Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine − synthesis, cytostatic, antiviral and antioxidative studies

Figures & data

Table 1.  Interaction with DPPH, in vitro inhibition of LP, soybean LOX and theoretically calculated Clog p values.

Compd.	DPPH^a (%)		LP^a (%)	LOX inhibition^a (%)	Clog p ^b
	20 min	60 min
4b	61.2	69.2	na	na	1.92
4c	66.6	77.4	na	na	2.25
5a	3.7	3.5	1.0	na	3.45
5b	12.0	15.7	2.4	29.4	4.01
5c	12.6	16.7	2.0	35.4	3.71
5d	2.4	1.3	2.0	45.2	4.08
5e	10.0	13.2	3.0	51.0	5.05
5f	8.0	15.0	1.2	9.6	3.51
5g	68.5	72.0	2.0	14.1	1.03
NDGA	84	91	−	81	−
Trolox	−	−	67	−	−

^a Concentration of the tested compound: 100 μM;

^b Clog p values were calculated by the ClogP programme of Biobyte Corp³⁵;

na− no activity.

Figure 1.  Synthesis of PQ semicarbazide derivatives 5a–g.

Figure 2.  Atom enumeration of compounds 4 and 5.

Table 2.  Inhibitory effects of PQ semicarbazide derivatives 5a-g and their synthetic precursors 4 on the proliferation of malignant tumour cell lines.

Compd.	Structural formula	IC50^a (µM)
		HCT 116	MCF-7	H 460	L1210	CEM	HeLa
4b		> 100	> 100	> 100	> 250	> 250	> 250
4c		> 100	> 100	> 100	≥ 250	> 250	> 250
4d		> 100	79 ± 16	> 100	−	−	−
5a		> 100	11 ± 8	> 100	> 250	> 250	> 250
5b		> 100	16 ± 12	> 100	144 ± 86	≥ 250	150 ± 74
5c		> 100	1 ± 0.2	> 100	> 250	> 250	> 250
5d		> 100	4 ± 0.3	> 100	> 250	> 250	> 250
5e		17 ± 1	4 ± 0.6	17 ± 0.9	18 ± 2	11 ± 1	16 ± 1
5f		16 ± 2	1.5 ± 1.3	32 ± 4	21 ± 1	21 ± 5	12 ± 11
5g		≥ 100	3 ± 0.2	> 100	173 ± 45	179 ± 34	202 ± 67
PQ20		20 ± 6	28 ± 10	30 ± 7	nt	nt	nt

^a IC₅₀; the concentration that causes 50% growth inhibition.

^b nt; not tested.

C-QSAR Database: Biobyte Corp., 201 West 4th Street, Suite 204, Claremont, CA 91711.

 Google Scholar