Abstract
Isatin and its derivatives is versatile lead molecule for potential bioactive agents and shows wide spectrum of activities. In this study, we evaluated antioxidant, antimicrobial and cytotoxic activity of isatin-3-[N2-(2-benzalaminothiazol-4-yl)] hydrazone derivatives using well defined models. Antioxidant activity of the isatin derivatives (Va-Vj) was evaluated by using the 1, 1-diphenyl-2-picryl hydrazine radicals scavenging assay. The antimicrobial activity is evaluated by cup plate method and anticancer activity is evaluated by MTT assay against HBL-100 & HeLa cell lines. Compound Vh (R = 5-Cl, R1 = OH & R2 = OCH3) showed good antioxidant activity with the IC50 of 8.09 M. In addition Ve and Vi have showned most active antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Escherichia coli with a Zone of Inhibition (mm) 20, 16, 18 and 14, 12, 15 on respective organism at 100 g/disc. The compound Vi have produced a good antifungal activity against Aspergillus niger and Clostridium vericulata with the zone of inhibition values of 9 and 8 mm respectively. These isatin derivatives also among the test compounds, compound Vd (R = 5-Cl, R1 = OH & R2 = OCH3) and compound Vh (R = 5-Cl, R1 = OH & R2 = OCH3) have shown nearly equal cytotoxic activity with IC50 values of 246.53 mM and 247.29 mM against HBL-100 cell lines and HeLa cell lines respectively. From the results, isatin derivatives showed powerful antioxidant activity, antimicrobial and anticancer activity may be due to the halogens substituted at 5th position of isatin. The standard drugs used were ampicillin, clotrimazole, cisplatin and ascorbic acid for antibacterial, antifungal, anticancer and antioxidant respectively.References
Vendemiale G.; Grattagliano, I.; Altomare, E.; An update on the role of free radicals and antioxidant defense in human disease. Int J Clin Lab Res 1999,29, 49-55.
http://dx.doi.org/10.1007/s005990050063
Valko, M.; Rhodes, C. J.; Moncol, J.; Izakovic, M.; Mazur, M.; Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 2006,160, 1-40.
http://dx.doi.org/10.1016/j.cbi.2005.12.009
Leclercq, R. Epidemiological and resistance issues in multidrug-resistant staphylococci and enterococci. Clin Microbiol Infect 2009,15, 224-231.
http://dx.doi.org/10.1111/j.1469-0691.2009.02739.x
Zhang, W.; Locurcio, M.; Lin, C. C.; Jimenez, L. S. Synthesis and reactivity of 2,3-dihydro-1H-pyrrolo[1,2-a]indole derivatives, analogs of the FR900482 and mitomycin C active intermediates. J Het Chem 1996, 33, 1647-1651.
http://dx.doi.org/10.1002/jhet.5570330617
Aydemir, N.; Bilaloglu, R.; Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo. Mutat Res 2003, 537, 43–51.
http://dx.doi.org/10.1016/S1383-5718(03)00049-4
Medvedev, A.; Buneeva, O.; Glover, V. Biological targets for isatin and its analog implicationsfor therapy. Biologics 2007, 1, 151–162.
Manley-King, C. I.; Bergh, J. J.; Petzer, J. P. Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues. Bioorg Med Chem 2011, 19, 261–274.
http://dx.doi.org/10.1016/j.bmc.2010.11.028
Kaur, H.; Kumar, S.; Kumar, A. Synthesis, antipsychotic and anticonvulsant activity of some new pyrazolinyl/isoxazolinylindol-2-ones. Int J Chem Tech Res 2010, 2, 1010–1019.
Venkateshwarlu, E.; Umasankar, K.; Sharavana Bhava B. S.; Venkateshwar Rao, J. Screening of the anticonvulsant activity of some isatin derivatives in experimental seizure models and its effect on brain GABA levels in mice. Am J Pharmacol Sci 2013, 1, 42–46.
Venkateshwar Rao, J.; Venkateshwarlu, E.; Sharavana Bhava B. S.; Umasankar, K. Synthesis and evaluation of neuropharmacological profile of isatin-3-[N2-(2-benzalaminothiazol-4-yl)] hydrazones. Egypt Pharm J 2014;14: 130-138.
