Synthesis and Biological Evaluation of Some Novel Pyrrole Derivatives

 

Saurabh Bhardwaj*, Gyanendra Kumar Sharma

Rajiv Academy for Pharmacy, Mathura, 281001.

 

ABSTRACT:

The Pyrrole is one of the significant classes of heterocyclic mixes having pharmacological and natural exercises, for example, antibacterial, antifungal, anthelmintic. The subbed pyrroles with chose functionalities at various position fill in as antecedents for the combination of different new functionalities. Pyrrole has additionally indicated wide organic exercises, for example, treatment of hyperlipidemias, mitigating, COX1/COX-2 inhibitors, 6 cytotoxic action against strong tumor model and assortment of marine and human models. A progression of new Schiff base (E)- N'- Substituted benzylidene-1H-pyrrole-2-carbohydrazide subsidiary (3a-3j) were combined by the response of 1H-pyrrole-2-carbohydrazide and fragrant aldehyde within the sight of ethanol with barely any drops of frosty acidic corrosive. The response blend was observed by TLC and recrystallized from wanted dissolvable. FTIR, 1HNMR, mass spectral and natural investigation were affirmed the structure of the blended mixes. All orchestrated mixes were screened against traditional strains for their antibacterial, antifungal and anthelmintic tasks: gram positive is B.subtilis, and S.aureus and gram negative are E. coli. Antifungal movement was screened against C. Albicans and A. niger and anthelmintic movement was screened against M. konkanensis and P. corethruses. The outcomes uncovered that 3f, 3g and 3i display increasingly strong action against the both two microorganism (gram negative and gram positive bacteria) on the opposite side compound 3a, 3g and 3h show progressively intense movement against the two growths (C. Albicans and A. niger) and compound 3c and 3d having most powerful movement with mean paralyzing time of 11.27 mins and 15.83 mins and mean death time of 19.25 mins and 24.45 mins individually when contrasted with standard medication.

 

 

INTRODUCTION:

Pyrrole is a five membered, unsaturated, mononitrogen heterocyclic compound. Pyrrole as a foundation completely present in nature and furthermore build up specifically medications, for example, a lipid bringing down specialist, as a pain relieving, as an antibacterial, as an antifungal, as an anthelmintic, as a calming and as a likely antineoplastic operator¹. In pyrrole the all ring iotas ( i.e 4 carbons +1 nitrogen) are sp2 hybridization where the sp2 cross breed orbitals cover with one another and with s orbitals of the every one of the five hydrogen particles in pyrrole framing C-C, C-N, C-H and N-H sigma (σ) bond. All these σ bond reaction in one planar.

 

This displays an expansive assortment of restorative tasks because of its well off electron setting² Pyrrole is an advantageous beginning material in numerous amalgamation on account of its high reactivity. An early blend of pyrrole, which was initially useful on the research facility scale. Hetrocyclic mixes decide to use in other engineered process. Now and again heterocyclic ring frameworks can be available to give significant non-cyclic mixes helpful in engineered work³. Pyrrole show a frail base on the grounds that the solitary pair of electrons of nitrogen iota co-work to the (4n2) π-electron cloud i.e sweet-smelling chorale. Hence the accessbility of these electron is diminished and in like manner pyrrole is a feeble base⁴

 

