Metal-based new sulfonamides: Design, synthesis, antibacterial, antifungal, and cytotoxic properties

Figures & data

Scheme 1.  Preparation of ligands (L1)–(L3).

Table 1.  Physical measurements and analytical data of the metal (II) complexes, (1)–(12).

Compd.	Formula	[MW] (g/mole)	Yield (%)	MP (°C)	Elemental analysis
					C	H	N
(1)	[Co(L^1-H)2(H2O)2] C26H24N4O8S2Cl2Co	[714.46]	80	224–226	43.71 (43.78)	3.39 (3.45)	7.84 (7.79)
(2)	[Ni(L^1-H)2(H2O)2] C26H24N4O8S2Cl2Ni	[714.22]	82	230–232	43.72 (43.26)	3.39 (3.72)	7.48 (7.52)
(3)	[Cu(L^1-H)2(H2O)2] C26H24N4O8S2Cl2Cu	[719.07]	85	202–204	43.43 (43.41)	3.36 (3.39)	7.79 (7.80)
(4)	[Zn(L^1-H)2(H2O)2] C26H24N4O8S2Cl2Zn	[720.93]	81	241–243	43.32 (43.39)	3.36 (3.38)	7.77 (7.72)
(5)	[Co(L^2-H)2(H2O)2] C34H30N6O10S2Cl2 Co	[876.60]	81	232–234	46.58 (46.81)	3.45 (3.34)	9.59 (9.62)
(6)	[Ni(L^2-H)2(H2O)2] C34H30N6O10S2Cl2 Ni	[876.36]	80	226–228	46.60 (46.79)	3.45 (3.31)	9.59 (9.65)
(7)	[Cu(L^2-H)2(H2O)2] C34H30N6O10S2Cl2 Cu	[881.22]	82	248–250	46.34 (46.40)	3.43 (3.32)	9.54 (9.61)
(8)	[Zn(L^2-H)2(H2O)2] C34H30N6O10S2Cl2 Zn	[883.08]	85	245–247	46.25 (46.46)	3.42 (3.40)	9.52 (9.56)
(9)	[Co(L^3-H)2(H2O)2] C30H32N4O8S2Cl2 Co	[770.56]	82	202–204	46.76 (46.63)	4.19 (4.22)	7.27 (7.21)
(10)	[Ni(L^3-H)2(H2O)2] C30H32N4O8S2Cl2 Ni	[770.32]	78	218–220	46.78 (46.65)	4.19 (4.15)	7.27 (7.29)
(11)	[Cu(L^3-H)2(H2O)2] C30H32N4O8S2Cl2 Cu	[775.18]	80	212–214	46.48 (46.41)	4.16 (4.19)	7.23 (7.28)
(12)	[Zn(L^3-H)2(H2O)2] C30H32N4O8S2Cl2 Zn	[777.04]	81	226–228	46.37 (46.32)	4.15 (4.18)	7.21 (7.26)

Table 2.  Conductivity, magnetic and spectral data of the metal (II) complexes (1)–(12).

Compd.	WM (W^−1 cm^2 mol^1)	B.M (meff)	λmax (cm^−1)	Selected IR ν(cm^−1)
				C=N	C-O	SO2	S-N	C-S	M-N	M-O
(1)	46.5	4.98	7409;17,451; 20,589;29,321	1571	1395	1345, 1110	955	844	440	526
(2)	51.6	3.42	10,398; 15,709; 26,457; 29,878	1565	1395	1345, 1110	955	844	439	538
(3)	44.5	1.91	14,998; 19,166; 30,379	1566	1395	1345, 1110	955	844	438	532
(4)	48.2	Dia	28,939	1568	1395	1345, 1110	955	844	442	528
(5)	46.7	4.89	7368; 17,519; 20,646; 29,359	1569	1395	1345, 1110	955	844	442	535
(6)	50.2	3.37	10,448; 15,789; 26,498; 30,956	1570	1395	1345, 1110	955	844	438	534
(7)	43.2	1.86	15,158; 19,209; 30,357	1571	1395	1345, 1110	955	844	442	525
(8)	47.6	Dia	29,128	1568	1395	1345, 1110	955	844	439	538
(9)	46.8	4.96	7296; 17,498; 20,508; 29,373	1569	1395	1345, 1110	955	844	441	529
(10)	49.1	3.35	10,409; 15,695; 26,538; 29,996	1570	1395	1345, 1110	955	844	438	537
(11)	44.6	1.84	14,984; 19,184; 30,387	1566	1395	1345, 1110	955	844	441	535
(12)	49.1	Dia	28,985	1568	1395	1345, 1110	955	844	439	528

Note: Spectroscopic characterization of compounds.

Scheme 2.  Proposed structure of the metal(II) complexes, (1)–(12).

Table 3.  Antibacterial bioassay of ligands and metal (II) complexes.