Smitha, S.; Pandeya, S. N.; Stables, J. P.; Ganapathy, S. Anticonvulsant and sedative-hypnotic activities of N-acetyl/methyl isatin derivatives. Sci Pharm 2008, 76, 621–636.
http://dx.doi.org/10.3797/scipharm.0806-14
Glaser, M.; Goggi, J.; Smith, G.; Morrison, M.; Luthra, S. K.; Robins, E.; Aboagye, E. O. Improved radio synthesis of the apoptosis marker 18F-ICMT11 including biological evaluation. Bioorg Med Chem Lett 2011, 21, 6945–6949.
http://dx.doi.org/10.1016/j.bmcl.2011.10.001
Praveen, C.; Ayyanar, A.; Perumal, P. T. Practical synthesis, anticonvulsant, and antimicrobial activity of N-allyl and N-propargyl di(indolyl)indolin-2-ones Bioorg Med Chem Lett 2011, 21, 4072–4077.
http://dx.doi.org/10.1016/j.bmcl.2011.04.117
Havrylyuk, D.; Kovach, N.; Zimenkovsky, B.; Vasylenko, O.; Lesyk R. Synthesis and anticancer activity of isatin-based pyrazolines and thiazolidines conjugates. Arch Pharm (Weinheim) 2011, 344, 514–522.
http://dx.doi.org/10.1002/ardp.201100055
Venkateshwarlu, E.; Venkateshwar Rao, J.; Umasankar, K.; Dheeraj, G. Study of anti-inflammatory, analgesic and antipyretic activity of novel isatin derivatives. Asian J Pharm Clin Res 2012, 5, 187–190.
Venkateshwarlu, E.; Venkateshwar Rao, J. Evaluation of anti-diabetic and hypolipidemic activity of isatin derivatives in streptozotocin-nicotinamide induced type II diabetic rats. Adv Biol Res 2013, 7, 288–295.
Venkateshwarlu, E.; Sharavana Bhava, B. S.; Umasankar, K.; Venkateshwar Rao, J. Evaluation of diuretic activity of isatin derivatives in wistar rats. J Pharm Nutr Sci 2013, 3, 141–148.
http://dx.doi.org/10.6000/1927-5951.2013.03.02.5
Prakash, C. R.; Raja, S.; Panneer Selvam, T.; Saravanan, G.; Karthick, V.; Dinesh Kumar, P. Synthesis and antimicrobial activities of some novel Schiff bases of 5-substituted isatin derivatives. Rasâyan J Chem 2009, 2, 960-968.
Lee, D.; Long, S. A.; Murray, J. H.; Adams, J. L.; Nuttall, M. E.; Nadeau DP et al. Potent and Selective Nonpeptide Inhibitors of Caspases 3 and 7. J Med Chem 2001, 44, 2015-2026.
http://dx.doi.org/10.1021/jm0100537
Singh, R.; Fahmi, R. V. N.; Biyala, M. K. Coordination behaviour and bio potency of N and S/O donor ligands with their Palladium (II) and Platinum (II) complexes. J Iranian Chem Soc 2005, 2, 40-46.
http://dx.doi.org/10.1007/BF03245778
Padhy, A. K.; Sahu, S. K.; Panda, P. K.; Kar, D. M.; Misro, P. K. Synthesis and biological evaluation of 1-acetyl-3-(2-acetoxy-3-substituted propyloximino)-indol- 2(3H)- ones. Indian J Chem 2004, 43B, 971-997.
http://dx.doi.org/10.1002/chin.200436103
Pandeya, S. N.; Raja, A. S.; Nath, G. Synthesis and antimicrobial evalution of some 4or 6-chloroisatin derivatives. Indian J Chem 2006, 45B, 494-499.
Choudhari, B. P.; Mulwad, V. V. Synthesis and antimicrobial screening of N-[Coumarin-6-ylamino]thiazolidinone and spiroindolo thiazolidinone derivatives. Indian J Chem 2005, 44B, 74-78.
Pandeya, S. N.; Sriram, D.; Nath, G.; De Clerq, E. Synthesis, antibacterial, antifungal and anti-HIV activities of Schiff and Mannich bases derived from isatin derivatives and N-[4-(4'-chlorophenyl) thiazol-2-yl] thiosemicarbazide. Eur J Pharm Sci 199, 9, 25-31.
http://dx.doi.org/10.1016/s0928-0987(99)00038-x
Pardasani, R. T.; Pardasani, P.; Sherry, D.; Chaturvedi, V. Synthetic and antibacterial studies of rhodanine derivatives with indol -2, 3-dione. Indian J Chem 2001, 40B, 1275-1278.
Singh, G. S.; Singh, T.; Lakhan, R. Synthesis 13 C-NMR and anticonvulsant activity of new isatin based spiroazetidinones. Indian J Chem 1997, 36B, 951-954.
Teitz, Y.; Ronen, D.; Vansover, A.; Stematsky, T.; Riggs, J. L. Inhibition of human immuno deficiency virus by N-methyl isatin-beta4':4'-diethylthiosemicarbazone and N-allylisatin-beta-4':4'-diallythiosemicarbazone. Antivir Res 1994, 24, 305-314
http://dx.doi.org/10.1016/0166-3542(94)90077-9
Patel, P. N.; Patel, H. S. Studies on post reaction products of nove spiroindoline- thiazolidine derivatives. Der Pharm Lett 2011, 3, 307-318.
Madhu, P. B.; Maharaj, K. J.; Brahmeshwari, G.; Sarangapani, M.; Sammaiah, G. Synthesis and Antimicrobial activity of some new isatin derivatives. J Adv Pharm Sci 2011, 1, 20-33.
Bari, S. B.; Agrawal, A. O.; Patil, U. K. Synthesis and Pharmacological Evaluation of Some Novel Isatin Derivatives for Antimicrobial Activity. J Sci I R Iran 2008, 19, 217-221.
Akhaja, T. N.; Raval, J. P. 1, 3-Dihydro-2H-indol-2-ones derivatives: design, synthesis, in vitro antibacterial, antifungal and antitubercular study. Eur J Med Chem 2011, 46, 5573-5579.
http://dx.doi.org/10.1016/j.ejmech.2011.09.023
Suman, A.; Bari, S. B.; Samanta, A. Synthesis and Screening of Some New Isatin Containing Thiazole Derivatives for Antimicrobial Activity. J Appl Chem Res 2014, 8, 31-40.
Cane, A.; Tournaire, M. C.; Barritault, D.; Crumeyrolle-Arias, M. The Endogenous Oxindoles 5-Hydroxyoxindole and Isatin are Antiproliferative and Proapoptotic. Biochem Biophys Res Commun. 2000, 276, 379–384
http://dx.doi.org/10.1006/bbrc.2000.3477
Lee, D.; Long, S. A.; Murray, J. H.; Adams, J. L.; Nuttall, M. E.; Nadeau, D. P.; Kikly, K.; Winkler, J. D.; Sung, C. M.; Ryan, M. D.; Levy, M. A.; Keller, P. M.; De Wolf, W.E. Potent and selective nonpeptide inhibitors of caspases 3 and 7. J Med Chem 2001, 44, 2015–2020.
http://dx.doi.org/10.1021/jm0100537
Hari, H. P.; Umashankar, D.; Wilson, J. Q.; Masami, K.; Hiroshi, S.; Jonathan, R. D. Cytotoxic 3, 5-bis(benzylidene)piperidin-4-ones and N-acyl analogs displaying selective toxicity for malignant cells. Eur J Med Chem 2008, 43, 1–7.
http://dx.doi.org/10.1016/j.ejmech.2007.03.010
Hashem, F. A. Investigation of free radical scavenging activity by ESR for coumarins isolated from Tecoma radicans. J Med Sci 2007, 7, 1027-1032.
http://dx.doi.org/10.3923/jms.2007.1027.1032
Karali, N.; Güzel, O.; Ozsoy, N.; Ozbey, S.; Salman, A. Synthesis of new spiroindolinones incorporating a benzothiazole moiety as antioxidant agents. Eur J Med Chem 2010, 45,1068-1077.
http://dx.doi.org/10.1016/j.ejmech.2009.12.001
Kiran, G.; Sarangapani, M.; Gouthami, T.; Rama Narsimha Reddy, A. Synthesis, characterization, and antimicrobial and antioxidant activities of novel bis-isatin carbohydrazone derivatives. Toxicol Environ Chem 2013, 95, 367-378.
http://dx.doi.org/10.1080/02772248.2013.777605
Khosravi, P.; Jafarkhani K. M.; Nematzadeh G. A.; Bihamta, M. R. A protocol for mass production of Rosa hybrida Iceberg through in vitro propagation. Iranian J Biotech 2007, 100-104
Raghunandan, N.; Devi, M. A.; Sriram, D.; Sarangapani, M. Synthesis and pharmacological screening of some new derivatives of (Z)-[2-(2-substituted benzalamino-4-yl)hydrazono]-indolin-2-ones. Der Pharma Chemica 2010; 96, 106.
Sarangapani, M.; Reddy, V. M. Synthesis and screening of isatin-3-N2- (alkoxyethyloxy) acetyl hydrazones. Indian drugs 1999, 36, 357–362.
John, J.; Bobade, A. S.; Khadse, B. G. Synthesis of some new triazole ring systems from 2, 4-disubstitued thiazole. Indian J Heterocycl Chem 2001, 10, 295–298.
Blois, M. S. Antioxidant determinations by the use of a stable free radical, Nature 1958, 181, 1199-1200.
http://dx.doi.org/10.1038/1811199a0
Hewitt, W.; Vincent, S. Theory and application of Microbiological assay. San Diego: Academic Press, 1989.
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983, 65, 55 63.
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