Synthesis and preliminary evaluation in vitro of novel naproxen-dendritic peptide conjugates

Figures & data

Figure 1.  The structure of the target molecules.

Table 1.  Water-solubility of these conjugates.

Compound	Mw	Numbers of -COOH	Water solubility (mg/ml)
			pH 3	pH 5	pH 7
NAP-G1-Asp	575.52	4	2.55	4.09	6.12
NAP-G1-Glu	617.60	4	2.06	3.83	5.23
NAP-G2-Asp	1035.87	8	11.35	15.25	17.22
NAP-G2-Glu	1134.06	8	9.10	13.88	16.46
NAP	230.26	1	0.02	0.18	0.19

Figure 2.  Percentage of conjugates bound to HAP at 1 h or over 24 h.

Figure 3.  Effect of HAP concentration on the degree of HAP binding (NAP-G₂-Asp 500 μg/ml).

Figure 4.  Effect of NAP-G₂-Asp concentration on the degree of HAP binding (HAP  25 mg/ml).

Scheme 1.  (a) DCC, HOSu, NMM, 3a, 67%, 3b, 55%; (b) TFA, CH₂Cl₂, 99%; (c) Naproxen, DCC, DMAP, 5a, 74%, 5b, 78%; (d) H₂, Pd/C, 90%.

Scheme 2.  (a) HBTU/Hobt, DIPEA, 6a, 57%, 6b, 49%; (b) TFA, CH₂Cl₂, 99% (c) Naproxen, DCC, DMAP, 8a, 62%, 8b, 69%; (d) H₂, Pd/C, 89%.

Figure 5.  Release of naproxen from HAP bound NAP-G₂-Asp under physiological conditions.