Design, Synthesis and Biological Activities of Isatin Derivatives

Transcription

1 3P P position P we hemical Science Transactions DI:0.7598/cst , 4(), 08- RESEAR ARTILE Design, Synthesis and Biological Activities of Isatin Derivatives REEA D SUZA and AMIT ATTREE Department of hemistry, Sam igginbottom Institute of Agriculture, Technology & Sciences (Deemed-to-be-University), Allahabad -007, (U.P.), India srreenabs@gmail.com Received 8 August 04 / Accepted 5 September 04 Abstract: Two compounds ISD- and ISD- were synthesized by -Alkylation method. 3 Synthesized compounds were characterized by IR, UV, Mass and P P MR and P P MR. The biological activities of both the compounds were evaluated. ISD- shows good antibacterial and antifungal activity as well as very little antioxidant property where as ISD- shows activity only towards negative strains of bacteria. Keywords: Isatin, ISD-, ISD-, -Alkylation Introduction Isatin is one of the few compounds to have been synthesized before it was discovered in nature. Isatin (--indole-,3-dione) and its derivatives possess a broad range of biological and pharmacological properties and are widely used as starting materials for the synthesis of a broad range of heterocyclic compounds and as substrates for drug synthesis. From literaturep come to know that Isatin containing synthetic compounds and their derivatives are known to be associated with broad spectrum of biological activity. In humans and other mammals, isatin is found as an endogenous molecule. Although the Metabolic pathways of isatin have not yet been fully elucidated; it has been proposed that it is synthesised in vivo from tryptophan-rich foods such as meat, dairy and whole grainsp P. Formerly, the study of Isatin derivatives was connected with dye synthesis, but more recently these heterocycles have been shown to demonstrate antiprotozoal, antibacterial, antifungalp P, antiviralp P. Anti- 7 8 IV, anticonvulsantp P, antitumoralp P, anti-inflammatory and antihelminthic activities; influence neurodegenerative diseases; participate in metabolism; acetylcholinesterase inhibitors and 9 stimulate the growth of plantsp P. Drugs containing the Isatin skeleton are used to treat 0 st diseases such as epilepsyp P, tuberculosisp bulimiap P. The various substituents at P rd of the Isatin, are phenyl ring moieties, heterocyclic rings and aliphatic system. Isatin is one of the most promising new classes of heterocyclic molecules having many interesting activity profiles and well-tolerated in humanp P. Since Isatins have active area for medicinal chemistry there is a great need to create novel Isatin derivatives for emerging drug targets.

2 P for hem Sci Trans., 05, 4(), Experimental Isatin derivatives ISD- and ISD- were prepared according to the literature by -alkylation 3 methodp P. Synthesized derivatives were characterized by spectrometry method. UV-Vis spectra were recorded on a Shimadzu UV-450 spectrophotometer controlled by the Win Lab Software through computer. IR spectra was recorded by Perkin-Elmer Spectrum RX- - FT-IR spectrometer in the range cmp P. Mass spectra by uker Micro TF III, 3 Analyzed in positive Mode, Source voltage: 4500 V and P P MR and P P MR were recorded by uker 400 Mz MR spectrometer controlled by TPSPI software working 8 at 400 Mz at 0 º. By disc diffusion method anti bacterialp antifungal activity was 4 5 evaluatedp P. Antioxident activity was evaluated by DPP methodp P. + Acetone aet isatin Scheme. Synthesis of ISD- Isatin (.94, 0 mmol) and,-dibromo ethane (0.865 g, 0 m.mol) was dissolved in 00 ml of acetone taken in a 50 ml round bottom flask. Then few drops of base (aet) was added till 3 it becomes dark green color and refluxedp hours at 50 º. Then the reaction mixture was kept for evaporation. The yellow crystals formed were filtered and air dried. Yield 5% mp 66 º -((Z)--oxo-3-(-oxoindolin-3-ylidene) indolin--yl) ethyl) indoline-,3-dione. (ISD-) - IR (K cmp P): (aromatic -), 30.6(-), 888.3(-RR-RR-), 709 (=), 60 (=), 333 ( aromatic). UV (ethanol nm): 54 (π π for conjugated = group), 9(π π for unconjugated = group). MS (m/z) P PMR (400Mz DMS /ppm): 3 3.(4 in -RR-RR-), 6.5 to 8.4 ( in Ar) and 0. ( of -). P P MR (400Mz DMS /ppm): 3(RR-RR), 0-4(Aromatic ), 80(-) and 05 (-). 3 + aet Acetone + 3 Scheme. Synthesis of ISD-

