Novel tetrahydronaphthalen-1-yl-phenethyl ureas: synthesis and dual antibacterial-anticancer activities

Figures & data

Figure 1. Examples of commercially available urea drugs 1–5.

Figure 2. Phenethylamine 6, tyramine 7, dopamine 8, tametraline 9, and 1-aminotetralin derivative 10.

Scheme 1. Synthesis of substituted tetrahydronaphthalen-1-yl-phenethyl ureas 14–18.

Table 1. Antibacterial activity of the synthesised ureas 14–18.

Bacteria	Number of ureas	Disc diffusion test^a Concentrations (µM)			MIC^b (µM)	Negative control	Standard antibiotic discs^c
		1000	500	250		DMSO	OFX	NET30
Acinetobacter baumannii	14	–	–	–	–	–	16 MIC: 0.5 µg/ml	13 MIC: 4 µg/ml
	15	–	–	–	–
	16	13	10	5	7.8125
	17	15	8	6	7.8125
	18	16	10	6	7.8125
Enterococcus faecalis	14	–	–	–	–	–	11 MIC: 2.5 µg/ml	9 MIC: 32 µg/ml
	15	–	–	–	–
	16	7	6	–	3.90
	17	10	7	–	0.97
	18	13	7	5	0.97
Pseudomonas aeruginosa	14	–	–	–	–	–	23 MIC: 11.4 µg/ml	16 MIC: 4 µg/ml
	15	5	5	5	15.625
	16	10	8	7	7.8125
	17	10	10	7	7.8125
	18	15	10	9	3.90
Staphylococcus aureus MRSA	14	–	–	–	–	–	24 MIC: 1.2 µg/ml	21 MIC: 0.8 µg/ml
	15	6	5	–	15.625
	16	13	6	5	7.8125
	17	14	13	8	7.8125
	18	15	12	5	3.90

^aInhibitory zone diameter (mm) varies based on different concentrations.

^bMIC: minimum inhibitory concentrations.

^cOFX refers to ofloxacin at a concentration of 10 μg/disc, while NET-30 indicates netilmycin at 30 μg/disc. Both were utilised as benchmark antibiotic discs from Oxoid.

Table 2. Cytotoxic activity (IC₅₀, μM) of the synthesised ureas (n = 4).

Test molecules	SH-SY5Y	HeLa cells	PCS-201-012 cells
14	9.7	2.6	7.9
15	8.9	142	225.7
16	19.1	32.4	>500
17	9.7	251	379.8
18	10.2	364.4	373.5
Cisplatin	10	75 > IC50 > 50	>100
Melphalan	2.2	61	–

Figure 3. SH-SY5Y cells were exposed to produced ureas (12.5–500 M) for 48 h, and cytotoxicity was assessed using the WST-8 assay. GraphPad Prism 7.00 (GraphPad Software, La Jolla, CA) was used for statistical analysis, and ANOVA: Dunnett’s multiple comparison test calculated the results. *p < 0.01 when compared to the control group.

Figure 4. HeLa cells were exposed to produced ureas (12.5–500 M) for 48 h, and cytotoxicity was assessed using the WST-8 assay. GraphPad Prism 7.00 (GraphPad Software, La Jolla, CA) was used for statistical analysis, and ANOVA: Dunnett’s multiple comparison test calculated the results. *p < 0.01 when compared to the control group.

Figure 5. Percentage of cytotoxicity evaluated using the WST-8 test on PCS-201-012 cells after 48 h of exposure to produced ureas 14–18 (12.5–500 M). GraphPad Prism 7.00 (GraphPad Software, La Jolla, CA) was used for statistical analysis, and ANOVA: Dunnett’s multiple comparison test calculated the results. *p < 0.01 when compared to the control group.

Table 3. SI values of the synthesised molecules (n = 4).

Test molecules	SI value (SH-SY5Y cells)	SI value (HeLa cells)
14	0.81	3.04
15	25.26	1.58
16	26.10	15.4
17	39.08	1.51
18	36.72	1.02

Data availability statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy.