A detailed in vitro study of naproxen metal complexes in quest of new therapeutic possibilities

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 1 July 2016

Figures & data

Table 1 Results of in vitro anti-inflammatory activity of Naproxen metal complexes.

Group	Concentration	Absorbance (560 nm)	% protection of HRBC membrane
Control	–	0.112 ± 0.001	–
Standard (Naproxen)	100 μg/ml	0.093 ± 0.001^a	68.75
	1000 μg/ml	0.092 ± 0.0003^a	69.64
	2000 μg/ml	0.088 ± 0.001^a	73.21
Copper-Naproxen complex	100 μg/ml	0.165 ± 0.002^a	4.46
	1000 μg/ml	0.178 ± 0.001^a	−7.14
	2000 μg/ml	0.216 ± 0.001^a	−41.07
Cobalt-Naproxen complex	100 μg/ml	0.090 ± 0.001^a	71.43
	1000 μg/ml	0.078 ± 0.001^a	82.14
	2000 μg/ml	0.074 ± 0.0008^a	85.71
Iron-Naproxen complex	100 μg/ml	0.082 ± 0.001^a	78.57
	1000 μg/ml	0.080 ± 0.0008^a	80.36
	2000 μg/ml	0.075 ± 0.0003^a	84.82
Silver-Naproxen complex	100 μg/ml	0.109 ± 0.001	54.46
	1000 μg/ml	0.114 ± 0.0006	50.00
	2000 μg/ml	0.139 ± 0.001^a	27.68
Zinc-Naproxen complex	100 μg/ml	0.091 ± 0.0005^a	70.54
	1000 μg/ml	0.086 ± 0.0008^a	75.00
	2000 μg/ml	0.084 ± 0.001^a	76.79

Results were expressed as mean ± SEM for n = 3 observations.

a P < 0.001 was considered significant compared with control.

Table 2 Antimicrobial activity of Naproxen and metal complexes.

Test microorganisms	Zone of inhibition (in mm by transparent scale)
	Ciprofloxacin	Naproxen	N-Cu	N-Co	N-Fe	N-Ag	N-Zn
Gram positive bacteria
Bacillus cereus	32	–	14	13	5	18	21
Bacillus megaterium	31	–	12	15	3	16	18
Bacillus subtilis	30	–	17	15	7	21	17
Staphylococcus aureus	28	–	6	10	8	19	12
Sarcina lutea	31	–	–	–	9	17	15
Fungi (Miconazole as standard)
Candida albicans	28	–	10	9	–	15	13
Aspergillus niger	24	–	7	–	–	13	16
Aspergillus flavus	25	–	9	–	8	16	18
Saccharomyces cerevisiae	22	–	12	7	6	19	10
Gram negative bacteria
Escherichia coli	37	–	11	17	24	20	8
Pseudomonas aeruginosa	33	–	9	14	13	17	7
Salmonella paratyphi	28	–	–	15	16	14	10
Salmonella typhi	26	–	–	–	12	9	4
Shigella boydii	29	–	13	–	–	11	6
Shigella dysenteriae	27	–	14	–	–	13	9
Vibrio mimicus	30	–	3	5	6	7	3

Table 3 Percent of mortality of the nauplii of Naproxen metal complexes.

Sl. no.	Concentration (C) (μg/ml)	Mortality (%)
		Naproxen	N-Cu	N-Co	N-Fe	N-Ag	N-Zn
1	400	100	20	20	100	20	20
2	200	100	10	20	100	10	10
3	100	100	10	10	100	10	10
4	50	100	0	0	100	10	0
5	25	100	0	0	100	0	0
6	12.5	60	0	0	100	0	0
7	6.25	50	0	0	100	0	0
8	3.125	20	0	0	70	0	0
9	1.5625	0	0	0	50	0	0
10	0.78125	0	0	0	50	0	0

Table 4 LC₅₀ values of the test samples of Naproxen metal chelates.

Test sample	Regression line	R^2	LC50 (μg/ml)
VS	y = 33.22x + 58.78	0.958	0.544
Naproxen	y = 44.091x + 7.9996	0.864	8.96
N-Cu	y = 46.399x − 3.5343	0.619	14.25
N-Co	y = 47.449x − 4.2923	0.638	13.94
N-Fe	y = 19.126x + 63.141	0.649	0.205
N-Ag	y = 46.643x − 3.2877	0.733	13.88
N-Zn	y = 46.039x − 3.5343	0.619	14.55

Figure 1 DPPH scavenging activity of Naproxen metal and its complex. N-Co: Naproxen Cobalt complex, N-Fe: Naproxen Iron complex, N-Zn: Naproxen Zinc complex, N-Ag: Naproxen Silver complex, N-Cu: Naproxen Copper complex.

Figure 2 ABTS scavenging activity of Naproxen metal and its complex.

Figure 3 Reducing potential of Naproxen metal and its complex.

Figure 4 Superoxide potential of Naproxen metal and its complex.

Table 5 Total antioxidant capacity of Naproxen metal and its derived complexes.

Name of sample	Absorbance for 500 ppm at 695 nm	Total antioxidant capacity (AAE/g)
Naproxen	0.554 ± 0.001	0.81 ± 0.01
N-Cu	0.0823 ± 0.004	1.37 ± 0.03
N-Co	0.0846 ± 0.005	1.38 ± 0.02
N-Fe	0.0921 ± 0.018	1.54 ± 0.04
N-Zn	0.0774 ± 0.032	1.29 ± 0.01
N-Ag	0.0667 ± 0.017	1.19 ± 0.05

Values are expressed as mean ± SD (n = 3).