Pyrrole was absolutely segregated from bone oil in 1857 and its structure was first acknowledged in 1870, Although the perfect conduct of pyrrole of offer red shading to the pine wood when soaked with a corrosive prompted its revelation in 1834 as a substance found in bone oil and coal tar. Also, the pyrrole science has demonstrated the presence of pyrrole ring framework porphonilinogen (middle in biosynthesis of porphyrins and nutrient B12) biliverdin and bilirubin (pyrrole based bile shades) pyrrolonitrin ( with anti-microbial action) which gave the force to the pyrrole science⁵. The use of a basic particle with various functionalities for the combination of new heterocyclic mixes is a significant commitment in the union of novel mixes. 1 Pyrrole is one of the significant classes of heterocyclic mixes having pharmacological and natural exercises, for example, treatment of hyperlipidemias, calming, antimicrobial, anthelmintic, COX1/COX-2 inhibitors, 6 cytotoxic movement against strong tumor model and assortment of marine and human models. Subbed pyrroles were likewise found in a large portion of the basic units of normal items⁶ . Taking into account these over numerous significance of subbed pyrroles and Schiff bases, we arranged combinations of some novel Schiff bases by buildup of (E)- N'- Substituted benzylidene-1H-pyrrole-2-carbohydrazide with various sweet-smelling aldehydes, and in continuation of our endeavors to create approachs for union of new Schiff bases we report here in, a basic, proficient and high return technique for the amalgamation of novel Schiff bases (3a-3j) containing pyrrole ring⁷. Pyrrole subsidiaries are extensively group in different pharmacological exercises, for example, antibacterial , antifungal⁸, monoamine oxidase type An inhibitors movement⁹, anthelmintic¹⁰, anticonvulsant¹¹, mitigating/pain relieving movement¹², cell reinforcement action¹³, cytotoxic action¹⁴, anticancer action¹⁵.All recently incorporated mixes were tried for gram positive and gram negative microbes for antibacterial, antifungal exercises against various strains and anthelmintic activities for various worm strains¹⁶.

 

MATERIAL METHOD:

All artificial materials used in the association were of designed evaluation and were given by CDH Delhi, Qualigens Fine Labs Mumbai, S d fine chem. Ltd. Mumbai. Dissolving reason for the organized blends was done by open chamber thin procedure. Cleaning of the blends was checked by TLC by using Chloroform: Ethanol (10:1.5). Spots were seen under iodine chamber. IR spectra 1H NMR-spectra were recorded in DMSO or CDCl₃ using TMS as the inside standard. (Compound move in ppm) and mass spectra were recorded on water OPLCTQDMS in positive mode.

 

Scheme of work

 

Synthesis of 1H-pyrrole-2-carbohydrazide (2)

The 1H-pyrrole-2-carbohydrazide was set up by response of 2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethanone (1) (0.1 mol) with abundance 99 % hydrazine hydrate (15 mol). The response blend was mixed and refluxed for 6 h, at that point cooled to room temperature and poured in to super cold water. The strong item acquired was gathered by filtration, washed with water to give unadulterated compound 2 (2.89gm, 71%), m.p. 169oC, Rf 0.49.

 

E)-N'-benzylidene-1H-pyrrole-2-carbohydrazide (3)

The Schiff base were set up by response of equimolar amounts of 1H-pyrrole-2-carbohydrazide (2) (1.25gm, 0.01 mol) and benzaldehyde (1.06gm, 0.01 mol) in 40ml of ethanol alongside icy acidic corrosive (2-3 drops), was refluxes 3 hrs. The response blend was cooled. The strong acquired was sifted, washed with ethanol, dried and purged by recrystallization from DMF:water (1:1) blend to give compound 3 (1.86gm, 69%), m.p. 188oC Rf 0.71.

(E)-N'-(3-chlorobenzylidene)-1H-pyrrole-2-carbohydrazide (3a)

Yield 44%, m.p. 185^oC, R_f 0.47; FTIR (KBr) ν_maxcm^-1: 3053.37 (aromatic C-H stretching), 1639.42 (aromatic C=C stretching), 1529.26 (C=N stretching), 1671.34 (C=O stretching), 1031.51 (aromatic C-C stretching), 3456.41 (N-H stretching), 1316.71 (C-N stretching), 712.16 (aromatic C-Cl stretching); ¹H NMR (DMSO-d₆): δ 6.790 (s, 1H, aromatic H), 7.418-7.731 (m, 3H, aromatic H), 8.012-8.481 (m, 3H, aromatic H), 8.642 (s, 1H, N=CH), 10.953 (s, 1H, pyrrole NH), 11.324 (s,1H, NH-N); Anal Calcd. for C₁₂H₁₀ClN₃O: C, 58.19; H, 4.07; N, 16.97; O, 6.4 Found: C, 58.21; H, 4.09; N, 16.98; O,6.48%

