Antimicrobial screening
The primary screening against 5 key ESKAPE pathogens and 2 fungi were performed by the Community for the Antimicrobial Drug Discovery (CO-ADD), funded by the Wellcome Trust (UK) and The University of Queensland Australia.[55, 56] All synthesized compounds were evaluated at 32 µg/mL dose (approx. 100 µM) for 1) antimicrobial activity toward five pathogenic bacteria, methicillin‐resistant Staphylococcus aureus (ATCC 43300) as Gram‐positive bacteria and Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), and Pseudomonas aeruginosa (ATCC 27853) as Gram‐negative bacteria, and 2) antifungal activity towards two pathogenic fungal strains Candida albicans (ATCC 90028) and Cryptococcus neoformans var. Grubii (H99; ATCC 208821). The results of two parallel trials are presented (Table 1).
Table 1
Preliminary screening of arylsulfonamides bearing (aza)norbornane and related motifs
Compound
|
S. aureus
|
E. coli
|
K. pneumoniae
|
P. aeruginosa
|
A. baumannii
|
C. albicans
|
C. neoformans
|
VP-4556
|
105.9; 99.8[a]
|
-1.0; 3.3
|
-0.3; 5.0
|
-1.1; 1.2
|
11.9; 2.2
|
3.1; 4.6
|
-16.9; -7.0
|
VP-4580
|
20.6; 8.4
|
1.2; 5.6
|
17.3; 4.4
|
2.5; 4.8
|
10.7; 11.0
|
23.0; 32.1
|
-10.1; -13.5
|
VP-4583
|
13.2; 36.8
|
5.1; 7.0
|
13.7; 6.8
|
18.2; 9.0
|
21.9; 37.8
|
17.3; 21.8
|
-21.9; -30.5
|
VP-4584
|
16.7; 45.1
|
-5.8; -6.8
|
0.5; 1.6
|
-1.0; 6.9
|
-6.7; 6.3
|
16.6; 28.4
|
-19.2; -26.5
|
VP-4585
|
21.4; 5.4
|
-5.9; -6.2
|
-2.4; 3.0
|
1.4; 5.2
|
-15.9; -6.2
|
2.2; 4.3
|
-13.0; -28.1
|
VP-4589
|
1.1; 7.6
|
1.4; 2.2
|
0.8; 2.4
|
-1.2; -2.9
|
1.2; 7.5
|
16.3; 6.7
|
-14.4; -7.9
|
VP-4604
|
-1.8; 107.5
|
-0.9; 5.5
|
-2.7; -6.9
|
4.5; 7.2
|
-7.5; 9.7
|
12.6; 9.5
|
-2.1; 0.0
|
VP-4605
|
103.0; 99.9
|
-0.8; 0.2
|
6.0; 8.9
|
-1.9; -3.3
|
16.0; 16.2
|
12.9; 97.7
|
-49.0; 8.0
|
VP-4563
|
10.7; 16.5
|
-0.9; 5.1
|
2.2; 3.9
|
4.2; 6.7
|
18.6; 23.9
|
2.7; 5.6
|
-10.5; -2.1
|
VP-4509
|
102.1; 103.5
|
-0.0; 2.4
|
4.5; 5.7
|
-0.2; -5.4
|
16.2; 9.5
|
3.0; 4.6
|
-3.8; -6.7
|
[a] Results of two independent trials in percent of growth inhibition |
It is important to underline the relationships between the structure and activity of the tested compounds. In all cases, the compounds with the 4-methyl/bromo-benzenesulfonamide moiety showed low activity. However, several compounds maintenance and electron acceptor nitro group showed excellent activity towards the bacterium Staphylococcus aureus (ATCC 43300). Noteworthy, only nitro derivatives with a para-position of the nitro group possessed high activity.
Bacterial pathogens have rapidly developed resistance to antimicrobial agents. The antimicrobial resistance systems involve the involvement of bacterial molecular and cellular-based machinery.[57-60] These resulted in an urgent need to develop novel effective antibiotics. To confirm the antibacterial potential, we have examined the toxicity of these drugs towards methicillin‐resistant Staphylococcus aureus. Thus, a number of compounds (VP-4556, VP-4604, VP-4605, and VP-4509) were discovered that totally inhibited the growth of methicillin‐resistant Staphylococcus aureus with growth inhibition GI >95%. All five highly active compounds contained a 4-nitrobenzenesulfonamide motif, indicating its beneficial role for inducing antimicrobial effect. Among them, there are two cage compounds VP-4556 and VP-4509 and two containing morpholine VP-4604 and piperidine VP-4604 substituents, respectively. This strain of bacteria spread mostly in hospitals and has resistance to multiple antibiotics. Therefore, obtaining substances with antibacterial activity to this strain will reduce the number of nosocomial infections, which provides a lot of death and side effects.[61] Thus, compounds with 4-nitrobenzenesulfonamide motif possessed high growth inhibition activity towards drug-resistant S. aureus and could be promising antimicrobial agents.
