Synthesis, Characterization and In-Vitro Anti-Microbial Screening of Novel Schiff Bases of Isatin Derivatives
Ramachandran S.1* and Karanam Naga Kanika Raju2
1Department of Pharmaceutical Chemistry, S.B College of Pharmacy, Anaikuttam, Sivakasi, Tamilnadu.
2Department of Pharmaceutics, S.B College of Pharmacy, Anaikuttam, Sivakasi, Tamilnadu.
*Corresponding Author E-mail: chandruchief@gmail.com
ABSTRACT:
Novel schiff bases of isatin derivatives were synthesized. The structures of these compounds were established by means of IR, 1H-NMR analysis. All the compounds were evaluated for antimicrobial activity. Most of the compounds show significant antimicrobial activity, when compared with the standard drugs.
KEYWORDS: Isatin, Schiff bases, Antimicrobial activity.
INTRODUCTION:
Isatin is a resourceful endogenous heterocyclic molecule identified in human being and rat tissues1. Isatin, chemically known as 1H-Indole-2, 3-dione, has become a popular topic due to its various uses. Isatin was first obtained by Erdman and Laurent in 1841 as a product from the oxidation of indigo by nitric acid and chromic acids. The synthetic versatility of isatin has led to the extensive use of this compound in organic synthesis2.
The presence of several reaction centers in isatin and its derivatives makes it possible to bring these compounds into various types of reactions. Thus, keto group at position 2 and particularly, at position 3 can enter into addition at the c-o bond and into condensation with release of water. Through the NH group compounds of the isatin series are capable of entering into N-alkylation and N-acylation and into the Mannich and Michael reactions3. The synthetic versatility of isatin has stemmed from the interest in the biological and pharmacological properties of its derivatives. Schiff and Mannich bases of isatin derivatives are reported to show variety of biological activities like antibacterial, antifungal, anticonvulsant, anti-HIV, anti-depressant and anti-inflammatory activities4.
MATERIALS AND METHODS:
Antimicrobial Activity5, 6, 7:
The antimicrobial activity of the synthesized compounds was determined by cup-plate method. The organisms selected for antibacterial activity were gram positive organisms like Staphylococcus aureus (ATCC 9144), Staphylococcus epidermids (ATCC 155), gram negative organisms like Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 1688). Similarly the antifungal activity was carried out by using Aspergillus niger (ATCC 9029). The zone of inhibition measured at different concentrations of sample compounds (50, 100, 150 mcg/ml). Ciprofloxacin (100 mcg/ml) and Ketoconazole (100 mcg/ml) were used as standard drugs for antibacterial and antifungal activity respectively. Control test with solvents were performed for every assay but showed no inhibition of the microbial growth. The results are reported in Table-III.
EXPERIMENTAL:
Melting points were determined in open capillary method and are uncorrected. IR spectra were recorded on PERKIN-ELMER FT-IR spectrophotometry using potassium bromide disc method. 1H-NMR spectra were recorded on sophisticated BRUCKER 300 MHz FT- NMR using TMS (Tetramethyl Silane) as internal standard.
Method of Synthesis8--10:
Synthesis of N-benzyl isatin:
Isatin (0.42g) and benzyl chloride (0.36ml) were mixed with dimethyl formamide (10ml) in a round bottom flask. Potassium carbonate (0.96g) was added to the mixture and contents of the flask were refluxed for about two hours, cooled and poured into 50ml of cold water. The resultant precipitate is collected, washed with water, dried and recrystallized from acetonitrile.
Synthesis of imesatin:
0.01 moles of N-benzyl isatin, 0.02 moles of p-phenylene diamine and 30ml of absolute alcohol were heated under reflux on a water bath for one hour and cool the mixture to room temperature.
Filter the N-benzyl imesatin crystals through Buchner funnel.
Synthesis of the titled compounds (A1-A6):
A mixture of N-benzyl imesatin (0.01 moles) and 0.01 moles of various aromatic aldehydes were dissolved in ethanol and refluxed for two hours and kept aside. The product that has to be separated was filtered out, dried and recrystallized from ethanol.
RESULTS AND DISCUSSION:
Schiff bases of isatin derivatives were synthesized and the structures of the compounds were established by means of IR and 1H NMR analysis. All the compounds were evaluated for antibacterial and antifungal activity by cup-plate method. All the compounds have shown significant antibacterial activity and moderate antifungal activity. Physical data of the synthesized compounds are listed in Table-I. The spectral data are mentioned in Table-II.
CONCLUSION:
This study shows that isatin a molecule with a broad range of applications in synthetic, biological and clinical activity undergoes structural modification at various reactive sites. Introduction of benzyl group has increased the lipophilicity of the compound, which will enhance the absorption of the molecule. The benzyl group can also be easily hydrolyzed to give a free N-H containing compound necessary for hydrogen bonding which may be responsible for bioactivity, further benzyl groups are needed to explore the structure activity relationship. A distal aryl ring with carbimino terminal benzylidene ring is indicated for controlling the pharmacokinetic properties of the compounds. Introducing 4-chloro, bromo, increased the lipophilicity of the compounds due to its high pi-values. Based on this aspect still an evidence based research to be continued in order to get promising compounds which have ideal therapeutic index in the global market.
