Passage
The β-lactam scaffold is an important feature in a class of broad-spectrum antibiotics that includes the penicillins, cephalosporins, and monobactams. These antibiotics are used to treat a variety of diseases caused by bacteria. The penicillins work by inhibiting a step in the synthesis of peptidoglycan. However, the development of antibiotic resistance in the form of enzymes such as β-lactamase is an ongoing problem.An aromatic ring linked to the β-lactam ring has been reported to participate in hydrophobic interactions with β-lactamase active sites, and an aromatic ring bonded to the nitrogen of the β-lactam has shown to be beneficial to biological activity. With this in mind, researchers synthesized a group of penicillanic acid analogues with substituted aromatic rings bonded to the β-lactam ring in an effort to overcome the challenge of antibiotic resistance. The substituents on the aromatic rings were varied, including -OCH₃ and -NO₂, to make several analogues. A key step in the synthesis of these analogues was the coupling of Compounds 1 and 2 to form a compound with two β-lactam rings (Reaction 1) .
Reaction 1The researchers studied the analogues' structure-activity relationship and antimicrobial activity against the gram-negative bacteria Escherichia coli and the gram-positive bacteria Staphylococcus aureus. Ampicillin, a penicillin derivative used to treat illnesses brought about by gram-positive and gram-negative bacteria, was used as a control. The minimal inhibitory concentrations are shown in Table 1.Table 1 Minimal Inhibitory Concentration (MIC)
The penicillanic acid analogues were tested for their effect on mammalian cell viability because toxicity to cells is also an important factor to consider for potential drug candidates. The general acceptable level of cell viability for a drug candidate is 70%. These results are shown in Figure 1.
Figure 1 Cell viability assay results
Adapted from De rosa M, Vigliotta G, Palma G, Saturnino C, Soriente A. Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation. Molecules. 2015.
-Which conclusion about the bioactivity of Compounds 3-6 is best supported by the data in Table 1 and Figure 1?

Question

Passage
The β-lactam scaffold is an important feature in a class of broad-spectrum antibiotics that includes the penicillins, cephalosporins, and monobactams. These antibiotics are used to treat a variety of diseases caused by bacteria. The penicillins work by inhibiting a step in the synthesis of peptidoglycan. However, the development of antibiotic resistance in the form of enzymes such as β-lactamase is an ongoing problem.An aromatic ring linked to the β-lactam ring has been reported to participate in hydrophobic interactions with β-lactamase active sites, and an aromatic ring bonded to the nitrogen of the β-lactam has shown to be beneficial to biological activity. With this in mind, researchers synthesized a group of penicillanic acid analogues with substituted aromatic rings bonded to the β-lactam ring in an effort to overcome the challenge of antibiotic resistance. The substituents on the aromatic rings were varied, including -OCH₃ and -NO₂, to make several analogues. A key step in the synthesis of these analogues was the coupling of Compounds 1 and 2 to form a compound with two β-lactam rings (Reaction 1) .

Reaction 1The researchers studied the analogues' structure-activity relationship and antimicrobial activity against the gram-negative bacteria Escherichia coli and the gram-positive bacteria Staphylococcus aureus. Ampicillin, a penicillin derivative used to treat illnesses brought about by gram-positive and gram-negative bacteria, was used as a control. The minimal inhibitory concentrations are shown in Table 1.Table 1 Minimal Inhibitory Concentration (MIC)

The penicillanic acid analogues were tested for their effect on mammalian cell viability because toxicity to cells is also an important factor to consider for potential drug candidates. The general acceptable level of cell viability for a drug candidate is 70%. These results are shown in Figure 1.

Figure 1 Cell viability assay results
Adapted from De rosa M, Vigliotta G, Palma G, Saturnino C, Soriente A. Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation. Molecules. 2015.
-Which conclusion about the bioactivity of Compounds 3-6 is best supported by the data in Table 1 and Figure 1?

Quizplus · Accepted Answer

11ecba2d_1273_3f7b_a3bf_dde84cb60bb5_MD0008_00 Table 1 shows minimal inhibitory concentration (MIC) values for compounds 3-6 and the control ampicillin against E. coli and S. aureus. The MIC gives the lowest concentration necessary for a compound to inhibit the growth of a bacterium. The subscript 100 indicates that 100% of the bacteria are killed at the particular concentration. All of the penicillanic acid analogues (compounds 3-6) are more active than ampicillin against S. aureus because a lower concentration of each is needed to inhibit the growth of S. aureus bacteria. Of the four penicillanic acid analogues, compound 3 has the lowest MIC₁₀₀ value of 1.1 µM, demonstrating the greatest antimicrobial activity of the tested compounds against S. aureus. (Choice A) Figure 1 shows that compounds 3-6 had varying effects on cell viabilities, ranging from 45%-95%. The passage states that 70% cell viability is generally acceptable for drug candidates. Because cell viability was above 70% for some of the compounds at the tested concentrations, it can be concluded that the addition of the substituted aromatic rings on compounds 3-6 is not always detrimental to cell viability. (Choice B) Compound 5 has the smallest effect on cell viability because, according to Figure 1, the highest percentage of cells remained alive at the three tested concentrations of Compound 5. (Choice D) Compared to ampicillin, compounds 3-6 display decreased antimicrobial activity against gram-negative bacteria. Educational objective: The minimal inhibitory concentration (MIC) gives the lowest concentration necessary to inhibit the growth of a bacterium. A compound with the lowest MIC value in a set of tested compounds indicates that the compound has the greatest antimicrobial activity of the set.

Passage The β-Lactam Scaffold Is an Important Feature in a Class