• KOSARAJU LAHARI Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy, Telangana, India.
  • RAJA SUNDARARAJAN Department of Pharmaceutical Chemistry, GITAM Institute of Pharmacy, GITAM University, Visakhapatnam, Andhra Pradesh, India.



5-Nitroisatin, Indole-2, 3-dione, Schiff base, Mannich base, Anti-tubercular activity, Anti-microbial activity


Objective: Isatins have emerged as antimicrobial agents due to their broad spectrum of in vitro and in vivo antimicrobial activities. In addition, thiazolidinone also reported to possess various biological activities particularly antimicrobial activity. Due to the importance, we planned to synthesize compounds with isatin functionality coupled with thiazolidinone as possible antitubercular and antimicrobial agents which could furnish better therapeutic results.

Methods: In vitro Mycobacterium tuberculosis method and agar streak dilution test are used to estimate antitubercular and antimicrobial potency of title analogs, respectively. Minimum inhibitory concentration of entire title compounds was determined against all tested microorganism such as M. tuberculosis, four Gram-positive, three Gram-negative bacteria, and two fungi.

Results: A series of new thiazolidinone substituted Schiff and Mannich bases of 5-nitroisatins were designed and synthesized by a multistep synthesis from isatin. Structures of synthesized compounds are characterized using Fourier-transform infrared, proton nuclear magnetic resonance, mass spectroscopy, and bases of elemental analysis. Mild to good antitubercular and antimicrobial activity was showed by synthesized 5-nitroisatin analogs. The relationship between the biological activity and the functional group variation of the tested compounds was discussed.

Conclusion: 3-(4-(3-(4-Aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethyl amino)methyl)-5-nitroindolin-2-one 6 and 3-(4-(3- (2-aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethylamino)methyl)-5-nitroindolin-2-one 13 were found to be the most potent compounds of this series which might be extended as a novel class of antimicrobial agents.


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Halezeroğlu S, Okur E. Thoracic surgery for haemoptysis in the context of tuberculosis: What is the best management approach? J Thorac Dis 2014;6:182-5.

Golden MP, Vikram HR. Extrapulmonary tuberculosis: An overview. Am Fam Physician 2005;72:1761-8.

Klemens SP, DeStefano MS, Cynamon MH. Therapy of multidrug-resistant tuberculosis: Lessons from studies with mice. Antimicrob Agents Chemother 1993;37:2344-7.

Maste MM, Jeyarani P, Kalekar MC, Bhat AR. Synthesis and evaluation of benzimidazole derivatives for anti-tubercular and anti-microbial activities. Asian J Res Chem 2011;4:1055-8.

Parish T, Stoker NG. Mycobacteria: Bugs and bugbears (two steps forward and one step back). Mol Biotechnol 1999;13:191-200.

Zumla A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov 2013;12:388-404.

Klopper M, Warren RM, Hayes C, Gey van Pittius NC, Streicher EM, Müller B, et al. Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa. Emerg Infect Dis 2013;19:449-55.

Slomski A. South Africa warns of emergence of “totally” drug-resistant tuberculosis. J Am Med Assoc 2013;309:1097-8.

Prasad R. Management of multi-drug resistant tuberculosis: Practitioner’s view point. Indian J Tuberc 2007;54:3-11.

Saravanan G, Alagarsamy V, Kumar PD, Selvam TP, Prakash CR. Isatin-a potent anticonvulsant agent. Eur J Biomed Pharm Sci 2017;4:277-82.

Chinnasamy RP, Sundararajan R, Govidaraj S. Synthesis, analgesic, anti-inflammatory and in vitro antimicrobial studies of some novel Schiff and mannich base of 5-substituted isatin derivatives. Int J Pharm Pharm Sci 2014;6:160-6.

Penthala NR, Yerramreddy TR, Madadi NR, Crooks PA. Synthesis and in vitro evaluation of N-alkyl-3-hydroxy-3-(2-imino-3-methyl-5- oxoimidazolidin-4-yl)indolin-2-one analogs as potential anticancer agents. Bioorg Med Chem Lett 2010;20:4468-71.

Prakash CR, Raja S, Saravanan G. Synthesis and anti-epileptic activity of some novel 3-(4-(4-(substitutedbenzylideneamino)-5-mercapto- 4-1,2,4-triazole-3-yl)phenylimino)-1- ((dimethylamino)methyl)-5- fluoroindolin-2-one derivatives. Int J Pharm Pharm Sci 2014;6:539-44.

Selvam P, Chandramohan M, De Clercq E, Witvrouw M, Pannecouque C. Synthesis and anti-HIV activity of 4-[(1,2-dihydro-2-oxo-3H-indol-3- ylidene) amino]-N(4,6-dimethyl-2-pyrimidinyl)-benzene sulfonamide and its derivatives. Eur J Pharm Sci 2001;14:313-6.

Saravanan G, Alagarsamy V, Dineshkumar P. Anticonvulsant activity of novel 1-(morpholinomethyl)-3-substituted isatin derivatives. Bull Fac Pharm (Cairo Univ) 2014;52:115-24.

Karthik K, Priyanka KB, Manjula S, Sammaiah G. Synthesis and evaluation of new bis-isatin derivatives for antioxidant activity. Int J Pharm Pharm Sci 2013;5:224-7.

González A, Quirante J, Nieto J, Almeida MR, Saraiva MJ, Planas A, et al. Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors. Bioorg Med Chem Lett 2009;19:5270-3.

Chinnasamy RP, Sundararajan R, Govindaraj S. Synthesis, characterization and anti-convulsant activity of novel Schiff base of isatin derivatives. Int J Pharm Pharm Sci 2010;2:177-81.

Ahmed MN, Hassan MA, Mashooq AB, Mohamed AA, Abd EG. Microwave-assisted synthesis and anti-microbial activity of some novel isatin Schiff bases linked to nicotinic acid via certain amino acid bridge. J Chem 2015;364841:1-8.

Amani AM. Synthesis, characterization and biological activities of some novel isatin derivatives. Bulg Chem Commun 2014;46:795-800.

Brkić DR, Božić AR, Marinković AD, Milčić MK, Prlainović NŽ, Assaleh FH, et al. Detailed solvent, structural, quantum chemical study and antimicrobial activity of isatin schiff base. Spectrochim Acta A Mol Biomol Spectrosc 2018;196:16-30.

Kalawati M, Sudesh K, Jitender MK, Amita M, Chetan S, Harsh P. One pot three component synthesis of spiro[indolo-3,10′-indeno[1,2-b] quinolin]-2,4,11′-triones as a new class of anti-fungall and anti-microbial agents. Chin Chem Lett 2017;28:136-42.

Mahmoud FA, Wagdy ME, Riham FG, Marwa MA, Mahmoud ME, Nagwa MA, et al. Novel indole-thiazolidinone conjugates: Design, synthesis and whole-cell phenotypic evaluation as a novel class of anti-microbial agents. Eur J Med Chem 2018;160:49-60.

Prakash CR, Raja S, Selvam TP, Saravanan G, Karthick V, Kumar PD. Synthesis and anti-microbial activities of some novel Schiff bases of 5-substituted isatin derivatives. Rasayan J Chem 2009;2:960-8.

Rani PJ, Pandiyan MS, Selvi AS, Aruna A, Venkatesan N. Synthesis, characterization and anti-microbial activity of Schiff and mannich bases of isatin derivatives. World J Pharm Pharm Sci 2017;6:1259-67.

Prakash C, Raja S, Saravanan G. Synthesis, analgesic, anti-inflammatory and in vitro antimicrobial studies of some novel Schiff and mannich base of 5-substituted isatin derivatives. Int J Pharm Pharm Sci 2014;10:160-6.

Al-Mudhafar MM. Synthesis, characterization and preliminary antimicrobial evaluation of new Schiff bases of ampicillin and amoxicillin derived from isatin derivatives. Int J Pharm Pharm Sci 2016;5:113-6.

Metwally NH, Radwan IT, El-Serwy WS, Mohamed MA. Design, synthesis, DNA assessment and molecular docking study of novel 2-(pyridin-2-ylimino)thiazolidin-4-one derivatives as potent antifungal agents. Bioorg Chem 2019;84:456-67.

Gawronska-Grzywacz M, Popiołek L, Natorska-Chomicka D, Piątkowska-Chmiel I, Izdebska M, Herbet M, et al. Novel 2,3disubstituted 1,3thiazolidin4one derivatives as potential antitumor agents in renal cell adenocarcinoma. Oncol Rep 2019;41:693-701.

Bhutani R, Pathak DP, Kapoor G, Husain A, Iqbal MA. Novel hybrids of benzothiazole-1,3,4-oxadiazole-4-thiazolidinone: Synthesis, in silico ADME study, molecular docking and in vivo anti-diabetic assessment. Bioorg Chem 2019;83:6-19.

Abo-Ashour MF, Eldehna WM, George RF, Abdel-Aziz MM, Elaasser MM, Abdel Gawad NM, et al. Novel indole-thiazolidinone conjugates: Design, synthesis and whole-cell phenotypic evaluation as a novel class of antimicrobial agents. Eur J Med Chem 2018;160:49-60.

Fesatidou M, Zagaliotis P, Camoutsis C, Petrou A, Eleftheriou P, Tratrat C, et al. 5-adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design, synthesis, molecular docking and evaluation. Bioorg Med Chem 2018;26:4664-76.

Siddiqui N, Alam MS, Stables JP. Synthesis and anticonvulsant properties of 1-(amino-N-arylmethanethio)-3-(1-substituted benzyl-2, 3-dioxoindolin-5-yl) urea derivatives. Eur J Med Chem 2011;46:2236-42.

National Committee for Clinical Laboratory Standards. Antimycobacterial Susceptibility Testing for M. tuberculosis. Proposed Standards M24-T. Villanova, PA: National Committee for Clinical Laboratory Standards; 1995.

Sriram D, Yogeeswari P, Dinakaran M, Thirumurugan R. Antimycobacterial activity of novel 1-(5-cyclobutyl-1,3-oxazol-2- yl)-3-(substituted)phenyl/pyridyl thiourea endowed with high activity toward multi drug resistant tuberculosis. J Antimicrob Chemother 2007;59:1194-6.

Hawkey PM, Lewis DA. Medical Bacteriology: A Practical Approach. 1st ed. New York: Oxford University Press; 1990. p. 181-94.



How to Cite

KOSARAJU LAHARI, and RAJA SUNDARARAJAN. “DESIGN AND SYNTHESIS OF NOVEL 1-((DIMETHYLAMINO)METHYL)-3-(4-(3-(SUBSTITUTE DPHENYL)-4-OXOTHIAZOLIDIN-2-YL)PHENYLIMINO)-5-NITROINDOLIN-2-ONES AS POTENT ANTITUBERCULAR AGENTS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 12, no. 5, May 2019, pp. 200-7, doi:10.22159/ajpcr.2019.v12i5.31965.



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