 

(E)-N'-(3,5-dichlorobenzylidene)-1H-pyrrole-2-carbohydrazide (3b):

Yield 45%, m.p. 210 ^oC, R_f 0.63; FTIR (KBr) ν_maxcm^-1 : 3068.15 (aromatic C-H stretching), 1642.26 (aromatic C=C stretching), 1541.12 (C=N stretching), 1702.21 (C=O stretching), 1030.21 (aromatic C-C stretching), 3472.67 (N-H stretching), 1221.16 (C-N stretching), 778.12 (aromatic C-Cl stretching); ¹H NMR (DMSO-d₆): δ 6.691-7.012 (m, 3H, aromatic H), 7.121 (s, 1H, aromatic H), 7.353 (s, 1H, aromatic H), 7.621 (s, 1H, aromatic H), 8.742 (s,1H, N=CH), 10.842 (s, 1H, pyrrole NH), 11.121 (s,1H, NH-N); Anal . for C₁₂H₉Cl₂N₃O: C, 51.09; H, 3.22; N, 14.89; O, 5.67 Found: C, 51.07; H, 3.24; N, 14.87; O, 5.69%

 

(E)-N'-(4-nitrobenzylidene)-1H-pyrrole-2-carbohydrazide (3c)

Yield 51%, m.p. 138^oC, R_f 0.58; FTIR (KBr) ν_maxcm^-1: 3042.31 (aromatic C-H stretching), 1636.32 (aromatic C=C stretching), 1554.26 (C=N stretching), 1679.31 (C=O stretching), 1234.52 (aromatic C-C stretching), 3483.17 (N-H stretching), 1050.29 (C-N stretching), 1351.12 (aromatic N=O stretching); ¹H NMR (DMSO-d₆): ): δ 6.701-6.732 (dd, J= 9.29, 4H, aromatic H), 7.021-7.422 (m, 3H, aromatic H), 7.782 (s, 1H, pyrrole NH), 8.642 (s,1H, N=CH), 8.831 (s,1H, NH-N); Anal Calcd for C₁₂H₁₀N₄O₃: C, 55.81; H, 3.90; N, 21.70; O, 18.59 Found: C, 55.83; H, 3.88; N, 21.72; O, 18.57%

 

(E)-N'-(2-nitrobenzylidene)-1H-pyrrole-2-carbohydrazide (3d):

Yield 54%, m.p.152 ^oC, R_f 0.68; FTIR (KBr) ν_maxcm^-1: 3073.19 (aromatic C-H stretching), 1639.31 (aromatic C=C stretching), 1563.29 (C=N stretching), 1733.27 (C=O stretching), 1154.32 (aromatic C-C stretching), 3431.81 (N-H stretching), 1248.12 (C-N stretching), 1379.56 (aromatic N=O stretching); ¹H NMR (DMSO-d₆): δ 6.424-7.026 (m, 3H, aromatic H), 7.523-8.428 (m, 4H, aromatic H), 8.568 (s,1H, N=CH), 10.761 (s, 1H, pyrrole NH), 10.982 (s,1H, NH-N); Anal Calcd. for C₁₂H₁₀N₄O₃: C, 55.81; H, 3.90; N, 21.70; O, 18.59 Found: C, 55.79; H, 3.92; N, 21.68; O, 18.58%

 

(E)-N'-(3-hydroxybenzylidene)-1H-pyrrole-2-carbohydrazide (3e)

