Synthesis, antineoplastic and cytotoxic activities of some mononuclear Ru(II) complexes

Figures & data

Scheme 1.  Preparation of ligands (r-btsz and r-binh).

Scheme 2.  Preparation of cis-[Ru(S)₂Cl₂].

Scheme 3.  Preparation of tris chelates from cis-[Ru(S)₂Cl₂].

Figure 1.  Structures of the ruthenium(II) complexes, where N = 1,10-phenanthroline/2,2′-bipyridine, R= 4-OH, 4-CH₃, 3,4-di-OCH₃.

Table 1.  Antineoplastic activity of ruthenium complexes against EAC bearing mice.

Parameter	Total body weight (g)	Mean survival time (days)	ILS%	Tumor volume (mL)	Viable cells in ascitic fluid (%)
Group I	24.2 ± 0.5	—	—	—	—
Group II	27.8 ± 0.6	21	—	3.4 ± 0.3	94.8 ± 3.8
Group III	19.6 ± 0.5	22	5	—	—
Group IV	22.4 ± 0.4	29	38	0.9 ± 0.07	36.2 ± 1.1
Group V	23.2 ± 0.7	26	24	1.1 ± 0.03	43.5 ± 1.4
Group VI	23.7 ± 0.8	25	19	1.4 ± 0.04	45.6 ± 1.2
Group VII	28.4 ± 0.6	28	33	1.0 ± 0.04	38.8 ± 1.7
Group VIII	25.3 ± 0.3	24	14	1.2 ± 0.03	46.9 ± 1.4
Group IX	26.8 ± 0.2	32	52	0.7 ± 0.03	28.4 ± 1.6
Group X	26.4 ± 0.5	26	24	1.1 ± 0.02	43.4 ± 1.3
Group XI	24.2 ± 0.5	25	19	1.4 ± 0.06	45.2 ± 1.4
Group XII	22.9 ± 0.4	28	33	1.0 ± 0.02	38.6 ± 1.8
Group XIII	24.8 ± 0.6	26	24	1.1 ± 0.04	43.8 ± 1.2
Group XIV	22.6 ± 0.8	23	10	1.3 ± 0.06	47.9 ± 1.5
GroupXV	23.8 ± 0.2	25	19	1.9 ± 0.04	45.1 ± 1.3

Note. Values are mean ± SEM. ILS% = [(mean survival of treated group)/(mean survival of control group) – 1] × 100. Group I, vehicle (5 mL/kg); Group II, EAC (2 × 10⁶ cells/mouse); Group III, cisplatin (2 mg/kg) + EAC; Group IV, Ru 1; Group IV–Group XV, ruthenium complexes (2 mg/kg) + EAC.

Table 2.  Cytotoxic studies of ligands and ruthenium compounds.

Compound	IC50^a (μM)
	L1210	Molt 4/C8	CEM
4-OH-btsz	244 ± 8	328 ± 12	223 ± 4
4-CH3-btsz	186 ± 21	126 ± 34	136 ± 22
3,4-di-OCH3-btsz	72 ± 4	88 ± 12	84 ± 33
4-OH-binh	232 ± 12	180 ± 24	163 ± 26
4-CH3-binh	94 ± 22	227 ± 13	128 ± 42
3,4-di-OCH3-binh	64 ± 32	96 ± 28	202 ± 64
Ru 1	18 ± 4	3.1 ± 1.8	2.9 ± 0.8
Ru 2	32 ± 12	24 ± 0.6	19 ± 5
Ru 3	0.78 ± 0.6	0.21 ± 0.02	0.24 ± 0.21
Ru 4	8.7 ± 0.3	0.65 ± 0.11	0.96 ± 0.53
Ru 5	0.82 ± 0.04	0.39 ± 0.03	0.48 ± 0.16
Ru 6	1.8 ± 0.2	1.2 ± 0.4	0.19 ± 0.14
Ru 7	0.75 ± 0.06	0.29 ± 0.07	0.16 ± 0.09
Ru 8	5.9 ± 1.3	1.4 ± 0.1	2.1 ± 0.2
Ru 9	0.91 ± 0.08	0.26 ± 0.03	0.22 ± 0.02
Ru 10	3.9 ± 1.5	0.92 ± 0.24	2.3 ± 0.5
Ru 11	1.5 ± 0.3	0.36 ± 0.04	1.6 ± 0.4
Ru 12	12 ± 1.4	18 ± 12	10 ± 06

^a50% inhibitory concentration, required to inhibit tumor cell proliferation by 50%.