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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Synthesis, Spectroscopic, In-vitro and Computational Analysis of Hydrazones as Potential Antituberculosis Agents: (Part-I)

Author(s): Bapu R. Thorat*, Deepa Rani, Ramesh S. Yamgar and Suraj N. Mali*

Volume 23, Issue 5, 2020

Page: [392 - 401] Pages: 10

DOI: 10.2174/1386207323999200325125858

Price: $65

Abstract

Background: Since the last few decades, the healthcare sector is facing the problem of the development of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) infections all over the world. Regardless of the current healthcare progress for the treatment of mycobacterial infections, we are still unable to control addition of every year 9 million new cases of tuberculosis (TB).

Objective: We had an objective to synthesize some novel hydrazones, which were further subjected to characterization, Photoluminescence study, in vitro anti-mycobacterium testing and in silico ADMET predictions.

Methods: Some new hydrazone derivatives have been successfully prepared by the condensation reaction in the present study. All the compounds were characterized by using FTIR, NMR, UV, Fluorescence spectroscopic techniques.

Results: All our newly synthesized compounds showed strong electronic excitation at 292.6 – 319.0 nm and displayed more intense emissions in the 348 – 365 nm regions except compound 3i. The newly synthesized hydrazones 3a, 3b, 3f and 3g were found to be the most active compounds and showed MIC (Minimum inhibitory concentrations) values of 12.5 μg/mL.

Conclusion: In the realm of development of more potent, effective, safer and less toxic antituberculosis agents; our current study would definitely help the medicinal chemists to develop potent analogues containing hydrazine motifs in them.

Keywords: Hydrazide-hydrazones, antituberculosis activity, in silico analysis, tuberculosis, synthesis, potent analogues.