Yield 81%, m.p. 220^oC, R_f 0.73; FTIR (KBr) ν_maxcm^-1: 3083.24 (aromatic C-H stretching), 1621 (aromatic C=C stretching), 1523.26 (C=N stretching), 1737.15 (C=O stretching), 1229.31 (aromatic C-C stretching), 3481 (N-H stretching), 1071.17 (C-N stretching), 3279.13 (aromatic O-H stretching); ¹H NMR (DMSO-d₆): δ 6.418-7.121 (m, 3H, aromatic H), 7.264 (s, 1H, aromatic H), 7.346-7.709 (m, 3H, aromatic H), 8.012 (s,1H, N=CH), 9.921(s,1H, aromatic OH) 10.786 (s, 1H, pyrrole NH), 10.856 (s,1H, NH-N); Anal . for C₁₂H₁₁N₃O₂: C, 62.87; H, 4.84; N, 18.33; O, 13.96 Found: C, 62.89; H, 4.82; N, 18.35; O, 13.98%

 

(E)-N'-(4-hydroxybenzylidene)-1H-pyrrole-2-carbohydrazide (3f):

Yield 72%, m.p. 193^oC, R_f 0.83; FTIR (KBr) ν_maxcm^-1: 3080.23 (aromatic C-H stretching), 1623.46 (aromatic C=C stretching), 1612.10 (C=N stretching), 1643 (C=O stretching), 1301.46 (aromatic C-C stretching), 3452.15 (N-H stretching), 1160.17 (C-N stretching), 3291.42 (aromatic O-H stretching); ¹H NMR (DMSO-d₆): δ 6.721-6.840 (d, 2H, aromatic H), 6.982-7.402 (m, 3H, aromatic H), 7.521-7.592 (d, 2H, aromatic H), 8.109 (s,1H, N=CH), 9.861(s,1H, aromatic OH) 10.752 (s, 1H, pyrrole NH), 10.956 (s,1H, NH-N); Anal.for C₁₂H₁₁N₃O₂: C, 62.87; H, 4.84; N, 18.33; O, 13.96 Found: C, 62.85; H, 4.86; N, 18.31; O, 13.95%

 

(E)-N'-(4-methoxybenzylidene)-1H-pyrrole-2-carbohydrazide (3g)

Yield 56%, m.p. 147^oC, R_f 0.57; FTIR (KBr) ν_maxcm^-1: 3091.12 (aromatic C-H stretching), 1603.42 (aromatic C=C stretching), 1605.47 (C=N stretching), 1776.15 (C=O stretching), 1311.39 (aromatic C-C stretching), 3475.23 (N-H stretching), 1067.24 (C-N stretching), 1258.13 ( C-O-C stretching), 2931.13 (aliphatic C-H stretching); ¹H NMR (DMSO-d₆): δ 3.791 (s, 3H, OCH₃ ), 6.981-7.002 (d, 2H, aromatic H), 7.126-7.542 (m, 3H, aromatic H), 7.621-7.654 (d, 2H, aromatic H), 8.521 (s,1H, N=CH), 10.843 (s, 1H, pyrrole NH), 11.213 (s,1H, NH-N); Anal. Calcd. for C₁₃H₁₃N₃O₂: C, 64.19; H, 5.39; N, 17.27; O, 13.15 Found: C, 64.17; H, 5.37; N, 17.29; O, 13.17%

 

(E)-N'-(3,4-dimethoxybenzylidene)-1H-pyrrole-2-carbohydrazide (3h)

Yield 44%, m.p. 150^oC, R_f 0.78; FTIR (KBr) ν_maxcm^-1: 3048 (aromatic C-H stretching), 1608.11 (aromatic C=C stretching), 1598.27 (C=N stretching), 1613.18 (C=O stretching), 1417.12 (aromatic C-C stretching), 3463.41 (N-H stretching), 1168.13 (C-N stretching), 1262 ( C-O-C stretching), 2968.46 (aliphatic C-H stretching); ¹H NMR (DMSO-d₆): δ 3.801-3.836 (d, 6H, (OCH₃)₂ ), 7.023-7.052 (d, 1H, aromatic H) 7.161-7.210 (d, 1H,aromatic H),7.342 (s, 1H, aromatic H) 7.621-8.001 (m, 3H, aromatic H), 8.146 (s,1H, N=CH), 10.889 (s, 1H, pyrrole NH), 11.012 (s,1H, NH-N); Anal. for C₁₄H₁₅N₃O₃: C, 61.53; H, 5.53; N, 15.38; O, 17.56 Found: C, 64.55; H, 5.51; N, 15.36; O, 17.54%

