Login Register Cart 0
Generic placeholder image

Anti-Infective Agents

Editor-in-Chief

ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis of Some 5-(substituted benzylidene-2, 4-dioxothiazolidin-3-yl) benzoic Acid Derivatives by Conventional and Microwave-assisted Methods and Evaluation of their Potential as Antimicrobial Agents

Author(s): Karuna S. Shukla, Shailendra Pandey and Pooja Chawla*

Volume 17, Issue 2, 2019

Page: [115 - 129] Pages: 15

DOI: 10.2174/2211352516666181024151213

Abstract

Background: Multiple antibiotic resistant bacteria represent a challenge in the treatment of infections. It is imperative, therefore, that new substances with antimicrobial properties should be searched to fight these microorganisms.

Objective: A series of 5-benzylidene-2, 4-dioxothiazolidin-3-yl benzoic acid derivatives were synthesized and evaluated their antimicrobial potential. The compounds were synthesized by both conventional and microwave synthesizers.

Methods: In this study, a series of 5-benzylidene-2, 4-dioxothiazolidin-3-yl benzoic acid derivatives were synthesized by Knoevenagel condensation of 2, 4-thiazolidinedione with substituted aryl aldehydes followed by substitution of 3-amino group with p-chlorobenzoic acid. All the synthesized compounds were characterized by spectral (FT-IR, mass and 1HNMR) and elemental analysis. The compounds were evaluated for their in-vitro antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria and a fungal strain by agar well diffusion assay method and solid dilution method.

Results: The compounds exhibited appreciable antimicrobial activity. Compound 4-(5-(2- chlorobenzylidene)-2, 4-dioxothiazolidin-3-yl)benzoic acid (3f) expressed potent antimicrobial activities against all of the microbial strains examined in this study with MIC values ranging between 0.6-0.8 µg/mL and diameter of the zone of inhibition between 17.2-19.5 mm at the concentration of 200 µg/mL.

Conclusion: There was a marked decrease in the reaction time, under mild conditions through microwave synthesis wherein it presented a green approach towards syntheses of the thiazolidinedione derivatives. All compounds exhibited mild to moderate antimicrobial activity. The results of tested bioactive assay showed that the nature of the substituent on the phenyl ring significantly influenced the antimicrobial activity. Among the chloro, bromo and methoxy substituted derivatives, chloro derivative possessed the highest activity followed by bromo and then methoxy. The position of the substituents on the arylidene nucleus also affected the activity and it was found that generally ortho-substituted derivatives showed better antimicrobial activity than others.

Keywords: Thiazolidine-2, 4-dione, microwave-assisted synthesis, antibacterial, antifungal, knoevenagel condensation, MW.