3 P for 0 hem Sci Trans., 05, 4(), 08- Isatin (4.4 g, 30 mmol) and,3,5-tris(bromomethyl)benzene (3.56 g, 0 m.mol) was dissolved in 00 ml of acetone taken in a 50 ml round bottom flask. Then few drops of 3 base (aet) was added till it becomes dark green color and refluxedp hours at 50 º. Then the reaction mixture was kept for evaporation. The orange red solid formed were filtered and air dried. Yield 6% mp 6 º.,3,5-Tris(indole,3 dione methyl)benzene.(isd-) - IR (K cmp P): (aromatic -), 30.6(-), 888.3(-RR-), 709 (=), 334( aromatic). UV (ethanol nm): 44 (π π for conjugated = group), 94(π π for unconjugated = group). MS (m/z) P PMR (400Mz DMS /ppm): 3.(6 in 3 -RR-), ( in Ar of isatin) and 6.7 (3 of central aromatic ring). P PMR (400Mz DMS /ppm): 40(3 of-rr-), 09-30(Aromatic of Isatin), 40( of mesytilene) and 80 (-). Results and Discussion - The characteristic frequency cmp Pcorresponds to aliphatic stretch and frequency cmp Pcorresponding to -RR- bending in alkanes shows that -alkylation has taken place for the formation of ISD-. Absorption maxima in the UV region 54 nm and 9 nm are assignable to π π transition for conjugated and unconjugated = group respectively. EI mass spectrum was recorded gives peak at m/z at 43.9 is due to parent ion with the molecular mass 435 and the proton MR of spectrum ISD- shows signal at 3. ppm assignable to proton attached with alkanes. The resonance at ppm is assigned to the 3 aromatics protons in all three rings. The P P MR spectrum of ISD- shows a signal at 3 ppm for aliphatic carbon, the resonance at 0-40 ppm is assigned to aromatic carbons, 80 ppm shows carbonyl groups attached with group. 05 ppm shows carbonyl carbon attached to amide group. - The characteristic frequency 474 cmp Pcorresponds to alkane vibration and absence of vibration shows that -alkylation has taken place in ISD-. ISD- shows two characteristic absorption maxima in the UV region 44 nm and 94 nm are assignable to π π transition for conjugated and unconjugated = group respectively. EI mass spectrum was recorded gives peak at m/z at which agrees with the molecular mass of the designed compound. The proton MR of spectrum shows signal at 3. ppm assignable to proton attached with alkanes. The resonance at ppm is assigned to the aromatics protons in all four 3 rings. The P P MR spectrum of ISD- shows a signal at range ppm for aliphatic carbon, the resonance at ppm is assigned to aromatic carbons of Isatin, resonance at 40 ppm carbons of mesitylene, 80 ppm shows carbonyl groups attached with group. 05 ppm shows carbonyl carbon attached to amide group. Antimicrobial activity Enterobacter aerogenes and Yersinia enterocolitica ISD- has shown the activity towards Gram egative bacteria. ISD- shows good activity towards the Gram positive bacteria, Staphylococcus aureus, Micrococcus luteus, Gram negative bacteria Enterobacter aerogenes Yersinia enterocolitica, fungal strains Aspergillus flavus and Trichophyton rubrum (Table ). ISD- shows only 9.5% of free radical scavenging property (Figure ).

4 hem Sci Trans., 05, 4(), 08- Table. Antibacterial and antifungal activities of ISD- and ISD- S.o Pathogen Zone inhibition, mm (mg/disc) ontrol ISD- ISD- ISD-ISD- ISD- ISD- ISD- ISD- Staphylococcus aureus (96) Micrococcus luteus (06) Enterobacter aerogenes () Yersinia enterocolitica (840) Aspergillus flavus (AF) Scopulariopsis sp (0) % inhibition Figure. Free radical scavenging of ISD- derivative onclusion Thus from the study it can be concluded that among the two synthesized compounds ISD- shows more activity as compared to ISD- which may be due to presence of the aromatic ring in the structure of the isatin derivative,3,5-tris(indole,3 dione methyl)benzene. Further studies can be conducted in derivatising these compounds by substituting and 3 positions, along with substitution on the aromatic ring. By this process the activities of the compounds can be enhanced. Thus these compounds provide the opportunities to design new derivatives with improved activities and applications. These compounds can be applied in medicinal chemistry as they show various biological activities. Acknowledgement I am grateful to the department of hemistry, Loyola ollege, hennai, for providing lab facilities and Dr John Maria Xavier (Asst. prof. Loyola ollege hennai) for his guidance and Kala, research scholar for the help given during my project work. References. Vinit Raj, Int J urrent Pharma Res., 0, 4(4), -9.. Vine K L, Matesic L, Locke J M and Skropeta D, Recent highlights in the development of isatin-based anticancer agents. In M. Prudhomme (Eds.), Advances in Anticancer Agents in Medicinal hemistry Sharjah, UAE: Bentham, Science Publishers, 03, Varma R S and obles W L, J Med hem., 967, 0(3), 50-53; 3TDI:0.0/jm0035a0603T oncentration in µg/ml

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