The minimal inhibitory concentration (MIC; µg/mL) measurements were performed for compounds with significant microbial growth inhibition (VP-4556, VP-4604, VP-4605 and VP-4509) toward Staphylococcus aureus (ATCC 43300), using ceftriaxone, as a reference drug. At the same time, for the active compounds, primary cytotoxicity toward human embryonic kidney cell line and hemolysis of human red blood cells human cells was determined. Haemolysis assay is the most commonly used for initial toxicity investigation of different agents. Human erythrocytes are the most frequently used for the preliminary in vitro study of the haemolytic activity of antimicrobial and other drugs.[62] Compounds VP-4556, VP-4604, VP-4605, and VP-4509 have the best antibacterial activity, comparable to ceftriaxone. Cytotoxic concentration (CC50) of the compound VP-4605 is approximately 5 times higher (18.6 and 20.3 µg/mL) than that of MIC (4 µg/mL). Another tested compounds VP-4556, VP-4604, and VP-4509 were tolerated and non-toxic for human cells, as the cytotoxic and hemolytic dose was higher than the therapeutic dose (Table 2).
Taking into account the primary screening results, we checked the antibacterial effect of most active compounds using the MTT assay. This method is based on the changes of a colour reaction due to the metabolism of the MTT reagent in bacteria. The substances under study were solved in DMSO, thus, we used DMSO as a substance for comparison in equal doses like the doses of the studied compound.
Table 2. The minimal inhibitory concentration (MIC; µg/mL) for compounds with significant microbial growth inhibition (VP-4556, VP-4604, VP-4605, and VP-4509) toward Staphylococcus aureus (ATCC 43300) and primary cytotoxicity toward human embryonic kidney cell line and hemolysis of human red blood cells (RBC)
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)
[a] Results of two independent trials.
The most active compounds were tested toward Staphylococcus aureus ATCC25923. Figure 1. presents the effect of compounds VP-4556, VP-4604, VP-4605, and VP-4509 towards S. aureus. Compound VP-4556 was most active towards S. aureus (Fig. 2) in a low concentration.
Primary screening data showed low activity of the compounds toward Gram-negative bacteria Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), and Pseudomonas aeruginosa (ATCC 27853). In addition, we tested the most active compounds towards another strain of the Gram-negative bacteria Pseudomonas aeruginosa (ATCC9027) (Fig. 3). It was found, that compounds VP-4556, VP-4604, VP-4605, and VP-4509 possessed high antibacterial activity toward gram-negative bacteria P. aeruginosa (ATCC9027).
In conclusion, the results obtained by screening methicillin-resistant Staphylococcus aureus (MRSA) strain and other microorganisms differ from the results obtained at using the MTT method. These results allow us to argue that 4-nitrobenzenesulfonamide derivatives have a specific effect on bacteria, rather than a general toxic effect. We can suggest that the synthesized 4-nitrobenzenesulfonamides cause the destruction of bacterial walls by interacting with structural elements of the bacterial wall, as well as specifically affect them or some internal mechanisms of bacteria functioning. In future, we are going to identify which of the biomolecules could interact with the studied 4-nitrobenzenesulfonamide.
Cytotoxicity
The antimicrobial agents needs to demonstrate low or no toxicity towards mammalian cells.[63, 64] Cytotoxicity of the five most active compounds (VP-4509, VP-4556, VP-4604, VP-4605) was father evaluated towards human keratinocytes of HaCaT cell line, Balb/c 3T3 line (murine fibroblasts) and lymphocytes of healthy human donor. Studied compounds had low cytotoxic action towards non-tumor cells of HaCaT line (human keratinocytes) and Balb/c 3T3 line (murine fibroblasts) (Fig. 4). Compounds did not reached the CC50 value for Balb/c 3T3 cells up to 2,500 µM. The inhibition of growth of Balb/c 3T3 cells equaled in the range of 11.1‒45.6% at the action of studied derivatives at this dose. CC50 value of compound VP-4556 for HaCaT cells reached the 1792 µM. The CC50 value of compounds VP-4509 and VP-4605 for HaCaT cells was approximately 2500 µM. Compound VP-4604 inhibited the growth of HaCaT cells by 44.1% at 2,500 µM. DMSO demonstrated low toxicity for HaCaT and Balb/c 3T3 cells. It inhibited the growth of HaCaT cells by 41.9% at 2500 µM.
Doxorubicin was used as a standard positive control drug, and it demonstrated high cytotoxicity toward HaCaT and Balb/c 3T3 cells. Doxorubicin showed higher cytotoxic effect than studied compounds toward HaCaT and Balb/c 3T3 cells with the CC50 value of 0.8 µM and 0.9 µM, respectively.
Studied derivatives demonstrated low toxicity toward mitogen-activated lymphocytes isolated from healthy adult human peripheral blood. The CC50 value of studied compounds VP-4509, VP-4556, VP-4604, and VP-4605 was approximately 2,500 µM for mitogen-activated human blood lymphocytes (Fig. 5).
Thus, studied compounds had low toxicity toward non-tumor cells of HaCaT line (human keratinocytes) and Balb/c 3T3 line (murine fibroblasts), and mitogen-activated lymphocytes isolated from healthy adult human peripheral blood.