Different roads to discovery; Prontosil (hence sulfa drugs) and penicillin (hence β-lactams)

Abstract

The important chemotherapeutic agents, Prontosil and pentenylpenicillin (penicillin F), were investigated initially by two men, Domagk and Fleming, who had been influenced by the horrendous wound infections of World War I. The very different pathways leading to their development and to that of the successor antibacterials (sulfa drugs, further penicillins, semi-synthetic penicillins), including the role played by patents, are discussed.

Prodrugs—from Serendipity to Rational Design

“…However, prontosil was not intentionally developed as a prodrug, because only later in the same year was it found to release an active agent, para-aminophenylsulfonamide, by reductive enzymes. The launch of prontosil gave rise to the second generation of sulfonamide prodrugs, because the sulfanilamide moiety was easy to link to other molecules (Bentley, 2009). In a similar way, Roche discovered the prodrug activity of the antituberculosis drug isoniazid more than 40 years after its introduction in 1952.…”

Infection prevention and control and the role of medical textiles

“…It was to be ten years later that work by Howard Florey and Ernst Chain in Oxford would solve the problem of obtaining suffi cient quantities of the new drug that allowed the successful testing of its antibacterial properties in mice infected with a lethal dose of streptococci in 1940. Production was scaled up in Oxford to obtain the even larger amounts of penicillin required for a clinical trial in patients, although perhaps surprisingly by this time a decision had been taken not to patent this new drug, as desired by Chain, who was informed by the Medical Research Council that 'the patenting of drugs was unethical and contrary to the traditions of medical research in Britain' (Bentley, 2009). Florey travelled to the USA to enlist their help with increasing the availability of penicillin.…”

Coordenação de metais a antibióticos como uma estratégia de combate à resistência bacteriana

“…38 Com relação às propriedades bio- lógicas exibidas pelos complexos metálicos contendo tetraciclinas, as pesquisas indicam que estes compostos são bons pontos de partida no que se refere ao desenvolvimento de novos agentes antitumorais e antimicrobianos. 39 Mais recentemente, compostos de coordenação contendo sulfonamidas como ligantes têm atraído a atenção, devido ao fato de que muitos deles têm demonstrado maior atividade antibacteriana do que as drogas livres. Além disso, existe no mercado um complexo de prata contendo a sulfadiazina, que é muito utilizado em pacientes queimados para evitar e tratar infecções.…”