 

(E)-N'-(4-chlorobenzylidene)-1H-pyrrole-2-carbohydrazide (3i)

Yield 54%, m.p. 188^oC, R_f 0.59; FTIR (KBr) ν_maxcm^-1 : 3079.18 (aromatic C-H stretching), 1602.32 (aromatic C=C stretching), 1582.14 (C=N stretching), 1623.17 (C=O stretching), 1365.12 (aromatic C-C stretching), 3477.67 (N-H stretching), 1288.82 (C-N stretching), 727.43 (aromatic C-Cl stretching); ¹H NMR (DMSO-d₆): δ 6.421-7.161 (m, 3H, aromatic H), 7.216-7.318 (d, 2H, aromatic H), 7.821-7.901 (d, 2H, aromatic H), 8.264 (s, 1H, N=CH), 10.764 (s, 1H, pyrrole NH), 11.181 (s,1H, NH-N); Anal. Calcd for C₁₂H₁₀ClN₃O: C, 58.19; H, 4.07; N, 16.97; O, 6.46 Found: C, 58.17; H, 4.09; N, 16.99; O, 6.48%

 

(E)-N'-(2,4-dimethylbenzylidene)-1H-pyrrole-2-carbohydrazide (3j)

Yield 64%, m.p. 134^oC, R_f 0.48; FTIR (KBr) ν_maxcm^-1: 3097.12 (aromatic C-H stretching), 1612.13 (aromatic C=C stretching), 1568.61 (C=N stretching), 1680.91 (C=O stretching), 1449.57 (aromatic C-C stretching), 3481.39 (N-H stretching), 1233 (C-N stretching), 2878.43 (aliphatic C-H stretching); ¹H NMR (DMSO-d₆): δ 2.461 (s, 3H, (CH₃), 2.642 (s, 3H, (CH₃), 6.521-7.104 (m, 3H, aromatic H), 7.218(s, 1H, aromatic H), 7.356-7.417 (d, 1H, aromatic H), 7.621-7.701 (d, 1H, aromatic H), 8.124 (s,1H, N=CH), 10.664 (s, 1H, pyrrole NH), 11.016 (s,1H, NH-N); Anal. Calcd. for C₁₄H₁₅N₃O: C, 69.69; H, 6.27; N, 17.41; O, 6.63 Found: C, 69.67; H, 6.29; N, 17.43; O, 6.65%

 

Antibacterial activity

The antibacterial movement of recently incorporated mixes had been tried by methods for circle dissemination strategy on supplement agar medium towards following bacterial strains: S. aureus, and B. subtilis (gram positive) and E. coli and and P. aeruginosa (gram negative).

 

In the circle dissemination approach, paper plate impregnated with mixes broke up in DMSO at fixation 25, 50 and 100 had been utilized. Plate impregnated with DMSO had been utilized as dissolvable control for antibacterial action because of free solvency of investigate mixes. The microorganism custom changed into spread over supplement agar media in petri-dishes, and afterward the plate impregnated with the appropriate response transformed into set on the outside of the media immunized with the bacterial pressure. The plates had been brooded at 35°C for 24 hrs for bacterial societies. After hatching, the territory of hindrance around the plate become found. The zone of restraint demonstrates that the mixes hinder blast of microorganism. Each looking at is executed in triplicate. Ciprofloxacin at conc. 100 were utilized as standard medication for antibacterial action. A progression of compound 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h , 3i and 3j have been inspected for the side interest noted. Results have been deciphered in expressions of distance across (mm) of zone of hindrance.

 

Table 1: Antibacterial activities of synthesized compounds

Code of compound	Diameter of zone of inhibition (mm)[ mean ±S.D. (n=3)]
	B.subtilis			E. coli			S. aureus
	25 µg ml-1	50 µg ml-1	100 µg ml-1	25 µg ml-1	50 µg ml-1	100 µg ml-1	25 µg ml-1	50 µg ml-1	100 µg ml-1
3a	3.23±0.30	5.29±0.50	10.01±0.40	3.25±0.29	4.10±0.40	9.08±0.41	4.20±0.41	6.58±0.50	10.28±0.22
3b	6.41±0.51	9.41±0.43	13.96±0.50	3.80±0.41	8.36±0.60	11.18±0.42	4.42±0.60	7.16±0.29	10.46±0.70
3c	4.49±0.42	8.23±0.52	11.21±0.48	3.09±0.80	6.52±0.73	9.22±0.41	3.76±0.20	5.06±0.86	9.29±0.70
3d	3.43±0.25	6.26±0.30	9.66±0.50	4.10±0.32	7.91±1.10	11.13±0.41	3.10±0.20	5.83±0.30	8.60±0.80
3e	4.62±0.42	8.52±0.41	11.31±0.39	3.43±0.60	7.16±1.00	9.84±0.40	3.07±0.39	5.50±0.40	8.35±0.80
3f	6.72±0.41	9.66±0.39	14.22±0.42	4.39±0.45	8.75±0.45	14.22±0.50	5.78±0.60	8.92±0.78	13.66±1.00
3g	5.80±0.25	10.42±0.30	16.16±0.51	4.55±0.80	8.66±0.82	15.78±0.62	5.17±0.41	8.84±0.65	13.84±0.40
3h	4.88±0.30	7.52±0.39	11.62±0.40	4.63±0.40	10.16±0.42	13.30±0.40	3.45±0.50	5.31±0.32	9.44±0.50
3i	4.83±0.20	9.88±0.31	11.48±0.40	5.05±0.50	9.22±0.78	14.14±0.70	6.28±0.54	9.45±0.60	14.12±0.40
3j	6.65±0.25	9.31±0.21	14.85±0.40	4.15±0.20	7.82±0.25	10.29±0.39	4.25±0.20	7.38±0.40	10.40±0.21
Ciprofloxacin	-	-	18.28±0.30	-	-	19.22±0.40	-	-	19.60±0.70

 

Table 2: Antifungal activities of synthesized compounds

Code of compound	Diameter of zone of inhibition in mm (mean± S.D.. (n=3)]
	C.albicans			A.niger
	25 µg ml-1	50 µg ml-1	100 µg ml-1	25 µg ml-1	50 µg ml-1	100 µg ml-1
3a	5.11±0.42	10.16±0.40	10.26±0.40	5.26±0.39	10.26±0.40	11.26±0.41
3b	4.26±0.39	8.96±0.32	11.26±0.30	4.98±0.21	11.16±0.20	11.36±0.20
3c	6.11±0.19	10.23±0.20	16.26±0.41	3.36±0.33	8.12±0.30	14.26±0.31
3d	4.31±0.31	7.87±0.30	11.26±0.32	3.41±0.42	7.89±0.41	16.26±0.42
3e	3.06±0.45	9.16±0.42	14.26±0.45	3.95±0.19	9.16±0.20	21.26±0.22
3f	4.54±0.40	9.09±0.39	12.26±0.39	3.86±0.40	9.20±0.40	12.26±0.41
3g	5.86±0.32	10.24±0.42	14.26±0.40	5.44±0.36	10.95±0.39	10.26±0.40
3h	6.35±0.21	10.26±0.25	17.26±0.22	6.56±0.40	11.06±0.45	18.26±0.44
3i	6.20±0.30	11.48±0.31	19.26±0.41	3.44±0.42	8.26±0.40	13.26±0.41
3j	4.16±0.40	9.28±0.41	16.26±0.42	3.26±0.25	8.29±0.21	14.26±0.20
Fluconazole		16.88±0.40			16.63±0.30

 

Antifungal activity:

The in vitro antifungal screening of recently blended mixes was finished by utilizing paper plate dispersion technique on supplement agar media. A fifteen days old culture of Aspergillus niger and Candida albicans was utilized as test life form. A spore suspension in ordinary saline was set up from the way of life of the test organisms on sabouraud's stock media. Each petri plate was separated into 5equal parts along the distance across to put one circle in each segment. Three plates of test were set on three bits along with one circle for reference tranquilize Fluconazole [2-(2,4-difluorophenyl)-1,3-di(1H-1,2,4-triazol-1-yl)propan-2-ol] and the last one inseminated with the dissolvable (DMF) as negative control. Test tests were tried at 50, 100 and 200µg ml-1 focus in DMF. Fluconazole in the grouping of 50µg ml-1 was utilized as a standard medication for antifungal action. The petri plates immunized with parasitic societies were brooded at 25^oC for 48 hrs. Antifungal action was controlled by estimating the width of the restraint zone for triplicate sets. The measurements acquired for the test were contrasted and that delivered by the standard medication Fluconazole. A progression of compound 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h , 3i and 3j have been analyzed for the side interest noted. Results have been deciphered in expressions of breadth (mm) of zone of hindrance.

 

Anthelmintic activity:

The newly synthesized derivatives showed promising anthelmintic activity against M.konkanensis and P.corenthruses species of earthworms. Suspensions of samples were prepared by triturating 100 mg of synthesized compounds with 10 ml of Tween 80 (0.5%) and 10 ml of distilled water and the resulting mixtures were stirred using a mechanical stirrer for 30 min. The suspension was diluted to contain0.2% w/v of the test samples. Suspension of reference drug, mebendazole was prepared in a similar way by triturating drug with tween 80 (0.5%) and distilled water separately and finally diluted to contain 0.2% w/v of mebendazole (Garg and Atal method). Five earthworms of almost similar sizes (2 inch in length) were placed in petri plates of 4 inch diameter containing 50 ml of suspension of test sample and reference drug at room temperature. Another set of five earthworms were kept as control in 50 ml suspension of distilled water and Tween 80 (0.5%). 50 ml each of the suspensions of the test compounds were added into separate petri plates containing five earthworms in each. The time required for the paralysis and death of the worms was noted. The death time was ascertained by placing the earthworms in warm water at 50^oC. Mebendazole at concentration  ml-1 become used as standard drug for anthelmentic pastime. ^{A series of compound 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i and 3j were examined for the pastime stated.} Results were interpreted in terms of mean paralyzing time and mean death time are shown in table.

 

Table 3: Data of anthelmintic activity

Compound No.	Earthworm species
	M.konkanensis		P.corenthruses
	Mean paralyzing time (min)	Mean death time (min)	Mean paralyzing time (min)	Mean death time (min)
3a	20.72±0.52	30.53±0.60	29.21±0.40	39.98±0.42
3b	19.63±0.42	27.13±0.40	27.53±1.45	37.47±1.21
3c	11.27±0.83	19.25±0.50	15.83±0.39	24.45±0.52
3d	12.44±1.92	23.83±0.50	18.73±2.22	29.13±1.52
3e	30.56±1.41	66.43±0.20	32.83±1.16	71.71±0.40
3f	34.21±0.32	52.36±0.91	31.47±1.19	44.13±0.40
3g	15.34±0.37	24.65±0.70	20.52±1.21	31.86±1.34
3h	18.46±0.60	24.21±0.32	23.65±0.63	34.75±0.50
3i	19.26±0.82	29.36±0.41	26.94±0.21	37.91±0.71
3j	25.32±0.58	33.26±0.94	46.16±0.85	71.41±0.92
Control	-	-	-	-
Mebendazole	12.27±0.58	20.19±0.70	17.49±1.20	28.71±1.10

 

RESULT AND DISCUSSION:

The synthesized pyrrole derivatives (E)-N'-benzylidene-1H-pyrrole-2-carbohydrazide were synthesized in moderate to excellent yields by Trichloroacetylation of 1H-pyrrole by using equivalent amount of 1H-pyrrole and trichloroacetyl chloride were added to a stirring solution of K₂CO₃ (catalytic amount). The 1H-pyrrole-2-carbohydrazide was prepared by reaction of 2,2,2-trichloro-1-(1H-pyrrol-2-yl)ethanone with excess 99 % hydrazine hydrate. The substituted (E)-N'-benzylidene-1H-pyrrole-2-carbohydrazide The Schiff base were prepared by reaction of equimolar quantities of 1H-pyrrole-2-carbohydrazide and substituted benzaldehyde and results in the formulation of final derivative of pyrrole (3a-3j).

 

^The structure of newly synthesized pyrrole derivatives have been completed through IR spectroscopy, ¹H NMR and mass spectroscopy, The FTIR spectra of newly synthesized derivatives showed the presence of characteristic absorption band in the region 3100-3000 cm^-1 for aromatic C-H str., 1620-1520 cm^-1 for C=N stretching, 1350-1050 cm^-1 for C-N stretching, 1650-1600 cm^-1 for C=C stretching. ¹H NMR spectra of synthesized derivatives displayed the characteristic peaks in the region 6.673-8.035ppm for aromatic protons, 3.801-3.836ppm –(OCH₃)₂ protons, 3.791ppm –OCH₃ protons, 9.861-9.921ppm for –OH protons. All the newly synthesized derivatives were evaluated for antibacterial, antifungal and anthelmintic activities respectively.

 

The results confirmed that newly synthesized compounds 3b, 3f, 3g and 3j possess maximum potency against B.subtilis due to presence of electron withdrawing group –Cl and electron donating groups –(OCH₃) _, -OH and (CH₃)₂. Compounds 3c, 3e, 3h, 3i showed moderate antibacterial activity against B.subtilis . Compounds 3f, 3g and 3i exhibited maximum activity against S.aureus due to presence of electron donating groups –OH and -OCH₃ and electron withdrawing group –Cl. Compounds 3f, 3g, 3h and 3i contains maximum potency against E.coli due to presence of electron donating groups -(OCH₃) & -OH and electron withdrawing group –Cl. Compounds 3a, 3d and 3j were found to be moderate potency against E.coli. Compounds 3a, 3g, 3h and 3i displayed maximum potency against C.ablicans due to presence of electron withdrawing groups –Cl and electron donating group -OCH₃ While 3b, 3e and 3f showed moderate activity against C.ablicans. On the other side, derivatives 3a, 3b, 3g and 3h possess good activity against A. niger due to presence of electron withdrawing group –Cl and electron donating groups -OCH_3. The result of anthelmintic data was carried out against M.konkanensis and P.corenthruses species of earthworms confirmed that derivatives 3a, 3b, 3c, 3d, 3g, 3h, 3i were shown moderate to good anthelmintic activity as compared to standard drug mebendazole at conc. 2 mg Ml^-1. On screening it was found that 3c and 3d having most potent activity with mean paralyzing time of 11.27 mins & 15.83 mins and mean death time of 19.25 mins & 24.45 mins respectively as compared to standard drug with mean paralyzing time of 12.27 mins and mean death time 20.19 mins. Persual of anthelmintic activity was confirmed that compound having nitro substitution at C-2 and C-4 of benzaldehyde ring show promising anthelmintic activity. Because of the presence of nitro group which enhance the stabilityof ring responsible for high log P value that further enhances activity of compound.

 

CONCLUSION:

A progression of novel pyrrole subordinates were described by FTIR, 1HNMR, mass fragmentation and basic examination. All blended mixes have great to direct action against bacterial, contagious strains and various types of night crawler.

 

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Accepted on 26.02.2021           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(11):5749-5754.