INTRODUCTION:

Heterocyclic chemistry deals with heterocyclic compounds wich are widely distributed in nature and are essential to life.the majority of known molecules are heterocyclic and heterocycles dominate the fields of biochemistry, medicinal chemistry, dyestuffs and photographic¹. The isatin is a class of heterocyclic compounds. Isatin has also been found to be plants, animals and fungi^2-4. It is a one of the component of coal tar^5. It prepared from cyclizing the condensation product of chloral hydrate, aniline and hydroxylamine in sulfuric acid. This reaction is called the Sandmeyer isonitrosoacetanilide isatin synthesis⁶. Isatin exists in two forms, lactam form and lactimform. Both are derivatives of 2, 3-dihydroindole. This is an example for amido-imidol tautomeric system⁷.

It may be prepared from cyclizing the condensation product of chloral hydrate, aniline and hydroxylamine in sulfuric acid. This reaction is called the sandmeyer isonitrosoacetanilide isatin synthesis⁸. Isatin have been identified as interesting compounds that are collaborate with various biological activities⁹. The purpose of this review is to provide information on the pharmacological activities of isatin and its derivative.

Biological activities of isatin derivatives:

1. Antiviral activity¹⁰:

Pena LJ et al has been reported the Isatin Derivatives and Their Antiviral Properties against Arboviruses. Arboviruses have been spreading rapidly throughout the Western Hemisphere in recent decades. Among the Arboviruses with high morbidity and mortality are the members of the Alpha virus and Flavivirus genera. Within the first genus, Chikungunya Virus (CHIKV) is considered one of the most challenging human arboviral infections worldwide, against which there are no specific antiviral. Flaviviruses are some of the main viruses responsible for encephalitis, hemorrhagic disease and developmental defects. Dengue virus (DENV), Japanese Encephalitis Virus (JEV), West Nile Virus (WNV) and Zika Virus (ZIKV) are examples of flaviviruses without clinically approved antiviral agents. Thus, the search for new antiviral becomes highly important. One of the strategies that can be employed to obtain new drugs is the identification and utilization of privileged structures. Isatin is an example of a privileged molecular framework, displaying a broad spectrum of biological activities, including antiviral action. Obtaining and studying the antiviral properties of isatin derivatives have helped to identify important agents with potential activity against different arboviruses. This article reviews some of these isatin derivatives, their structures and antiviral properties reported against this important group of viruses.

2. Anticonvulsant activity¹¹:

Garima M et al has been reported the Recent Advancement in Synthesis of Isatin as Anticonvulsant Agents. Isatin (1H-indole-2,3-dione) and its analog, are versatile substrates which acts as a precursor for large number of pharmacologically active compounds, thus having a significant importance in the synthesis of different heterocycliccompound.Isatin shows varity of biological activities such as antimicrobial, anticancer, antiviral, anticonvulsant, anti-inflammatory and analgesic. This review focused on isatin synthetic methods and its biological activity as anticonvulsant. An Isatin derivative shows potent anticonvulsant activity at low concentration among all the derivatives, Schiff bases are found to be most potent anticonvulsant agent.

3. Anti-tubercular activity^12,13:

Usha Rani U et al has been reported the Synthesis and Biological Evaluation of Isatin incorporated Quinoxalines as Anti-Tubercular Agents. Heterocyclic compounds are very much used as therapeutic agents. Indole, an important class of nitrogen, containing heterocyclic with wide variety of biological activities. Isatin is a derivative of indole which is indole-2, 3 dione. Isatin is reported for ant tubercular activity. Quinoxalines is also reported for various biological activities. So, a scheme was designed and isatin incorporated Quinoxalines were prepared to improve biological activity. In the present research isatin incorporated Quinoxalines (1, 1A, 1B and 1C) were prepared, and were characterized by using TLC, IR, NMR and MASS spectral data. They were evaluated for anti-tubercular activity. Among those derivatives, compound 1 showed good activity.

4. Anticancer activity¹⁴:

Abdel-Aziz H A et al has been reported the Isatin-benzoazine molecular hybrids as potential anti proliferative agents: synthesis and in vitro pharmacological profiling. In continuation of our endeavor with respect to the development of potent and effective isatin-based anticancer agents, we adopted the molecular hybridization approach to design and synthesize four different sets of isatin-quinazoline (6a–f and 7a–e)/phthalazine (8a–f)/Quinoxalines (9a–f) hybrids. The antiproliferative activity of the target hybrids was assessed towards HT-29 (colon), ZR-75 (breast) and A-549 (lung) human cancer cell lines. Hybrids 8b–d emerged as the most active anti proliferative congener in this study. Compound 8c induced apoptosis via increasing caspase 3/7 activity by about 5-fold in the A-549 human cancer cell line. In addition, it exhibited an increase in the G1 phase and a decrease in the S and G2/M phases in the cell cycle effect assay. Furthermore, it displayed an inhibitory concentration 50% value of 9.5 µM against multidrug-resistant NCI-H69AR lung cancer cell line. The hybrid 8c was also subjected to in vitro metabolic investigations through its incubation with rat liver microsomes and analysis of the resulting metabolites with the aid of liquid chromatography-mass spectrometry.

5. Antioxidant activity¹⁵

Nugumanova G. N et al has been reported the Antioxidant activity of isatin acylhydrazones with sterically hindered phenol fragments. Sterically hindered phenolic isatin acylhydrazones were found to possess high antioxidant activity in model reaction with a free chromogen-radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH).

6. Antimicrobial Activity¹⁶

Patel.A et al has been reported the Synthesis and Antimicrobial Activity of Some New Isatin Derivatives. Some new 3-[(5-benzylidene-2-phenyl)-3, 5-dihydro-4-H-imidazol-4-one-3-(4-bezoylhydrazono)]-indole-2-ones have been synthesized from different isatinhydrazones (II) by condensing with 2-phenyl-5-benzylidene- 3-N (4-acetyl phenyl)-1, 5-dihydro-imidazol-4-one (VII). Their chemical structures have been confirmed by IR, 1HNMR, MASS and by elemental analysis. Investigation of antimicrobial activity of compounds was done by the disk diffusion technique. Among the compounds tested, the compound with 5-Br substitution showed the most favorable antimicrobial activity.

7. Anti HIV activity¹⁷

Rita M et al have been reported the Isatin thiazoline hybrids as dual inhibitors of HIV-1 reverse transcriptase. A series of 3-3-{2-[2-3-methyl-4-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene-2,3-dihydro-1H-indol-2-one derivatives has been designed and synthesized to study their activity on both HIV-1 (Human Immunodeficiency Virus type 1) RT (Reverse Transcriptase) associated functions. These derivatives are analogs of previously reported series whose biological activity and mode of action have been investigated. In this work we investigated the influence of the introduction of a methyl group in the position 3 of the dihydrothiazole ring and of a chlorine atom in the position 5 of the isatin nucleus. The new synthesized compounds are active towards both DNA polymerase and ribonuclease H in the µM range. The nature of the aromatic group in the position 4 of the thiazole was relevant in determining the biological activity.

8. Analgesic activity¹⁸

Rajaram.C et al have been reported the Synthesis and Analgesic Activity of some novel Schiff and mannich base of 5-substituted isatin derivatives. Synthesis and analgesic activity of some novel Schiff and mannich bases isatin derivatives. Methods: a series of novel 3-(4-(2-(substituted benzylideneamino) thiazol-4-yl) phenylimino)-1-((dimethylamino) methyl)-5-fluoroindolin-2-one Schiff and mannich base derivatives were synthesized by using various aromatic aldehydes with isatin derivatives. The chemical structures of all synthesized compounds were confirmed by IR. The results of analgesic activity showed that some of the synthesized compounds were exhibited promising results. H-NMR, Mass spectra and elemental analysis. All the synthesized compounds were screened for its analgesic activity.

9. Anti Alzheimer’s activity¹⁹

Chandra. M et al has been reported the Biological Evaluation of Schiff Bases of New Isatin Derivatives for Anti Alzheimer's Activity. Isatin can be used for synthesis of many heterocyclic compounds having diverse pharmacological activities. Several Isatin derivatives are being developed as promising drugs in the area of central nervous system diseases. In the present study, six novel Isatin derivatives, especially Schiff bases were screened for possible Anti-Alzheimer's activity using the scopolamine model with. Acute oral toxicity, along with in vivo and invitro tests like Radial arm maze (RAM), Morris water maze (MWM), Jumping box test along with assessment of Lipid per oxidation (LPO), Super oxide dismutase (SOD), Catalase and Acetyl choline esterase levels followed by histopathological study of rat brain tissues. Various Schiff bases of Isatin derivatives showed significant anti-amnesic activity as assessed by behavioral test using RAM, MWM and Jumping box test. There was a significant increase (p<0.05) in brain LPO levels in animals treated with scopolamine when compared to scopolamine and Isatin group. There was a significant decrease (p < 0.05) in brain SOD, catalase activity in animals treated with scopolamine when compared to scopolamine and Isatin group. Also, the animals treated with Isatin and scopolamine showed a significantly decreased acetyl cholinesterase activity when compared to scopolamine treated groups. The histopathological study also revealed less amyloid formation in groups treated with Isatin derivatives when compared to control group. The anti amnesic effects of Isatin derivatives demonstrated in the present study may be due to anti-oxidant action. Considering the results of behavioral, biochemical and histopathological studies, we hypothesize that Schiff bases of Isatin derivatives may act directly as a free radical scavenger or regulator to inhibit AChE, oxidative activity and ionic homeostasis imbalance in neurons induced by scopolamine.

10. Hepatoprotective activity²⁰

Tejasree.Ch et al has been reported the Hepatoprotective activity of 1-(4-(Dimethylamino) Benzylidene)-5-(2-Oxoindolin-3-ylidene) Thiocarbohydrazone in rats. The aim of the present study was to evaluate the hepatoprotective activity of 1-(4-(dimethylamino) benzylidene)-5-(2-oxoindolin-3-ylidene) thiocarbohydrazone, a novel isatin derivative against carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Hepatic damage was induced by administration of CCl₄ (1 ml/kg, b.w., p.o.) in combination with liquid paraffin (1:1) as a single dose. The hepatotoxic rats were treated with test compound at doses of 50 or 100 mg/kg for three days and liver damage biomarkers, including activities of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (ALP), and levels of total serum bilirubin (TB) measured in blood samples. Results demonstrated that treatment with test compound at doses of 50 or 100mg/kg to hepatotoxic rats produced a significant dose-dependent reduction of elevated SGOT, SGPT, ALP activities and TB levels indicating a hepatoprotective effect that was confirmed by histopathological examination of liver tissues. The study results confirmed the hepatoprotective activity of 1-(4-(dimethylamino benzylidene)-5-(2-oxoindolin-3-ylidene) thiocarbohydrazone in rats.

CONCLUSION:

In the study of isatin and isatin derivative compounds gives different biological activity. The isatin derivatives used in the treatment of an antimicrobial, anticancer, antiviral, anticonvulsant, anti-inflammatory and analgesic etc. The study of isatin molecule finds most effective treatment of multi diseases. This review is expected to be a comprehensive, authoritative and critical review of the isatin template to the chemistry country.

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Received on 10.02.2021 Modified on 25.02.2021

Res. J. Pharmacology and Pharmacodynamics.2021; 13(2):59-62.

DOI: 10.52711/2321-5836.2021.00013

5. Antioxidant activity15

5. Antioxidant activity¹⁵