental findings. Presumably this circumstance reflects the desperation about tuberculosis: highly prevalent, highly fatal, and lacking any etiologically directed therapy. Gold compounds were introduced, based initially on the reputation of Robert Koch, who had found gold cyanide effective against M. tuberculosis in cultures, but not in experimentally infected animals. Treatment of pulmonary tuberculosis with these compounds was popularized, particularly by Danish physicians, in the mid-1920s, despite consistently negative experimental results, based on Paul Ehrlich's theories of antimicrobial drug effects. Difficulties in the design of interpretable clinical studies were soon recognized but also generally ignored, thus permitting data to be interpreted as favorable to antituberculous gold therapy. Eventually toxicity was considered to outweigh the alleged therapeutic benefit of all gold compounds. This resulted in their discard shortly before the introduction of streptomycin therapy.

Auranofin and its Analogues Show Potent Antimicrobial Activity against Multidrug‐Resistant Pathogens: Structure–Activity Relationships

“…The liquid phase was evaporated to afford the pure product (380 mg, 77.8 %). 1 [Ag(PEt 3 )I].U nder inert conditions, AgI (260 mg) was added to a solution of PEt 3 in tetrahydrofuran (1 m, 0.9 mL, 0.8 equiv). The heterogeneous mixture was stirred at RT for 1.5 h, then the liquid phase was evaporated under reduced pressure.…”

“…For instance, the complex dicyanoaurate(I) was proposed andu sed by Koch as an antitubercular agent during the pioneering times of modernp harmacology, and severalb ismuth, antimony andm ercury compounds have been extensively used to combat variousb acterial and parasitic diseases. [1][2][3][4] However, more recently,d ue to the advent of the golden era of antibiotics ando wing to justified concerns about their systemic toxicity, metal-based agents have been gradually abandoned. Only af ew exceptions remain in the clinic for specific therapeutic indications, such as bis-muth salts for the eradication of Helicobacter pylori infection, and antimony compounds as antileishmanial agents.…”

Inhibition of 19S proteasome-associated deubiquitinases by metal-containing compounds

“…Gold also has a long history as a potent therapeutic agent [27-31]. Gold (I) compounds such as auranofin have been used clinically to treat rheumatoid arthritis for many years.…”

Gold(I) Analogues of a Platinum−Acridine Antitumor Agent Are Only Moderately Cytotoxic but Show Potent Activity against Mycobacterium tuberculosis

“…3 Gold(I)-based coordination compounds have been a major focus area in inorganic drug design since Robert Koch’s discovery of the bacteriostatic effects of dicyanoaurate(I), [Au(CN) 2 ] − . 4, 5 Complexes such as sodium bis(thiosulfato- S )aurate(I) (sanocrysin, Chart 1) have shown considerable promise as antimicrobial treatments for Mycobacterium tuberculosis (Mtb), the pathogen responsible for tuberculosis (TB). 4 However, the high systemic toxicity of this agent, the lack of a statistically significant antitubercular effect at tolerable doses, and shortcomings in the design and evaluation of early clinical trials resulted in a complete abandonment of Mtb-directed gold therapy.…”

“…4 However, the high systemic toxicity of this agent, the lack of a statistically significant antitubercular effect at tolerable doses, and shortcomings in the design and evaluation of early clinical trials resulted in a complete abandonment of Mtb-directed gold therapy. 4 On the other hand, the orally active drug triethylphosphine(2,3,4,6-tetra- O -acetyl- β -1-D-thiopyranosato- S )gold(I) (auranofin, Chart 1) has become an established second-line therapy in the treatment of severe rheumatoid arthritis and other autoimmune disorders. 6 Recently, several classes of gold(I) complexes have been reported that efficiently inhibit cancer cell growth, most likely by interfering with mitochondrial thioredoxin reductase (TrxR), suggesting possible applications of gold(I) in oncology.…”