Synthesis, characterization, antimicrobial activity and structure–activity relationships of new aryldisulfonamides

Figures & data

Figure 1.  Synthesis of the compounds.

Table 1.  The ¹H NMR data of the compounds (for half of molecules).

Assignment	(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)
<CH3>	2.39(s,3H)	2.36(s,3H)	2.35(s,3H)	2.38(s,3H)	3.85(s,3H)	3.84(s,3H)	3.83(s,3H)	3.82(s,3H)
NH<CH2>	2.71(t,2H)	2.72(t,2H)	2.74(s,2H)	2.75(t,2H)	2.71(s,3H)	2.72(t,2H)	2.72(s,3H)	2.73(t,2H)
NHCH2<CH2>	-	1.61(m,2H)	1.59(m,2H)	1.53(m,2H)	-	1.62(m,2H)	1.50(m,2H)	1.55(m,2H)
NHCH2CH2 <CH2>	-	-	-	1,24(m,2H)	-	-	-	1,22(m,2H)
Ar	7.60(m,4H)	7.60 (m,4H)	7.55 (m,4H)	7.53(m,4H)	7.66(m,4H)	7.68(m,4H)	7.68(m,4H)	7.64(m,4H)
SO2<NH>	4.62 (s)	4.64(s)	4.65(s)	4.75(s)	4.84 (s)	4.98 (s)	5.00(s)	5.02(s)

Table 2.  The ¹³C NMR data of the compounds.

Assignment	(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)
<CH3>	21.39	20.19	20.89	20.89	55.58	56.56	55.78	56.83
NH<CH2>	29.84	42.15	42.05	42.32	42.10	47.18	45.28	46.34
NHCH2<CH2>	-	21.14	26.13	28.43	-	22.20	27.80	29.70
NHCH2CH2 <CH2>	-	-	-	23.13	-	-		23.35
Ar<CH>	126.65	126.99	126.44	126.44	114.31	114.45	112.77	113.33
	129.77	130.12	129.53	129.52	128.56	128.40	127.62	126.55
	138.02	137.38	137.64	137.72	131.85	135.50	133.75	134.55
	143.00	142.68	142.43	142.17	162.15	160.33	159.55	159.66

Table 3.  Wavenumber (cm⁻¹) of selected vibration of the compounds.

Comp.	υNH	δNH	υ(CH3)	υas(SO2)	υs(SO2)
(1)	3288(m)^a	1458(m)	2940(m)	1336(s)^b	1162(m)
(2)	3285(m)	1439(m)	2973(m)	1329(s)	1162(m)
(3)	3291(m)	1426(m)	2954(m)	1329(s)	1162(m)
(4)	3288(m)	1420(m)	2960(m)	1336(s)	1157(m)
(5)	3294(m)	1484(m)	2979(m)	1343(s)	1162(m)
(6)	3296(m)	1452(m)	2980(m)	1345(s)	1160(m)
(7)	3292(m)	1447(m)	2960(m)	1332(s)	1162(m)
(8)	3290(m)	1466(m)	2979(m)	1345(s)	1152(m)

^a m: medium, ^b s: strong

Table 4.  Antimicrobial activity of compounds with microdilution method.

Comp.	MIC (µg/mL)
	E.coli ATCC 11230	S. enterititis ATCC 13076	B. magaterium RSKK 5117	B. cereus ATCC 6633	S. aureus ATCC 25953
(1)	110	110	368	147	147
(2)	115	153	383	156	192
(3)	125	277	415	177	217
(4)	285	328	440	290	410
(5)	100	100	303	140	134
(6)	110	140	322	148	180
(7)	120	263	356	164	208
(8)	275	312	394	282	390
(9)	42	42	117	59	59

Table 5.  Result of the antimicrobial test of compounds (disc potency 60 µg).

Compound	Diameter of inhibition zone (mm)
	Ec	Se	Bm	Bc	Sa
(1)	18	17	8	14	15
(2)	17	16	-	13	13
(3)	15	11	-	12	11
(4)	13	11	-	11	10
(5)	20	20	9	16	17
(6)	19		-	14	15
(7)	18	20	-	13	13
(8)	16		-	11	10
(9)	24	23	-	21	20
ciprofloxacin (5 μg)	38	31	15	27	29

Ec, Escherichia coli; Se, Salmonella enterititis; Bm, Bacillus magaterium; Bc, Bacillus cereus; Sa, Staphylococcus aureus.

Table 6.  Calculated partition coefficients and aqueous solubility of the compound studied.

Comp.	AlogPs	AC logP	AB/logP	AlogPS	AC logS	AB/logS	AB/pKa(acid)
(1)	0.78	1.84	2.76	-3.90(46.06 mg/L)	-2.64(0.84 g/L)	-3.59(94.72 mg/L)	-
(2)	0.98	2.31	3.73	-4.17(25.71 mg/L)	-2.91(0.47 g/L)	-3.86(52.81 mg/L)	-
(3)	1.28	2.77	3.86	-4.49(12.71 mg/L)	-3.18(0.26 g/L)	-3.95(44.50 mg/L)	-
(4)	1.61	3.24	4.42	-4.78(6.84 mg/L)	-3.45(0.15 g/L)	-3.84(59.35 mg/L)	-
(5)	0.97	1.00	2.23	-3.55(0.11mg/L)	-1.99(4.10 g/L)	-3.82(60.62 mg/L)	9.70
(6)	0.86	1.47	3.19	-3.80(64.96 mg/L)	-2.26(2.28 g/L)	-4.05(36.95 mg/L)	9.70
(7)	1.04	1.93	3.32	-4.01(41.46mg/L)	-2.53(1.26 g/L)	-4.13(31.77mg/L)	9.70
(8)	1.39	2.40	3.89	-4.30(22.28mg/L)	-2.80(0.70 g/L)	-4.13(32.81mg/L)	9.70
(9)	0.26	-0.42	0.53	-1.21(10.69 g/L)	-0.18(0.11kg/L)	-1.59(4.43g/L)	6.20
dichlorophenamide	0.95			-2.87(0.41 g/L)			7.8
sulfanilamide	-0.16^a			-1.21(10.52 g/L)			10.1

^a Experimental result is -0.62.

Table 7.  Antimicrobial activity of compounds and regression coefficient.

Comp.	log(1/MIC)
	Ec	Se	Bm	Bc	Sa
(1)	3.53	3.53	3.00	3.40	3.40
(2)	3.52	3.40	2.99	3.39	3.30
(3)	3.50	3.16	2.98	3.35	3.26
(4)	3.16	3.10	2.97	3.15	3.00
(5)	3.60	3.60	3.12	3.47	3.48
(6)	3.58	3.47	3.11	3.45	3.36
(7)	3.55	3.21	3.08	3.42	3.31
(8)	3.21	3.15	3.05	3.20	3.05
(9)	3.65	3.65	3.20	3.50	3.50
Regression coefficient
AlogPs	0.89	0.90	0.65	0.91	0.92
AC logP	0.75	0.85	0.85	0.83	0.85
AB/logP	0.75	0.88	0.66	0.81	0.90
AlogPs	0.78	0.88	0.79	0.85	0.87
AC logS	0.69	0.78	0.91	0.78	0.77
AB/logS	0.15	0.52	0.41	0.13	0.33

Ec, Escherichia coli; Se, Salmonella enterititis; Bm, Bacillus magaterium; Bc, Bacillus cereus; Sa, Staphylococcus aureus.

Table 8.  Some physicochemical properties of compounds.

Comp.	MW	MV	TPSA	MR	HOMO	LUMO	Dμ
(1)	368.47	1054.17	109.1	94.34	-10.0897	-0.7508	8.84
(2)	382.49	1091.78	109.1	99.20	-10.0761	-0.7106	8.66
(3)	396.52	1161.02	109.1	103.85	-10.0538	-0.6770	1.69
(4)	410.55	1206.93	109.1	108.45	-9.9880	-0.6745	8.94
(5)	400.46	1087.96	110.8	97.18	-9.8396	-0.6903	8.01
(6)	414.49	1126.74	110.8	102.05	-9.8250	-0.6354	7.66
(7)	428.52	1192.96	110.8	106.69	-9.8173	-0.8732	7.97
(8)	442.55	1231.82	110.8	111.29	-9.8101	-0.8041	8.28
(9)	186.23	555.60	74.19	47.74	-9.3952	-0.7776	6.14
Regression coefficient (r)
Ec	0.442	0.720	0.180	0.734	0.015	0.083	0.197
Se	0.556	0.897	0.165	0.887	0.023	0.280	0.297
Bm	0.428	0.077	0.929	0.081	0.850	0.115	0.212
Bc	0.379	0.714	0.286	0.724	0.090	0.060	0.093
Sa	0.512	0.822	0.193	0.844	0.011	0.107	0.055

MW, molecular weight; MV, molecular volume; TPSA, topological polar surface area;

MR, molecular refractivity.