Spectral analysis and in vitro cytotoxicity profiles of novel organotin(IV) esters of 2-maleimidopropanoic acid

Figures & data

Scheme 1 Synthesis of organotin (IV) esters.

Table I.  Physical and analytical data for complexes 1–6 and the ligand 7.

	Mol.	M.P.	Yield	Elemental analysis calculated (found)
Cpd.	formula	(°C)	(%)	%C	%H	%N	%Sn
(1)	C10H15NO4Sn	95	81	36.18(36.02)	4.55(4.32)	4.22(4.10)	35.76(35.48)
(2)	C13H21NO4Sn	82	77	41.75(41.38)	5.66(5.43)	3.76(3.65)	31.74(31.53)
(3)	C16H27NO4Sn	Gel	83	46.18(46.05)	6.54(6.31)	3.37(3.22)	28.53(28.29)
(4)	C19H33NO4Sn	133	86	49.81(49.57)	7.26(7.09)	3.06(2.95)	25.91(25.75)
(5)	C25H21NO4Sn	178	88	57.95(57.76)	4.09(4.01)	2.70(2.49)	22.91(22.85)
(6)	C28H27NO4Sn	145	88	60.03(59.87)	4.86(4.66)	2.50(2.32)	21.19(21.04)
(7)	C7H7NO4	118	84	49.71(49.67)	4.17(4.15)	8.28(8.25)	–

Table II.  FT IR data for complexes 1–6 and ligand 7 (cm⁻¹).

Comp.	ν(COO)asym	ν(COO)sym	Δν	ν(Sn–C)	ν(O–Sn)
(1)	1590	1387	203	521	461
(2)	1596	1372	224	526	414
(3)	1580	1371	209	531	445
(4)	1574	1365	209	522	437
(5)	1588	1369	219	540	432
(6)	1574	1370	204	525	426
(7)	1695	1357	338	–	–

Figure 1 (a) Polymeric geometry, (b) tetrahedral geometry, (c) trigonal bipyrmidal geometry and numbering scheme for NMR.

Table III.  ^119mSn Mössbauer spectral data for complexes 1–6 (mm s⁻¹).

Compound	QS	IS	Γ1	Γ2	ρ = QS/IS
(1)	3.57	1.31	0.91	0.89	2.72
(2)	3.56	1.29	0.82	0.80	2.69
(3)	3.52	1.41	0.84	0.78	2.50
(4)	3.60	1.36	0.97	0.92	2.64
(5)	3.67	1.29	0.99	0.73	2.84
(6)	3.04	1.48	0.96	0.87	2.05

Table IV.  ¹H NMR data of 1–7 with ²J(¹¹⁹Sn-¹H) in parenthesis.

Proton	1	2	3	4	5	6	7
2	4.85q	4.91q	4.69q	4.77q	4.75q	4.71q	4.82q
3	1.72d	1.77d	1.68d	1.63d	1.60d	1.87d	1.78d
5	6.91s	6.87s	6.61s	6.92s	6.78s	6.99s	6.97s
6	0.14s(56)	0.95q(52)	0.74t(60)	0.85t(58)	–	2.76s(33)	–
7	–	0.76t	1.321m	1.61m	7.03m	–	–
8	–	–	1.13t	1.33m	7.00m	7.13m	–
9	–	–	–	0.89t	6.93m	7.31m	–
10	–	–	–	–	–	7.40m	–

Table V.  ¹³C NMR data of 1–7 with ¹J(¹¹⁹Sn-¹³C) in parenthesis.

Carbon	1	2	3	4	5	6	7
1	179.87	171.45	175.69	180.36	165.87	171.23	170.34
2	54.21	53.69	55.02	54.33	53.44	53.67	53.55
3	17.11	18.27	18.45	17.02	16.89	17.33	17.42
4	169.88	165.22	163.34	167.41	168.47	168.24	167.31
5	135.62	138.41	137.20	139.79	136.97	137.11	137.25
6	− 2.13(393)	4.5(371)	20.43(403)	16.74(366)	140(687)	20.35(638)	–
7	–	12.34(44)	17.04(13)	27.4(18)	136(63)	139.5(16)	–
8	–	–	19.25(67)	27.95(60)	128.3(85)	123.6(28)	–
9	–	–	–	11.47	126.7(07)	131.4(40)	–
10	–	–	–	–	–	119.7	–
^119Sn	136.14	117.3	104.46	113.67	− 94.63	− 104.55

Table VI.  In vitro inhibition doses ID₅₀ (ng/mL) of compounds 1–7 against seven tumoral cell lines of human origin.