Table-I: Physical data of the Synthesized Compounds
|
Compound Code |
Molecular Formula |
Molecular Weight (grams) |
Melting point (oC) |
Percentage Yield |
|
A1 |
C28H22N4O3 |
462.50 |
219-223 |
81.88% |
|
A2 |
C28H22BrN3O |
496.40 |
230-235 |
85.12% |
|
A3 |
C28H22ClN3O |
451.95 |
245-249 |
88.43% |
|
A4 |
C28H23N3O2 |
433.50 |
207-209 |
86.54% |
|
A5 |
C29H25N3O2 |
447.52 |
259-263 |
94.23% |
|
A6 |
C30H27N3O3 |
477.55 |
239-243 |
95.27% |
Table II: Infra Red /1H NMR spectral study of the synthesized compounds
|
Compound |
IR (cm-1) |
1H NMR (δ, ppm) |
|
A1 |
3069.26 (CH Ar str.), 2972.99 (CH2 str.), 1727.42(C=O str.), 1677.79 (C=N str.), 1611.59 (C=C str.), 1337.11 (C-NO2 str.), 1237.49 (C-N str.). |
2.597 (s, 1H ,CH), 3.74 (s, 2H, benzyl CH2), 7.218-7.645 (m, 13H, Aromatic protons.) 7.972(m, 4H, indole), |
|
A2 |
3089.48 (CH Ar str.), 2927.85 (CH2 str.), 1686.58 (C=O str.), 1641.22 (C=N str.), 1613.45 (C=C str.), 1336.91 (C-NO2 str.), 1269.82 (C-N str.). |
2.613 (s, 1H ,CH), 3.45 (s, 2H, benzyl CH2), 7.282-7.735 (m, 13H, Aromatic protons.) 8.178(m, 4H, indole), |
|
A3 |
3089.26 (CH Ar str.), 2926.99 (CH2 str.), 1709.42 (C=O str.), 1677.79 (C=N str.), 1611.59 (C=C str.), 1237.49 (C-N str.), 754.97 (C-Cl str.). |
2.482 (s, 1H ,CH), 3.82 (s, 2H, benzyl CH2), 7.314-7.821 (m, 13H, Aromatic protons.) 8.112 (m, 4H, indole), |
|
A4 |
3620.26 (OH str.), 3069.25 (CH Ar str.), 2930.81 (CH2 str.), 1727.42 (C=O str.), 1677.79 (C=N str.), 1611.59 (C=C str.), 1337.11 (C-N str.). |
2.587 (s, 1H ,CH), 3.94 (s, 2H, benzyl CH2), 7.634-7.986 (m, 13H, Aromatic protons.) 8.112 (m, 4H, indole), |
|
A5 |
3079.48 (CH Ar str.), 2931.81 (CH2 str.), 1708.58 (C=O str.), 1645.78 (C=N str.), 1617.59 (C=C str.), 1336.91 (C-N str.), 1269.82 (COCH3 str.). |
2.445 (s, 1H ,CH), 3.76 (s, 2H, benzyl CH2), 7.047-7.784 (m, 13H, Aromatic protons.) 8.001(m, 4H, indole), |
|
A6 |
3016.36 (CH Ar str.), 2936.83 (CH2 str.), 1738.92 (C=O str.), 1654.22 (C=N str.), 1616.96 (C=C str.), 1333.41 (C-N str.), 1254.79 (COCH3 str.). |
2.482 (s, 1H ,CH), 3.48 (s, 2H, benzyl CH2), 7.012-7.644 (m, 12H, Aromatic protons.) 8.121(m, 4H, indole), |
Table III: Antibacterial and Antifungal Activity of Synthesized Compounds
|
S. No |
Compound Code |
Zone of Inhibition (mm) |
|
||||||||||||||||
|
S. aureus |
S.epidermids |
E.coli |
P.aeruginosa |
A. niger |
|||||||||||||||
|
Concentration (mcg/ml) |
|
||||||||||||||||||
|
50 |
100 |
150 |
50 |
100 |
150 |
50 |
100 |
150 |
50 |
100 |
150 |
50 |
100 |
150 |
|
||||
|
1 |
A1 |
11 |
16 |
20 |
13 |
16 |
19 |
11 |
15 |
19 |
11 |
15 |
18 |
11 |
15 |
19 |
|
||
|
2 |
A2 |
13 |
16 |
21 |
14 |
16 |
22 |
12 |
15 |
18 |
10 |
18 |
19 |
15 |
18 |
20 |
|
||
|
3 |
A3 |
15 |
18 |
23 |
11 |
17 |
21 |
15 |
18 |
21 |
12 |
17 |
21 |
15 |
18 |
23 |
|
||
|
4 |
A4 |
12 |
16 |
21 |
12 |
16 |
22 |
11 |
16 |
20 |
10 |
15 |
19 |
14 |
20 |
23 |
|
||
|
5 |
A5 |
16 |
19 |
23 |
16 |
19 |
21 |
12 |
17 |
21 |
13 |
18 |
21 |
16 |
21 |
24 |
|
||
|
6 |
A6 |
16 |
21 |
24 |
12 |
18 |
23 |
11 |
17 |
23 |
11 |
16 |
21 |
14 |
19 |
21 |
|
||
|
7 |
Solvent Control |
0mm |
0mm |
0mm |
0mm |
0mm |
|
||||||||||||
|
8 |
Standard (100 mcg/ml) |
26mm |
27mm |
25mm |
28mm |
30mm |
|
||||||||||||
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Received on 10.04.2011 Modified on 13.04.2011
Accepted on 15.04.2011 © AJRC All right reserved
Asian J. Research Chem. 4(6): June, 2011; Page 925-927