Drugs That Changed Society: History and Current Status of the Early Antibiotics: Salvarsan, Sulfonamides, and β-Lactams

Abstract

The appearance of antibiotic drugs revolutionized the possibilities for treatment of diseases with high mortality such as pneumonia, sepsis, plaque, diphtheria, tetanus, typhoid fever, and tuberculosis. Today fewer than 1% of mortalities in high income countries are caused by diseases caused by bacteria. However, it should be recalled that the antibiotics were introduced in parallel with sanitation including sewerage, piped drinking water, high standard of living and improved understanding of the connection between food and health. Development of salvarsan, sulfonamides, and β-lactams into efficient drugs is described. The effects on life expectancy and life quality of these new drugs are indicated.

The Ascension of Targeted Covalent Inhibitors

“…This reflects that historically most drug discovery programs avoided covalent drugs due to the belief that reversible drugs can achieve the desired target product profiles and avoid potential toxicity risks. Until the 1980s, many of the approved covalent drugs were antibiotics (47%), which reflects their immense impact on human health through revolutionizing the treatment of infectious diseases . The following decade (1990s) saw the approval of a broader range of covalent drugs with the advent of proton-pump and anti-platelet inhibitors, which both became blockbuster drug classes.…”

“…Until the 1980s, many of the approved covalent drugs were antibiotics (47%), which reflects their immense impact on human health through revolutionizing the treatment of infectious diseases. 12 The following decade (1990s) saw the approval of a broader range of covalent drugs with the advent of proton-pump and anti-platelet inhibitors, which both became blockbuster drug classes. Up until this point, these drugs were either discovered through protease inhibitors, the first class of direct anti-viral drugs for the treatment of hepatitis C. 13 In addition, this period saw approval of proteosome inhibitors which positively impacted hematological cancer therapy.…”

Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides

“…Most likely the increased death rate for cancer is caused by an increase in life expectancy since cancer is a disease most frequently appearing in populations of elderly persons. Recent statistics confirm that cancer is the main reason for death among older people in countries with a high human development index [ 1 ], where death rates of communicative diseases are almost negligible [ 2 , 3 ]. Among men, lung cancer, colorectum cancer and liver cancer are the main cause of death [ 2 ].…”

Ligation Motifs in Zinc-Bound Sulfonamide Drugs Assayed by IR Ion Spectroscopy

“…Since their discovery in 1935, sulfonamide drugs, derivatives of 4-aminobenzenesulfonamide (H 2 N-C 6 H 4 -SO 2 NH 2 ), have been used extensively as wide-spectrum antibiotics for the treatment of human and animal bacterial infections [ 1 , 2 , 3 , 4 ]. Their bacteriostatic action is exerted by inhibiting the use of 4-aminobenzoic acid, which is essential for the synthesis of folic acid, a fundamental developmental factor in the metabolism of microbes.…”

“…Sulfathiazole (STZ) and sulfadiazine (SDZ), the sulfa drugs that are specifically addressed in this contribution, belong to the family of clinically used sulfonamides for the treatment of infectious diseases [ 1 ]. Their structure, comprising two tautomeric (amido and imido) forms [ 16 ], is depicted in Scheme 1 .…”