	A498	EVSAT	H226	IGROV	M19	MCF7	WiDr
1	222	147	178	255	150	24	361
2	122	145	158	29	177	255	331
3	144	122	255	89	111	158	165
4	36	66	21	112	140	21	187
5	144	20	174	15	08	23	100
6	22	71	128	36	41	28	89
7	336	214	325	258	333	273	239
Do	28	44	68	107	23	35	62
Cp	1432	658	471	478	321	214	105
5-Fu	2214	325	164	205	301	54	82
Mt	3094	210	65	25	212	100	64
Et	514	531	438	328	155	84	103

^{cell lines}: A498 (renal cancer), EVSA-T (mammary cancer), H226 (lung cancer), IGROV (ovarian cancer), M19 (melanoma), MCF-7 (mammary cancer) and WiDr (colon cancer); ^{reference drugs}: Do (doxorubicin), Cp (cisplatin), 5-Fu (5-fluorouracil), Mt (methotrexate) and Et (etopside).

Table VII.  In vitro anti-leishmanial effect of 1–7 (mM) in promastigote stage.

	Anti-leishmanial IC50/IC100
Compound	L. major	L major (Pak.)	L. tropica	L. mex mex	L. donovani
(1)	0.42/0.74	0.44/1.08	0.62/0.74	0.96/0.74	0.42/0.74
(2)	0.41/0.81	0.43/0.97	0.53/0.89	0.55/1.03	0.36/1.23
(3)	0.40/1.31	0.32/0.88	0.42/0.77	0.33/0.85	0.32/0.73
(4)	0.29/0.98	0.28/0.66	0.33/0.53	0.22/0.71	0.30/0.44
(5)	0.22/1.02	0.19/0.36	0.21/0.22	0.18/0.54	0.33/0.31
(6)	0.07/0.32	0.10/0.25	0.22/0.14	0.09/0.33	0.04/0.29
(7)	0.97/1.65	1.12/1.33	0.98/1.87	1.05/1.32	1.11/1.25

Table VIII.  In vitro anti-fungal effect of 1–7.

	% Inhibition @ 0.01, 0.02, 0.05, 0.1 mM
Fungi	(1)	(2)	(3)	(4)	(5)	(6)	(7)
A	25,28,33,41	33,31,36,40	31,44,52,51	44,22,22,45	56,64,61,72	77,85,88,89	10,23,22,31
B	33,38,39,51	41,43,56,62	35,40,52,63	37,41,33,55	57,61,70,73	65,66,70,71	12,11,22,20
C	08,11,15,22	22,21,42,55	09,18,44,53	36,20,31,39	22,44,38,54	88,90,98,100	11,36,08,01
D	10,28,39,55	22,29,41,45	36,39,66,71	30,39,59,74	23,55,63,74	24,28,29,100	22,28,31,30
E	02,09,14,22	28,29,33,32	44,45,58,88	45,63,65,71	66,68,71,74	66,68,69,73	33,32,39,44
F	33,38,39,51	41,43,56,62	35,40,52,63	37,41,33,55	57,61,70,73	65,66,70,71	12,11,22,20
G	08,11,15,22	22,21,42,55	09,18,44,53	36,20,31,39	22,44,38,54	88,90,98,100	11,36,08,01
H	10,28,39,55	22,29,41,45	36,39,66,71	30,39,59,74	23,55,63,74	24,28,29,100	22,28,31,30
I	02,09,14,22	28,29,33,32	44,45,58,88	45,63,65,71	66,68,71,74	66,68,69,73	33,32,39,44
Od	0.2199	0.1898	0.1514	0.1309	0.1100	0.0874	0.6089

^Fungi: A–I: Alternaria padwicki, Botryodiplodia theobromae, Colletotrichum mause 75, Colletotrichum mause 246, Colletotrichum mause, Colletotrichum gloeosporiodes 282, Pestalotiposis guepini, Phytopohothora palmivora, Phytopohothora palmivora. ^Od: Optimum Dose.

Table IX.  In vitro inhibition of urease by compounds 1–7.

	IC50 ± Sem	IC50 ± Sem
Compound	(Bacillus pasteurii urease)	(Jack bean urease)
1	76.04 ± 0.77	88.35 ± 0.41
2	71.55 ± 0.81	85.36 ± 0.66
3	55.33 ± 0.72	58.22 ± 0.31
4	40.64 ± 0.31	42.03 ± 0.01
5	11.25 ± 0.04	22.28 ± 0.35
6	9.15 ± 0.25	10.23 ± 0.11
7	66.92 ± 0.31	89.74 ± 0.04
Thiourea (Standard)	16.07 ± 0.78	22.35 ± 0.13

Standard mean error of 3–5 assays. All the IC₅₀ values are in μM.

Figure 2 Dependence of in vitro anti-tumour ID₅₀ on percent CH for complexes 1–6.

Figure 3 Dependence of in vitro anti-tumour ID₅₀ on partition coefficients of complexes 1–6.