**3. Classification**

antibacterials in ancient populations. It was found than the bone sample from Sudanese Nu‐ bian (A.D. 350 to 550) was labeled by the antibiotic tetracycline and their dietary regime con‐ tained tetracycline-containing materials by X-group cemetery and other advanced technologies [4; 5]. Moreover, another study showed that, bones from the Dakhleh Oasis, Egypt, in a late Roman period, exhibit discrete fluorochromelabelling, exactly like the teeth from patients treated with tetracycline [6]. A large number of customs and anecdotes can al‐ so reveal the occurrences of other antibacterials. One popular anecdote is about the antibiot‐ ic-like properties of red soil from the Hashemite Kingdom of Jordan. Interestingly, red soil was used for treating skin infections and diaper rash in the past and is still used in some communities today as an inexpensive alternative to antibiotics [7]. In fact, recently, many pharmaceutical antibiotics, such as streptomycin, actinomycin, erythromycin, vancomycin,

The traditional Chinese medicine is the summary of experience about Chinese medical treat‐ ment over millennia and may contain a lot of unknown antibiotics [9]. Many traditional Chi‐ nese medicines were tested and found effective against four common oral bacteria [10]. Discovery of active components in the ancient herbs could enrich the arsenal of antimicrobi‐

Bacteria were first identified in the 1670s by van Leeuwenhoek, following his invention of the microscope. The relationship between bacteria and diseases gradually set up in the nine‐ teenth century. Since then, researchers started to try and find effective antibacterial agents.

Paul Ehrlich is the father of chemotherapy and was honored with the Nobel prize due to the molecular side-chain theory of immunity. His concept of "magic bullet" is that the chemicals selectively target only disease-causing microbes but not the host cells. In 1906, Ehrlich, together with Bertheim, developed hundreds of derivatives of Atoxyl, and final‐ ly discovered compound 606, a gold powder [9; 11]. In 1909, he found that Compound 606 could cure syphilis-infected rabbits in experiments; it could also improve terminal patients with dementia and cured early stage patients with infected sores [11]. It was publicly released as salvarsan in 1910. Despite the adverse side effects, salvarsan and it's derivative neosalvarsan kept the status of the most frequently prescribed drug until the introduction of penicillin in the 1940s [12]. Amazingly, the chemical structure of salvar‐

The systematic screening approach introduced by Paul Ehrlich became the cornerstone of drug search strategies in the pharmaceutical industry. Sulfonamidochrysoidine (also named prontosil), the first commercially available antibiotic, was first synthesized by Bayer chem‐ ists Josef Klarer and Fritz Mietzsch in 1930s by this approach. Then Gerhard Domagk found its effect against Streptococcus pyogenes in mice [14]. Four years later he received the Noble Prize. Eventually prontosil was recognized as a precursor for a new class of antibacterial

nystatin and amphotericin, were produced from the soil actinomycetes [8].

als used by the mainstream medicine.

290 Drug Discovery

**2.2. Foundation of the antibiotic era**

san hadn't been known until 2005 [13].

agents— sulfonamides.

Antibacterials are commonly classified based on their mechanism of action or spectrum of activity. The main classes of antibacterial drugs target only four classical bacterial functions: bacterial-cell-wall biosynthesis (e.g., penicillin and vancomycin); bacterial protein biosynthe‐ sis (e.g., aminoglycoside and macrolide); DNA and RNA replication (e.g., ciprofloxacin and rifampin); and folate coenzyme biosynthesis (e.g., sulfamethoxazole) [18]. Antibacterials that target the cell wall or cell membrane or essential bacterial enzymes are more likely to be bac‐ tericidal; but generally the bacteriostatic is the antibacterial drugs that inhibits protein syn‐ thesis [19]. Another way to distinguish the antibiotics is based on their target specificity. The broad-spectrum antibiotic affects a wide range of disease-causing bacteria, including both Gram-positive and Gram-negative bacteria, in contrast to a narrow-spectrum antibiotic, which acts against specific families of bacteria. For example, ampicillin is a widely used broad-spectrum antibiotic.