Graphical Abstract

[1]
Berber, I.; Cozmus, C.; Atalan, E. Characterization of Staphylococcus species by SDS-PAGE of whole cell and extracellular proteins. Microbiology, 2003, 72, 42-47.
[2]
Bildirici, I.; Sener, A.; Tozlu, I. Further derivatives of 4-benzoyl-1, 5-diphenyl-1H pyrazole-3- carboxylic acid and their antibacterial activities. Med. Chem. Res., 2007, 16, 418-426.
[3]
Sung, W.S.; Jung, H.J.; Park, K.; Kim, H.S.; Lee, Ln. -S. 2, 5-Dimethyl-4-hydroxy-3-(2H)-furanone (DMHF): Antimicrobial compound with cell cycle arrest in nosocomial pathogens. Life Sci., 2007, 80, 586-591.
[4]
Cantello, M.A.; Cawthorne, D.; Haigh, R.M.; Hindley, S.A.; Smith, P.L.; Thurlby, P.L. The synthesis of BRL 49653- a novel and potent anti-hyperglycemic agent. Bioorg. Med. Chem. Lett., 1994, 4(10), 1181-1184.
[5]
Elte, J.W.F.; Blickle, J.F. Thiazolidinediones for the treatment of type- 2 diabetes. Eur. J. Intern. Med., 2007, 18, 18-25.
[6]
Reddy, K.A.; Lohray, B.B.; Bhushan, V.; Bajji, A.C.; Reddy, K.V.; Reddy, P.R.; Krishna, T.H.; Rao, I.N.; Jajoo, H.K.; Rao, N.V.S.; Chakrabarti, M.R.; Kumar, D.T.; Rajagopalan, R.; America, N. Novel antidiabetic and hypolipidemic agents. 5-hydroxyl versus benzyloxy containing chroman derivatives. J. Med. Chem., 1999, 42, 3265-3278.
[7]
Lohray, B.B.; Bhushan, V.; Rao, B.P.; Madhavan, G.R.; Murali, N.; Rao, K.N.; Reddy, A.K.; Rajesh, B.M.; Reddy, P.G.; Chakrabarti, R.; Vikramadithyan, R.K.; Rajagopalan, R.; Mamidi, R.N.V.S.; Jajoo, H.K.; Subramaniam, S. Novel euglycemic and hypolipidemic agents. J. Med. Chem., 1998, 41, 1619-1630.
[8]
Ottana, R.; Maccari, R.; Mortier, J.; Caselli, A.; Amuso, S.; Camici, G.; Rotondo, A.; Wolber, G.; Paoli, P. Biological activity and structure activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells. Eur. J. Med. Chem., 2014, 71, 112-127.
[9]
Prabhakar, C.; Madhusudhan, G.; Sahadev, K.; Maheedhara, R.C.; Sarma, M.R.; Om, R.G.; Chakrabarti, R.; Seshagiri, R.C.; Dileep, K.T.; Rajagopalan, R. Synthesis and biological activity of novel thiazolidinediones. Bioorg. Med. Chem. Lett., 1998, 8, 2725-2730.
[10]
Garg, A.; Chawla, P.; Panjwani, D.; Saraf, S.A. Synthesis of some Novel 5-substituted arylidene 2,4-thiazolidinediones as bioactive agents. Int. J. Pharm. Sci. Nanotech, 2011, 4, 1373-1378.
[11]
Ma, L.; Pei, H.; Lei, L.; He, L.; Chen, J.; Liang, X.; Peng, A.; Ye, H.; Xiang, M.; Chen, L. Structural exploration, synthesis and pharmacological evaluation of Novel 5-benzylidene thiazolidine-2,4-dione derivatives as iNOS inhibitors against inflammatory diseases. Eur. J. Med. Chem., 2015, 92, 178-190.
[12]
Sunduru, N.; Srivastava, K.; Rajakumar, S.; Puri, S.K.; Saxena, J.K.; Chauhan, P.M.S. Synthesis of novel thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-aminoquinoline as potent antimalarials. Bioorg. Med. Chem. Lett., 2009, 19, 2570-2573.
[13]
Reddy, K.A.; Lohray, B.B.; Bhushan, V.; Reddy, A.S.; Kishore, P.H.; Rao, V.V.; Saibaba, V.; Bajji, A.C.; Rajesh, B.M.; Reddy, K.V.; Chakrabarti, R.; Rajagopalan, R. Novel euglycemic and hypolipidemic agents: Part-2 antioxidant moiety as structural motif. Bioorg. Med. Chem. Lett., 1998, 8, 999-1002.
[14]
Hossain, S.U.; Bhattacharya, S. Synthesis of O-prenylated and O-geranylated derivatives of 5-benzylidene 2, 4-thiazolidinediones and evaluation of their free radical scavenging activity as well as effect on some phase II antioxidant/detoxifying enzymes. Bioorg. Med. Chem. Lett., 2007, 17, 1149-1154.
[15]
Mishra, G.; Sachan, N.; Chawla, P. Synthesis and evaluation of thiazolidinedione-coumarin adducts as antidiabetic, anti-inflammatory and antioxidant agents. Lett. Org. Chem., 2015, 12(6), 429-445.
[16]
Huang, J.; Shiau, C.; Yang, J.; Wang, D.; Chiu, H.; Chen, C. Development of small-molecule cyclin D1-ablative agents. J. Med. Chem., 2006, 49, 4684-4689.
[17]
Hafez, H.N.; ElGazzar, A.R.B.A. Synthesis and antitumor activity of substituted traizolo [4,3a] pyrimidin 6-sulphonamide with an incorporated thiazolidinone moiety. Bioorg. Med. Chem. Lett., 2009, 19, 4143-4147.
[18]
Patil, V.; Tilekar, K.; Munj, S.M.; Mohan, R.; Ramaa, C.S. Synthesis and primary cytotoxicity evaluation of new 5-benzylidene-2,4-thiazolidinedione derivatives. Eur. J. Med. Chem., 2010, 45, 4539-4544.
[19]
Fan, Y.H.; Chen, H.; Natarajan, A.; Guo, Y.; Harbinski, F.; Iyasere, J.; Christ, W.; Aktasa, H.; Halperina, J.A. Structure activity requirements for the antiproliferative effect of troglitazone derivatives mediated by depletion of intracellular calcium. Bioorg. Med. Chem. Lett., 2004, 14, 2547-2550.
[20]
Jeon, R.; Park, S.Y. Synthesis and biological activity of benzoxazole containing thiazolidinedione derivatives. Arch. Pharm. Res., 2004, 27, 1099-1105.
[21]
Madhavan, G.R.; Chakrabarti Reddy, R.K.A.; Rajesh, B.M.; Balraju, V.; Rao, P.B.; Rajagopalan, R.; Iqbal, J. Dual PPAR-α and-γ activators derived from novel benzoxazinone containing thiazolidinediones having antidiabetic and hypolipidemic potential. Bioorg. Med. Chem., 2006, 14, 584-591.
[22]
Wang, Z.; Liu, Z.; Lee, W.; Kim, S.N.; Yoon, G.; Cheon, S.H. Design, synthesis and docking study of 5-(substituted benzylidene) thiazolidine-2,4-dione derivatives as inhibitors of protein tyrosine phosphatase 1B. Bioorg. Med. Chem. Lett., 2014, 24, 3337-3340.
[23]
Maccari, R.; Jacomelli, M.; Paoli, P.; Ottana, R.; Ciurleo, R.; Manao, G.; Steindl, T.; Langer, T.; Gabriella, M.; Camici, G.; Annunziata, V.S.S. 5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases. Bioorg. Med. Chem., 2007, 15, 5137-5149.
[24]
Bonde, C.G.; Gaikwad, N.J. Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinediones as antimicrobial agents. Bioorg. Med. Chem., 2004, 12, 2151-2161.
[25]
Avupati, V.R.; Yejella, R.P.; Akula, A.; Guntuku, G.S.; Doddi, B.R.; Vutla, V.R. Synthesis, characterization and biological evaluation of some novel 2,4-thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents as potent anti-HIV-1 agents. Bioorg. Med. Chem. Lett., 2012, 22(20), 6442-6450.
[26]
Alegaon, S.G.; Kallanagouda, R. Alagawadi, Sneha, M.; Pawar, D.; Singh, V.R. Synthesis, characterization, and biological evaluation of thiazolidine-2, 4-dione derivatives. Med. Chem. Res., 2014, 23, 987-994.
[27]
Pandey, V.; Chawla, V.; Saraf, S.K. Comparative study of conventional and microwave-assisted synthesis of some Schiff bases and their potential as antimicrobial agents. Med. Chem. Res., 2012, 21, 844-852.
[28]
Shukla, K.S.; Chawla, P.; Pandey, S. In vitro antimicrobial screening of 2-(4-((2, 4-dioxothiazolidin-5-ylidene) methyl) phenoxy)-N phenylacetamide derivatives. Int. J. Chemtech Res., 2016, 8, 195-200.
[29]
Shukla, K.S.; Chawla, P.; Pandey, S. Synthesis, characterization and screening of thiazolidine-2,4-dione derivatives as antimicrobial agents. Int. J. Microbial Res., 2016, 8, 807-812.
[30]
Loiodice, F.; Pochetti, G. Structural insight into the crucial role of ligand chirality in the activation of PPARs by crystallographic methods. Curr. Top. Med. Chem., 2011, 11, 819-839.
[31]
Kulkarni, S.S.; Gediya, L.K.; Kulkarni, V.M. Three-dimensional quantitative structure activity relationships (3-D-QSAR) of antihyperglycemic agents. Bioorg. Med. Chem., 1999, 7, 1475-1485.
[32]
Markt, P.; Petersen, R.K.; Flindt, E.N.; Kristiansen, K.; Kirchmair, J.; Spitzer, G.; Distinto, S.; Schuster, D.; Wolber, G.; Laggner, C.; Langer, T. Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape and electrostatic similarity screening. J. Med. Chem., 2008, 51, 6303-6317.
[33]
Fukui, Y.; Masui, S.; Osada, S.; Umesono, K.; Motojima, K. A new thiazolidinedione, NC-2100, which is a weak PPAR- Activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice. Diabetes, 2000, 49, 759-767.
[34]
Yanagisawa, H.; Takamura, M.; Yamada, E.; Fujita, S.; Fujiwara, T.; Yachi, M.; Isobe, A.; Hagisawa, Y. Novel oximes having 5-benzyl-2, 4-thiazolidinedione as antihyperglycemic agents : Synthesis and structure activity relationship. Bioorg. Med. Chem. Lett., 2000, 10, 373-375.
[35]
Sonawane, L.V.; Bari, S.B. Synthesis and spectral characterization of some novel N-substituted 2,4-thiazolidinedione. Int. J. Biol. Chem., 2011, 5(1), 68-74.
[36]
Liu, X.; Zheng, C.; Sun, L.; Liu, X.; Piao, H. Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents. Eur. J. Med. Chem., 2011, 46(8), 3469-3473.
[37]
Prasantha, K.B.R.; Karvekar, M.D.; Adhikary, L.; Nanjan, M.J.; Suresh, B. Microwave induced synthesis of the thiazolidine-2, 4-dione motif and the efficient solvent free-solid phase parallel syntheses of 5-benzylidene-thiazolidine-2,4-dione and 5-benzylidene-2-thioxo-thiazolidine-4-one compounds. J. Heterocycl. Chem., 2006, 42, 897-903.
[38]
Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.; Mathe, D. New solvent-free organic synthesis using focused microwaves synthesis. Synthesis, 1998, 9, 1213-1234.
[39]
Varma, R.S.; Dahiya, R.; Kumar, S. Clay catalyzed synthesis of imines and enamines under solvent-free conditions using microwave irradiation. Tetrahedron Lett., 1997, 38, 2039-2042.
[40]
Varma, R.S. Solvent-free accelerated organic syntheses using microwaves. Pure Appl. Chem., 2001, 73(1), 193-198.
[41]
Caddick, S. Microwave organic reactions. Tetrahedron, 1995, 51(38), 10403-10432.
[42]
Galema, S.A. Microwave chemistry. Chem. Soc. Rev., 1997, 26, 233-238.
[43]
Loupy, A. Microwaves in organic synthesis; Wiley: Weinheim, 2002.
[44]
Kidwai, M. Dry media reactions. Pure Appl. Chem., 2001, 73, 147-151.
[45]
Burczyk, A.; Loupy, A.; Bogdal, D.; Petit, A. Improvement in the synthesis of metallophthalocyanines using microwave irradiation. Tetrahedron, 2005, 61, 179-188.
[46]
Maccari, R.; Ottana, R.; Ciurleo, R.; Vigorita, M.G.; Rakowitz, D.; Steindl, T.; Langer, T. Evaluation of in vitro aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones. Bioorg. Med. Chem. Lett., 2007, 17, 3886-3893.
[47]
Bruno, G.; Costantino, L.; Curinga, C.; Maccari, R.; Monforte, F.; Nicolo, F.; Ottana, R.; Vigorita, M.G. Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones. Bioorg. Med. Chem., 2002, 10, 1077-1084.
[48]
Maccari, R.; Ottana, R.; Curinga, C.; Vigorita, M.G.; Rakowitz, D.; Steindl, T.; Langer, T. Structure-activity relationships and molecular modelling of 5-arylidene-2, 4-thiazolidinediones active as aldose reductase inhibitors. Bioorg. Med. Chem., 2005, 13, 2809-2823.
[49]
Sonawane, L.V.; Bari, S.B. Docking studies of few substituted 5-benzyl-2,4-thiazolidinedione with PPAR-γ for antidiabetic activity. Lat. Am. J. Pharm., 2011, 30(3), 568-570.
[50]
Maccari, R.; Ottana, R.; Ciurleo, R.; Vigorita, M.G.; Rakowitz, D.; Steindl, T.; Langer, T. Evaluation of in vitro aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones. Bioorg. Med. Chem. Lett., 2007, 17, 3886-3893.
[51]
Maccari, R.; Ottana, R.; Curinga, C.; Vigorita, M.G.; Rakowitz, D.; Steindl, T.; Langer, T. Structure-activity relationships and molecular modelling of 5-arylidene-2,4-thiazolidinediones active as aldose reductase inhibitors. Bioorg. Med. Chem., 2005, 13, 2809-2823.
[52]
Ottana, R.; Maccari, R.; Mortier, J.; Caselli, A.; Amuso, S.; Camici, G.; Rotondo, A.; Wolber, G.; Paoli, P. Biological activity and structure activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells. Eur. J. Med. Chem., 2014, 71, 112-127.
[53]
Indian Pharmacopoeia, Vol II (P-Z), Controller of Publication, Delhi, A-100. 1996.
[54]
Tortora, G.J.; Funke, B.R.; Case, C.L. Microbiology- An Introduction, 8th ed; Pearson Education Pvt., Ltd.: Singapore, 2009, pp. 588-617.
[55]
Rao, V.; Prasad, R.; Akula, A.; Sankar, G.; Dodde, B.R.; Vutla, V.R.; Adimulam, L.S.; Vyricharla, A.K. Synthesis, characterization and biological evaluation of some novel 2, 4-thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents. Bioorg. Med. Chem. Lett., 2012, 22(20), 6442-6450.
[56]
Hugo, W.B.; Russell, A.D. Pharmaceutical Microbiology, 6th ed; Blackwell science Ltd., 1998, pp. 243-245.
[57]
Kalsi, P.S. Spectroscopy of organic compounds. New age International Ltd; Publishers, 2004.
[58]
Pavia, D.L.; Lampman, G.M.; Kriz, G.S. Introduction to Spectroscopy; Harcourt College Publishers, 2007.
[59]
Kocabalkanli, A.; Ates, O.; Otuk, G. Synthesis of mannich bases of some 2,5-disubstituted 4-thiazolidinones and evaluation of their antimicrobial activities. Archiv. Der. Pharmazie, 2001, 334(2), 35-39.

Rights & Permissions Print Cite
Article Metrics
40
1
© 2024 Bentham Science Publishers | Privacy Policy