« Previous Next »
[1]
Raza, A.; Jacobson, B.A.; Benoit, A.; Patel, M.R.; Jay-Dixon, J.; Hiasa, H.; Ferguson, D.M.; Kratzke, R.A. Novel acridine-based agents with topoisomerase II inhibitor activity suppress mesothelioma cell proliferation and induce apoptosis. Invest. New Drugs, 2012, 30(4), 1443-1448.
[http://dx.doi.org/10.1007/s10637-011-9720-7] [PMID: 21789510]
[2]
Delgado, J.L.; Hsieh, C.M.; Chan, N-L.; Hiasa, H. Topoisomerases as anticancer targets. Biochem. J., 2018, 475(2), 373-398.
[http://dx.doi.org/10.1042/BCJ20160583] [PMID: 29363591]
[3]
Pitta, M.G.R.; Souza, E.S.; Barros, F.W.A.; Filho, M.O.M.; Pessoa, C.O.; Hernandes, M.Z.; Lima, M.C.A.; Galdino, S.L.; Pitta, I.R. Synthesis and in vitro anticancer activity of novel thiazacridine derivatives. Med. Chem. Res., 2013, 22, 2421-2429.
[http://dx.doi.org/10.1007/s00044-012-0236-2]
[4]
Barros, F.W.A.; Silva, T.G.; da Rocha Pitta, M.G.; Bezerra, D.P.; Costa-Lotufo, L.V.; de Moraes, M.O.; Pessoa, C.; de Moura, M.A.; de Abreu, F.C.; de Lima, Mdo.C.; Galdino, S.L.; Pitta, Ida.R.; Goulart, M.O. Synthesis and cytotoxic activity of new acridine-thiazolidine derivatives. Bioorg. Med. Chem., 2012, 20(11), 3533-3539.
[http://dx.doi.org/10.1016/j.bmc.2012.04.007] [PMID: 22546208]
[5]
Chagas, M.; Cordeiro, N.; Marques, K.; Rocha Pitta, M.G.; Rêgo, M.; Lima, M.; Pitta, M.; Pitta, I.R. New thiazacridine agents: Synthesis, physical and chemical characterization, and in vitro anticancer evaluation. Hum. Exp. Toxicol., 2017, 36(10), 1059-1070.
[http://dx.doi.org/10.1177/0960327116680274] [PMID: 27895099]
[6]
Belmont, P.; Bosson, J.; Godet, T.; Tiano, M. Acridine and acridone derivatives, anticancer properties and synthetic methods: where are we now? Anticancer. Agents Med. Chem., 2007, 7(2), 139-169.
[http://dx.doi.org/10.2174/187152007780058669] [PMID: 17348825]
[7]
Lang, X.; Li, L.; Chen, Y.; Sun, Q.; Wu, Q.; Liu, F.; Tan, C.; Liu, H.; Gao, C.; Jiang, Y. Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents. Bioorg. Med. Chem., 2013, 21(14), 4170-4177.
[http://dx.doi.org/10.1016/j.bmc.2013.05.008] [PMID: 23735826]
[8]
Lafayette, E.A.; Vitalino de Almeida, S.M.; Pitta, M.G.; Carneiro Beltrão, E.I.; da Silva, T.G.; Olímpio de Moura, R.; Pitta, Ida.R.; de Carvalho, L.B., Jr; de Lima, Mdo.C. Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine and imidazacridine derivatives. Molecules, 2013, 18(12), 15035-15050.
[http://dx.doi.org/10.3390/molecules181215035] [PMID: 24322489]
[9]
Cholewiński, G.; Dzierzbicka, K.; Kołodziejczyk, A.M. Natural and synthetic acridines/acridones as antitumor agents: their biological activities and methods of synthesis. Pharmacol. Rep., 2011, 63(2), 305-336.
[http://dx.doi.org/10.1016/S1734-1140(11)70499-6] [PMID: 21602588]
[10]
Paulíková, H.; Vantová, Z.; Hunáková, L.; Čižeková, L.; Čarná, M.; Kožurková, M.; Sabolová, D.; Kristian, P.; Hamul’aková, S.; Imrich, J. DNA binding acridine-thiazolidinone agents affecting intracellular glutathione. Bioorg. Med. Chem., 2012, 20(24), 7139-7148.
[http://dx.doi.org/10.1016/j.bmc.2012.09.068] [PMID: 23122936]
[11]
Yuan, Z.; Chen, S.; Chen, C.; Chen, J.; Chen, C.; Dai, Q.; Gao, C.; Jiang, Y. Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine derivatives as dual PARP and Topo inhibitors for cancer therapy. Eur. J. Med. Chem., 2017, 138, 1135-1146.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.050] [PMID: 28763648]
[12]
Souibgui, A.; Gaucher, A.; Marrot, J.; Bourdreux, F.; Aloui, F.; Hassine, B.B.; Prim, D. New series of acridines and phenanthrolines: synthesis and characterization. Tetrahedron, 2014, 70, 3042-3048.
[http://dx.doi.org/10.1016/j.tet.2014.02.067]
[13]
de Almeida, S.M.V.; Ribeiro, A.G.; de Lima Silva, G.C.; Ferreira Alves, J.E.; Beltrão, E.I.C.; de Oliveira, J.F.; de Carvalho, L.B.; Alves de Lima, M.D.C. DNA binding and Topoisomerase inhibition: How can these mechanisms be explored to design more specific anticancer agents? Biomed. Pharmacother., 2017, 96, 1538-1556.
[http://dx.doi.org/10.1016/j.biopha.2017.11.054] [PMID: 29174576]
[14]
Viegas-Junior, C.; Danuello, A.; da Silva Bolzani, V.; Barreiro, E.J.; Fraga, C.A.M. Molecular hybridization: a useful tool in the design of new drug prototypes. Curr. Med. Chem., 2007, 14(17), 1829-1852.
[http://dx.doi.org/10.2174/092986707781058805] [PMID: 17627520]
[15]
Chadha, N.; Bahia, M.S.; Kaur, M.; Silakari, O. Thiazolidine-2,4-dione derivatives: programmed chemical weapons for key protein targets of various pathological conditions. Bioorg. Med. Chem., 2015, 23(13), 2953-2974.
[http://dx.doi.org/10.1016/j.bmc.2015.03.071] [PMID: 25890697]
[16]
Rupainwar, R.; Pandey, J.; Smrirti, S.; Ruchi, R. The Importance and Applications of Knoevenagel Reaction (Brief Review). Orient. J. Chem., 2019, 35(1), 423-429.
[http://dx.doi.org/10.13005/ojc/350154]
[17]
Gu, C-L.; Liu, L.; Sui, Y.; Zhao, J-L.; Wanga, D.; Chen, Y-J. Highly enantioselective Michael additions of a-cyanoacetate with chalcones catalyzed by bifunctional cinchona-derived thiourea organocatalyst. Tetrahedron Asymmetry, 2007, 18, 455-463.
[http://dx.doi.org/10.1016/j.tetasy.2007.02.016]
[18]
Zaliznaya, E.V.; Farat, O.K.; Varenichenko, S.A.; Mazepa, A.V.; Markov, V.I. Functionalization of tetra- and octahydroacridine derivatives through Michael addition. Tetrahedron Lett., 2016, 57, 3485-3487.
[http://dx.doi.org/10.1016/j.tetlet.2016.06.096]
[19]
Gao, C.; Liu, F.; Luan, X.; Tan, C.; Liu, H.; Xie, Y.; Jin, Y.; Jiang, Y. Novel synthetic 2-amino-10-(3,5-dimethoxy)benzyl-9(10H)-acridinone derivatives as potent DNA-binding antiproliferative agents. Bioorg. Med. Chem., 2010, 18(21), 7507-7514.
[http://dx.doi.org/10.1016/j.bmc.2010.08.058] [PMID: 20863710]
[20]
Janovec, L.; Kožurková, M.; Sabolová, D.; Ungvarský, J.; Paulíková, H.; Plšíková, J.; Vantová, Z.; Imrich, J. Cytotoxic 3,6-bis((imidazolidinone)imino)acridines: synthesis, DNA binding and molecular modeling. Bioorg. Med. Chem., 2011, 19(5), 1790-1801.
[http://dx.doi.org/10.1016/j.bmc.2011.01.012] [PMID: 21315610]
[21]
Rajendran, V.; Jain, M.V. In vitro tumorigenic assay: colony forming assay for cancer stem cells. In: Cancer Stem Cells, Methods in Molecular Biology; Papaccio, G.; Desiderio, V., Eds.; Humana Press: New York, 2018; Vol. 1692, pp. 89-95.
[http://dx.doi.org/10.1007/978-1-4939-7401-6_8]
[22]
Ghosh, R.; Bhowmik, S.; Bagchi, A.; Das, D.; Ghosh, S. Chemotherapeutic potential of 9-phenyl acridine: biophysical studies on its binding to DNA. Eur. