Novel Synthesis and Biological Evaluation of some New Bipyrazolyl Benzenesulfonamides as possible Antimicrobial and Chemotherapeutic Agents

Dilesh Indorkar*, O.P. Chourasia and S.N. Limaye

Department of Chemistry, Dr. H.S. Gour Central University, Sagar (M.P.) 470 003

*Corresponding Author E-mail: dileshindorkar@yahoo.in

ABSTRACT:

A series of functionalized bipyrazoles, fused bipyrazoles and other related heterocyclic systems have been synthesized.The key intermediate bipyrazoles have been prepared by cyclocondensation of the appropriate chalcone with4-hydrazinobenzenesulfonamide hydrochloride. The chemistry of the reactions employed in the synthesis of the target compounds together with their chemical behaviour, are discussed and the structures of the newly synthesized compounds have been confirmed by the IR and 1H and 13C NMR spectral data. All the synthesized compounds show weak anticancer activity and weak antimicrobial and antifungal activity against some bacteria and fungi.

KEY WORDS: Pyrazoles, bipyrazoles, bipyrazole benzensulfonamides, thiazolidines

INTRODUCTION:

Pyrazoles and their related fused heterocycles have attracted attention of organic chemists very much due to their biological and chemotherapeutic importance. These compounds are of interest as potential prototypes for various enzyme inhibitors such as COX-2 , p38 MAP kinase3, and CDK2/Cyclin A inhibitory activities4. In addition, many pyrazole derivatives have shown significant pharmacological interest as antianxiety5, antipyretic, analgesic and anti-inflammatory drugs6-7.Moreover, they are well known for their remarkable antimicrobial8-9, antiparasitic10-11 and anticancer12-13 activities. Prompted by these facts, and in continuation of our ongoing studies on novel biologically active molecules14-16, it was considered worthwhile to synthesize some new pyrazole-pyrazoline derivatives, bearing functionalities that are reported to exhibit possible chemotherapeutic and antimicrobial activities. They are sulphonamide, sulfonylurea and thiourea groups. Some target compounds were planned to comprise heterocyclic rings that are known to possess high antibacterial and/or anticancer activities such as the thiazole and the thiazine ring systems.

The structures of the newly synthesized compounds were elucidated with elementary microanalyses and substantiated with IR and 1H and 13 C NMR data. The target compounds have been subjected to the National Cancer Institute NCI in vitro disease-oriented human cells screening panel assay, Maryland, USA, to screen for their anticancer activity 17. In addition, the in vitro antibacterial and antifungal activities of the target compounds were performed using the Agar diffusion method18

RESULTS AND DISCUSSION:

The synthetic strategies adopted for the preparation of the intermediate and target products are depicted in Schemes I-III. The starting chalcones 2-4 were obtained by condensing equimolar amounts of the appropriate ketone with 1-phenylpyrazole-4-carbox- aldehyde 1, in an aqueous ethanolic solution of sodium hydroxide. The IR spectra of the prepared chalcones, 2-4 showed a carbonyl absorption in the region 1658-1667 cm-1 which is characteristic of the carbonyl group as well as an olefinic C=C bond in the region 1604-1611 cm-1. The electronic spectra exhibited two absorption maxima in the regions 234-270 and 294-320 nm. The 1H NMR spectra of 5 and 6 showed the olefinic protons, H-α and H-β, as two doublets (J = 16 Hz) at δ6.62-6.67 and 7.54-7.58 respectively. Cyclocondensation of the above chalcones 2-4 with 4-hydrazinobenzene-sulfonamide hydrochloride  afforded the corresponding pyrazoline 5-7 (Table I).Their IR spectra revealed two peaks at 3355-3378 and 3240-3264 cm-1 due to NH2 group and two peaks at 1330-1350 and 1170-1185 cm-1 for SO2N function. Mild oxidation of the pyrazoline derivatives 5-7 with bromine water yielded the corresponding pyrazoles 8- 10. In agreement with the suggested structures, the 1H NMR spectra of the pyrazoline derivatives 5 and 6 exhibited beside the aromatic protons, two multiplets at δ 5.10-5.32 and 2.98-3.24. The low field multiplet is assigned to H-5 of the pyrazoline while the other multiplet is attributed to H-4 (Table II). protons a doublet at δ 5.56 for H-3 and a multiplet at δ 3.62 for H-3a. Spectra of the pyrazole derivatives 8-10 displayed signals due to aromatic and aliphatic protons but lacked signals characteristic of H-3, H-3a, H-4 and H-5 of the corresponding pyrazolines (Tables II). The structures of the above compounds 5-10 were further confirmed from their 13C NMR data (Table III). Addition of pyrazolines 5-7 across the N=C bond of the appropriate isocyanate and isothiocyanate in dry acetone yielded the corresponding benzene- sulfonylureas 11, 12, 19 and thioureas 13, 14, 20 respectively. The IR spectra of these compounds exhibited two absorptions at 1338-1365 and 1168-1182 cm-1 for the SO2N group and a urea carbonyl band at 1642-1658 cm-1 in case of compounds 11, 12,19 and a thiourea carbonyl absorption at 1155-1160 cm-1 in case of compounds 12, 13, 20.

Their 1H and 13   C NMR data are recorded in Tables II-III Cyclization of the thiourido group of compounds13, 14, 20 by treatment with ethyl bromoacetate and afforded the corresponding 4-oxothiazoline and thiazoline derivatives 15, 16, 21and 17, 18, 22 respectively.

IR spectra of 15, 16, and 21 showed cyclic carbonyl absorption at 1722-1730and two peaks at 1335-1364 and 1172-1185 cm-1 for the SO2N group. The structures of the above compounds 15-22 were supported by their 1H and 13CNMR data (Tables II-III). The spectral data are inadequate to show the α or βconfiguration of the 3-(pyrazol-4-yl) group in compounds 7, 19-22.

EXPERIMENTAL:

Melting points were determined in open glass capillaries, on a Gallenkamp melting point apparatus, and were uncorrected. The IR spectra were taken as Shimadzu 260 spectrometer. The 1H NMR and13   C NMR spectra were recorded on Bruker DPX-400-FT spectrometer using a mixture of CDCl3 and DMSO-d6 as the solvent, tetramethylsilane as the internal standard and chemical shifts in (δ, ppm).Splitting patterns were designated as follows: s:singlet; d: doublet; m: multiplet. Follow up of the reactions and checking the purity of the compounds were made by TLC on silica gel-protected aluminum sheets (Type 60 F254, Merck) and the spots were detected by exposure to UV-lamp at λ 254.The starting chalcones 2-4 was prepared according to a literature procedure41.KBr disk on a Nicolet Magna 520 FT- IR spectro-photometer. (Scheme-I).

Scheme I

General procedure for preparation of chalcones, 2-4

A solution of the 1-phenylpyrazole-4-carbox-aldehyde 1 (1.72 g, 0.01 mol) in ethanol (20 mL) was added to a stirred solution of the appropriate ketone (0.01mol) in ethanolic KOH (20%, 20 mL), and stirring was maintained at RT for 6 hr. The reaction mixture was then poured onto water (200 mL) and set a side for an overnight. The precipitated solid product was collected by filtration, washed with water, dried and recrystallized from ethanol. IR: 1658-1667 (C=O), 1604-1611 cm-1 (C=C).

3-(1-Phenyl-1H-pyrazol-4-yl)-1-(thiophen-2-yl)-prop-2-en-1-one, 2:

1H NMR (DMSO-d6,CDCl3): δ6.67 (d, 1H, H-α), 7.54 (d, 1H, H-β), 7.06-7.92 (m,10H, Ar-H); 13C NMR: δ 129.3 (C- α), 142.8 (C- β),107.2, 118.8, 126.0, 126.3, 128.5, 129.1, 135.6, 136.6,139.8, 141.5, 145.7 (Ar-C), 180.7 (C=O).

1-(Furan-2-yl)-3-(1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-one, 3:

1H NMR (DMSO-d6,CDCl3): δ 6.62 (d,1H, H-α), 7.58 (d, 1H, H-β), 6.61-7.85 (m, 10H,Ar-H).

2-Methyl-6-((1-phenyl-1H-pyrazol-4-yl)methyl-ene)cyclohexanone, 4:

1H NMR (CDCl3): δ 1. 21(d,3H, CH3), 1.32-1.96 (m, 6H, H-3, 4, 5), 2.52 (m, 1H,H-6), 7.26 (s, 1H, olefinic-H), 7.33-7.96 (m, 7H, Ar-H); 13C NMR: δ 13.7 (CH3), 27.3, 27.4, 33.2, 46.7(cyclohexyl-C), 107.5, 118.3, 125.8, 126.6, 129.4,139.8, 141.4 (Ar-C), 131.6 (olefinic-C)

4-[(3-(2-Thienyl)-5-(1-phenylpyrazol-4-yl)-4,5-di-hydropyrazol-1-yl]benzenesulfonamide,5,6 and 4-[7-methyl-3-(1-phenylpyrazol-4-yl)-3,3a,4,5,6,7-hexahydroindazol-2-yl]benzenesulfonamide, 7

A solution of the appropriate chalcones (2-4,0.02 mol) in ethanol (25 mL) was refluxed with

p-hydrazinobenzene sulfonamide hydrochloride (4.9 g,0.022 mol) for 4 hr. On concentration, the separated product was filtered, washed with cold ethanol and recrystallized from a mixture of benzene-ethanol(1:1).

4-[(3-(2-Thienyl)-5-(1-phenylpyrazol-4-yl)pyrazol-1-]benzenesulfonamide8,9 and 4-[7-methyl-3-(1-phenylpyrazol-4-yl)4,5,6,7-hexahydroindazol-2-l]benzenesulfonamide,10

To a stirred suspension of the appropriate pyra-zoline derivative (0.01 mol) in water (10 mL),bromine water (5%, 15 mL) was gradually added over a period of 30 min at 25°C. After stirring for 3 hr atRT, the pyrazole derivatives thus formed, were collected by filtration, thoroughly washed with waterand dried. They were recrystallized from ethanol.

N1-[4-[(3-(2-Thienyl)-5-(1-phenylpyrazol-4-yl)-4,5-dihydropyrazol-1-yl]benzenesulfonyl]-N3-substi-tuted ureas 11, 12 and N1-[4-(7-methyl-3-(1-phenylpyrazol-4-yl)-3,3a,4,5,6,7-hexahydroindazol-2-l)benzensulfonyl] N3-substituted ureas, 19

A mixture of the appropriate pyrazolines 5, 6 or 7(0.01 mol) and anhydrous KCO3 (2.8 g, 0.02 mol) in dry acetone (25 mL) was heated under reflux withstirring with the appropriate isocyanate (0.011 mol) for 18 hr. The solvent was removed under reduced pressure and the remaining solid residue was dissolved in water (30 mL). After acidification of the resulting solution with 2N HCl, the precipitated crude product was filtered, washed with water, dried and recrystallized from ethanol. (Scheme II)

N1-[4-[(3-(2-Thienyl)-5-(1-phenylpyrazol-4-yl)-4,5-dihydropyrazol-1-yl]benzenesulfonyl]-N3-substitu-ted thioureas 13, 14 and N1-[4-(7-methyl-3-(1-phenylpyrazol-4-yl)-3,3a,4,5,6,7-hexahydroindazol-2-yl)benzensulfonyl]N3-substituted thioureas, 20

A solution of the appropriate isothiocyanate (0.011 mol) in dry acetone (5 mL) was added to a stirred mixture of the suitable pyrazoline (0.01 mol) and anhydrous KCO3 (2.8 g, 0.02 mol) in dry acetone (25 mL), and the reaction mixture was heated underreflux with stirring for 10 hr. The solvent was removed under reduced pressure and the remaining solid residue was dissolved in water (30 mL) and acidified with 2N HCl. The precipitated crude product was filtered, washed with water, dried and recrystal-lized from ethanol.

2-[4-[(3-(2-Thienyl)-5-(1-phenylpyrazol-4-yl)-4,5-dihydropyrazol-1-yl)benzenesulfonylimino]-3-sub-stituted thiazolidin-4-ones 15,16 and 2-[4-(7-methyl-3-(1-phenylpyrazol-4-yl)-3,3a,4,5,6,7-hexahydro-indazol-2-yl)benzenesulfonylimino]-3-substitutedthiazolidin-4-ones, 21

To a solution of the appropriate thiourea derivatives 13, 14 or 20 (0.01 mol) in absolute ethanol (20 mL) was added ethyl bromoacetate (1.84 g, 0.011mol) and anhydrous sodium acetate (1.64 g, 0.02 mol), and the reaction mixture was heated underreflux for 2 hr. The mixture was left to attain RT then poured into ice-cold water (30 mL), and the solid product thus formed was filtered, washed with water,dried and recrystallized from ethanol-benzene mixture(1:1).

2-[4-[(3-(2-Thienyl)-5-(1-phenylpyrazol-4-yl)-4,5-dihydropyrazol-1-yl)benzenesulfonylimino]-3-sub-stituted thiazolines 17, 18 and 2-[4-(7-methyl-3-(1-phenylpyrazol-4-yl)-3,3a,4,5,6,7-hexahydro-indaz-ol-2-yl)benzenesulfonylimino]-3-substituted thiazo-lidin-4-ones, 22

A solution of the appropriate thiourea derivative (0.01 mol) in absolute ethanol (20 mL) was refluxed with ω-bromoacetophenone (2.2 g, 0.0 11 mol) and anhydrous sodium acetate (1.64 g, 0.02 mol) for 3 hr during which the solid product was partially crystallized out. The mixture was left to attain RT then filtered, washed with cold ethanol, dried and recrystallized from ethanol.

Scheme II

Scheme III

Biological evaluation

All the newly synthesized target compounds have been subjected to the National Cancer Institute NCI in vitro disease-oriented human cells screening panel assay, Maryland, USA, to screen their anticancer activity. nfortunately, all of them showed weak anticancer activity (< 32% growth inhibition in the three cell line assay).

In addition, the in vitro antibacterial and antifungal activities of the target compounds were also tested using the Agar-diffusion method. Test organisms utilized were Staphylococcus aureus as an example of Gram positive bacteria, Escherichia coli and as an example of Gram negative bacteria and Candida albicans as representatives of fungi. None of the tested compounds were able to exert significant antibacterial or antifungal activities (Inhibition zone diameters < 10 mm).Scheme III

Table I Characterization dada of compounds 2-22

Compd	x	R or R'	yield	m.p.	mol.form.			Calcd%				Found%
						C	H	N	S	C	H	N	S
2	S		98	218	C16H12N2OS	68.55	4.31	9.99	11.44	68.65	4.32	10.01	11.46
3			95	202	C16H12N2O2	72.72	4.58	10.61		72.87	4.69	4.59
4			97	115	C17H18N2O	76.66	6.81	10.52		76.75	6.92	10.62
5	S		92	204	C22H19N5O2S2	58.78	4.26	15.58	14.27	58.87	4.32	15.67	14.33
6	O		90	223	C22H19N5O3S	60.96	4.42	16.16	7.41	61.02	4.43	16.18	7.32
7			94	207	C23H25N5O2S	63.43	5.79	16.08	7.36	63.55	5.87	16.14	7.46
8	S		82	168	C22H17N5O2S2	59.04	3.83	15.65	14.33	59.18	3.96	15.64	14.32
9	O		80	134	C22H17N5O3S	61.24	3.97	16.23	7.43	61.41	4.02	16.35	7.42
10			84	165	C23H23N5O2S	63.72	5.35	16.15	7.41	63.85	5.51	16.18	7.34
11a	S	Cyclohexyl	79	197	C29H30N6O3S2	60.61	5.26	14.62	11.16	60.72	5.34	14.52	11.26
11b	S	Ph	82	235	C29H24N6O3S2	61.25	4.25	14.78	11.28	61.35	4.28	14.82	11.31
11c	S	p-ClC6H4	84	253	C29H23ClN6O3S2	57.75	3.84	13.93	10.63	57.86	3.96	13.88	10.78
12a	O	Cyclohexyl	80	202	C29H30N6O4S	62.35	5.41	15.04	5.74	62.53	5.52	15.15	5.85
12b	O	Ph	82	175	C29H24N6O4S	63.03	4.38	15.21	5.81	63.14	4.67	15.38	5.72
12c	O	p-ClC6H4	83	185	C29H23ClN6O4S	59.33	3.95	14.32	5.46	59.38	5.89	14.42	5.56
13a	S	CH3	82	200	C24H22N6O2S3	55.15	4.24	16.08	18.41	55.26	5.89	16.11	18.51
13b	S	Ph	79	170	C29H24N6O2S3	59.57	4.14	14.37	16.45	59.48	4.76	14.26	16.56
13c	S	p-ClC6H4	80	157	C29H23ClN6O2S3	56.25	3.74	13.57	15.54	56.36	4.43	13.68	15.71
13d	S	p-FC6H4	76	143	C29H23FN6O2S3	57.79	3.85	13.94	15.96	57.89	6.76	14.05	16.12
14a	O	CH3	78	219	C24H22N6O3S2	56.91	4.38	16.59	12.66	56.94	4.56	16.68	12.76
14b	O	Ph	82	145	C29H24N6O3S2	61.25	4.25	14.78	11.28	61.41	4.98	14.87	11.35
14c	O	p-ClC6H4	83	172	C29H23ClN6O3S2	57.75	3.84	13.93	10.63	57.91	4.64	14.05	10.64
14d	O	p-FC6H4	72	148	C29H23FN6O3S2	59.37	3.95	14.33	10.93	59.36	4.56	14.38	11.02
15a	S	Ph	76	222	C31H24N6O3S3	59.61	3.87	13.45	15.41	59.52	3.54	13.56	15.36
15b	S	p-ClC6H4	77	245	C31H23ClN6O3S3	56.48	3.52	12.75	14.59	56.49	4.12	12.91	14.68
15c	S	p-FC6H4	74	198	C31H23FN6O3S3	57.93	3.61	13.08	14.97	58.13	4.23	13.12	15.02
16a	O	CH3	76	228	C26H22N6O4S2	57.13	4.06	15.37	11.73	57.24	3.43	15.48	11.88
16b	O	Ph	77	186	C31H24N6O4S2	61.17	3.97	13.81	10.54	61.17	5.34	13.92	10.65
16c	O	p-ClC6H4	78	243	C31H23ClN6O4S2	57.89	3.61	13.07	9.97	58.01	4.23	13.17	9.82
17a	S	Ph	74	225	C37H28N6O2S3	64.89	4.12	12.27	14.05	64.97	6.45	12.41	14.15
17b	S	p-ClC6H4	72	217	C37H27ClN6O2S3	61.78	3.78	11.68	13.37	61.86	4.54	11.72	13.47
17c	S	p-FC6H4	70	214	C37H27FN6O2S3	63.23	3.87	11.96	13.69	63.41	4.54	12.02	13.72
18a	O	CH3	70	248	C32H26N6O3S2	63.35	4.32	13.85	10.57	63.36	4.34	13.91	10.67
18b	O	Ph	71	256	C37H28N6O3S2	66.45	4.22	12.57	9.59	66.56	4.23	12.62	9.68
18c	O	p-ClC6H4	73	224	C37H27ClN6O3S2	63.19	3.87	11.95	9.12	63.28	4.23	12.06	9.22
18d	O	p-FC6H4	70	210	C37H27FN6O3S2	64.71	3.96	12.24	9.34	64.85	4.34	12.35	9.45
19a		Cyclohexyl	75	204	C30H36N6O3S	64.26	6.47	14.99	5.72	64.36	4.54	15.11	5.68
19b		Ph	78	222	C30H30N6O3S	64.96	5.45	15.15	5.78	65.12	5.45	15.2	5.77
19c		p-ClC6H4	76	236	C30H29ClN6O3S	61.16	4.96	14.27	5.44	61.26	4.34	14.31	5.45
20a		CH3	72	195	C25H28N6O2S2	59.03	5.55	16.52	12.61	59.04	4.54	16.62	12.67
20b		C4H9	70	156	C28H34N6O2S2	61.06	6.22	15.26	11.64	61.17	4.54	15.27	10.72
20c		p-ClC6H4	76	190	C30H29ClN6O2S2	59.54	4.83	13.89	10.61	59.68	4.65	13.98	10.88
20d		p-FC6H4	70	221	C30H29FN6O2S2	61.21	4.97	14.28	10.89	61.38	4.65	14.34	11.77
21a		CH3	72	247	C27H28N6O3S2	59.11	5.14	15.32	11.69	59.24	4.54	15.36	11.72
21b		p-ClC6H4	74	272	C32H29ClN6O3S2	59.57	4.53	13.03	9.94	59.68	4.65	13.11	9.91
21c		p-FC6H4	70	230	C32H29FN6O3S2	61.13	4.65	13.37	10.21	61.28	4.54	13.31	10.23
22a		CH3	72	237	C33H32N6O2S2	65.11	5.31	13.81	10.53	65.12	4.76	13.92	10.64
22b		p-ClC6H4	74	258	C38H33ClN6O2S2	64.71	4.72	11.92	9.09	64.82	4.43	12.11	9.21
22c		p-FC6H4	71	224	C38H33FN6O2S2	66.26	4.83	12.21	9.3	66.37	4.65	12.37	9.44

Table II  1H NMR Spectral data (δ/ppm) of pyrazoline pyrazole derivatives

Compd	X	R or R'	m.2H	m.1H	m.	S.1H		CH2
			H-4	H-5	Ar-H	NH	CH3 and/or CH2
5	S		3.76	5.12	6.98
6	O		3.66		6.34
8	S		3.45		7.01
9	O		3.67	5.22	6.98
11a	S	cyclohexyl	3.32	5.12	6.76	8.43
11b	S	C6H5	3.87	532	6.23	8.43
11c	S	p-ClC6H4	3.36	5.76	6.09	8.23
11b	O	C6H4	3.65	5.87	6.98	8.65
12c	O	p-ClC6H4	3.87	5.12	6.45	8.98
13a	S	CH3	3.07	5.76	6.23	8.54	3.48
13b	S	C6H5	3.98	5.34	6.76	8.45
13c	S	p-ClC6H4	3.65	5.12	6.23	8.34
13d	S	p-Fc6H4	3.98	5.54	6.45	8.34
14a	O	CH3	3.12	5.26	6.34	8.34	3.39
14b	O	C6H5	3.34	5.87	6.45	8.34
14c	O	C6H5	3.24	5.12	6.23	8.98
15a	S	p-ClC6H4	3.45	5.56	7.09		4.46
15b	S	CH3	3.76	5.87	6.89		4.87
15c	S	C6H5	3.65	5.23	6.34		4.32
16a	O	p-ClC6H4	3.87	5.23	7.12		3.54
16b	O	CH3	3.87	5.54	7.54		4.55
17a	S	C6H5	3.87	5.45	6.23
17b	S	p-ClC6H4	3.23	5.23	6.23
18a	O	CH3	3.65	5.87	6.23		4.77
18b	O	C6H5	3.23	5.67	643
18c	O	p-ClC6H4	3.12	5.23	6.23
Solution in mixture of CDCL3 and DMSO d6

Table III -C13 NMR spectral data ( ppm) of some pyrazoline  pyrazole derivatives

Compd	x	R or R	C-4	C-5	Cyclohexyl	C-3a	C-	Ar-C	Other
5	S		39.8	50.9				112.6,118.2,118.8,125.6 126.1, 126.3,126.6,126.7,127.7 129.1,139.7, 140.3,,146.7,155.6
	O		37.9	48.4				110.3,112.8,117.1,125.4,126.1138.5, 140.3,143.2,11 156.3	19.8CH2
7					24.6,27.4	24.7	35.5	118.2,118,8,125.4,125.8,126.1129.1, 129.5,136.3,139.7140.3 140.9,154.7
8	S							112.8,118.5,119.2,121.9,125.2,125.8, 1265126.8127.4129.7 140.6,144.3,157.1
10					17.9.31.2, 32.1, 41.1			110.8,116.5,119.4,120.3122.3125.1, 139.3,140.4144.4	21.9CH2
11b	S	ph	38.4	50.2				113.4,117.6,118.6,119.4,125.2125.7, 126.2,126.5127.1127.8 128.4,129.3,129.6,136.4,142.4 145.2,155..8	176.2CO
11c	S	p-ClC6H6	39.3	51.1				112.8,,116.7,118.3,119.6,125.1125.6, 1236.3,127.9,129.4,129.8133.2,136.7,139.6,143.3,166.4 156.3	172.9CO 124.9
12b	O	ph	49.8	38.8				110.6,112.7,117.3,118.9, 120.4122.3,125.5, 117.3,118.9,120.4 129.3,139.4,140.2,144.6,155.2
13a	S	CH3	40.1	50.3				112.9,116.9,118.2,120.1, 125.2125.8,126.8,127.6,127.6,129.8 134.4,136.2,139.7,142.2,149.1
14b	O	ph	39.6	49.2				111.2,113.2,118.2,122.4, 126.7127.2,129.1,129.6130.4,133.5, 136.3,139.8,140.2.134.5,149.4156.8
15a	S	ph	37.9	46.2				112.2,118.4,118.9,124.1 129.7,130.7,130.4,138.8,140.8,145.4 155.4,163.5	123.8
16c	O	p-ClC6H4	37.2	48.4				110.6,112.6,118.1118.9, 125.1125.8,126.2126.6127.7129.4 129.9,134.6,139.8,141.1,158.154.8,163.7	123.8
17a	S	ph	400.4			42.3 43.		82.4,113.4118.1,119.2121.9,124.6 125.3,126.6140.5, 146.7,148.3 152.3,156.1.164.2	126.3
19b		ph		23.8		4	54.	112.6,118.8,122.3,125.6,125.1 126.3,127.7,129.1,133.8,139.7 140.3,145.5,158.9,,	125.7
20a		CH3					54.6	112.6,118.8,122.6,125.9,126.1 127.9,127.7,129,155.8, 139.7 140.3 146.7149.0,155.76
21a		CH3						113.3,118.2,119.1,125.4, 126.9,128.4,129.3.131.5,139.4,140.6 148.2,162.7	122.4
22a		p-ClC6H4						84.6,113.6,117.9,118.9, 1222.4,126.3 128.4,127.8128.9,129.6,132.8 134.4,137.6,143.4,146.8.,149.9	15.67

Table IV   Antibacterial activity of  pyrazoline and pyrazole derivatives antibacterial  activity zones of inhibition (mm)

Compound code	E. coli		Bacillus subtalis		Pseudomonas alcaligens		Salmonella sp.
	2%	4%	2%	4%	2%	4%	2%	4%
2	+++3	++3	+++5	++2	+++3	+++4	+++3	++3
3	+++4	++4	+++3	+++3	+++5	++3	+++2	++2
4	+++4	++3	+++2	++4	+++3	+++6	+++2	++3
5	+++4	++4	+++3	+++3	+++5	++3	+++2	++2
6	++++3	++3	+++5	++2	+++3	+++4	+++3	++3
7	+++4	++3	+++5	+++3	+++5	++4	+++4	++2
8	++++3	++3	+++5	++2	+++3	+++4	+++3	++3
9	+++4	++4	+++3	+++3	+++5	++3	+++2	++2
10	++++3	+++3	+++4	++3	+++3	+++4	+++3	++3
11a	+++4	++4	+++3	+++3	+++5	++3	+++2	++2
11b	++++3	++3	+++5	++2	+++3	+++4	+++3	++3
11c	+++4	++4	+++3	+++3	+++5	++3	+++2	++2
Standard drug	++++5	++4	+++5	++1	+++6	+++4	+++4	++7

ACKNOWLEDGEMENT:

The authors are thankful to SAIF, Punjab University Chandigarh for providing NMR spectra and analytical data of compounds. The authors are also thankful to Prof. U. S. Gupta, Department of Zoology, Dr. H. S. Gour Central University, Sagar (M.P.) for his kind assistance for performing insecticidal and anthelmintic activity studies in Zoology Department, Prof. M. Bhide, Department of Biotechnology, Dr. H. S. Gour University for their kind assistance for performing antimicrobial studies activity and Prof. K. S. Pitre, Head Department of Chemistry, Dr. H. S. Gour central University, Sagar (M.P.) for providing IR spectral data and necessary

Laboratory facilities.

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Received on 14.10.2012        Modified on 20.10.2012

Accepted on 25.10.2012        © AJRC All right reserved

Asian J. Research Chem. 5(10): October, 2012; Page 1293-1299