Bacteria	Compound [zone of inhibition (mm)]*
	(L^1)	(L^2)	(L^3)	(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)	(9)	(10)	(11)	(12)	SD
Gram-negative
(a)	18	14	19	19	16	14	22	17	16	21	24	19	21	20	26	30
(b)	07	09	07	11	12	13	19	10	11	10	16	10	11	10	15	24
(c)	15	13	15	18	16	17	23	17	18	16	22	17	18	20	24	26
(d)	14	13	11	16	19	16	24	19	20	19	24	19	17	18	25	27
Gram-positive
(e)	18	17	18	21	18	17	22	20	19	19	25	17	20	18	26	30
(f)	17	16	20	20	17	18	25	18	20	18	24	20	19	22	25	28
SDDEV	4.2	2.8	5.1	3.6	2.4	1.9	2.1	3.5	3.4	3.9	3.3	3.6	3.6	4.2	4.2	1.7

Note: (a) = E. coli (b) = S. flexenari (c) = P. aeruginosa (d) = S. typhi (e) = S. aureus (f) = B. subtilis 10<: weak; >10: moderate; > 16: Significant SD = standard drug (Imipenum); STDEV = standard deviation; *: concentration used 1 mg/mL in DMSO.

Figure 1.  Comparison of antibacterial activity of ligands (L¹)–(L³) and their complexes (1)–(12).

Figure 2.  Comparison of antifungal activity of ligands (L¹)–(L³) and their complexes (1)–(12).

Table 4.  Antifungal bioassay (concentration used 200 µg/mL) of ligands and metal (II) complexes.

Organism	Compound [zone of inhibition (mm)]
	(L^1)	(L^2)	(L^3)	(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)	(9)	(10)	(11)	(12)	SD
(a)	83	79	00	38	42	25	51	67	65	00	81	39	48	31	76	A
(b)	46	00	47	33	64	48	00	31	71	62	68	61	60	59	00	B
(c)	31	76	53	00	59	52	55	48	44	00	49	42	66	51	82	C
(d)	65	00	64	00	38	89	00	87	86	71	00	48	58	84	50	D
(e)	58	72	34	90	68	75	00	58	39	48	00	37	82	86	88	E
(f)	00	24	37	39	00	85	67	00	78	00	72	00	48	46	55	F
STD.	37.9	21.3	23.5	29.9	28.8	22.6	29.4	32.1	22.6	39.3	29.4	26.5	13.7	18.2	32.3	—

Note: (a) =T. longifucus (b) =C. Albicans (c) = A. flavus (d) =M. canis (e) =F. Solani (f) =C. glaberata SD = standard drugs MIC µg/mL; A = Miconazole (70 µg/mL:1.6822 × 10^−-7 M/mL),B = Miconazole (110.8 µg/mL:2.6626 × 10⁻⁷ M/mL), C = Amphotericin B (20 µg/mL:2.1642 × 10⁻⁸ M/mL), D = Miconazole (98.4 µg/mL:2.3647 × 10⁻⁷ M/mL), E = Miconazole (73.25 µg/mL: 1.7603 × 10⁻⁷ M/mL), F = Miconazole (110.8 µg/mL: 2.66266 × 10⁻⁷ M/mL); STD = standard deviation.

Table 5.  Brine Shrimp bioassay data of the ligands (L¹)–(L³) and their complexes (1)–(12).

Compd.	Gram-negative			Gram-positive		LD50 (M/mL)
	E. coli	P. aeruginosa	S. typhi	S. aureus	B. subtilis
(L^1)	—	—	—	—	—	> 2.981 × 10^−3
(L^2)	—	—	—	—	—	> 3.126 × 10^−3
(L^3)	—	—	—	—	—	> 3.105 × 10^−3
(1)	—	—	—	—	—	> 1.489 × 10^−3
(2)	—	—	—	—	—	> 1.524 × 10^−3
(3)	—	—	—	—	—	0.5986 × 10^−3
(4)	—	4.172 × 10^−8	2.916 × 10^−8	1.729 × 10^−7	4.178 × 10^−8	> 1.615 × 10^−3
(5)	—	—	—	—	—	> 1.365 × 10^−3
(6)	—	—	—	—	—	> 1.492 × 10^−3
(7)	—	—	—	—	—	0.6129 × 10^−3
(8)	1.479 × 10^−7	2.034 × 10^−8	4.102 × 10^−8	6.219 × 10^−8	2.145 × 10^−8	> 1.532 × 10^−3
(9)	—	—	—	—	—	> 1.327 × 10^−3
(10)	—	—	—	—	—	> 1.467 × 10^−3
(11)	—	—	—	—	—	0.6238 × 10^−3
(12)	5.927 × 10^−8	2.987 × 10^−8	1.468 × 10^−8	1.484 × 10^−7	6.595 × 10^−8	> 1.389 × 10^−3

Note: The compound (3) showed activity (LD₅₀ = 5.986 × 10⁻⁴ M/mL), compound (7) showed activity (LD₅₀ = 6.129 × 10⁻⁴ M/mL) and compound (11) showed activity (LD₅₀ = 6.238 × 10⁻⁴ M/mL) in the present series of compounds. It was interesting to note that only copper complexes showed potent cytotoxicity whereas the other metal complexes did not. This activity relationship may help to serve as a basis for future direction towards the development of certain cytotoxic agents for clinical applications.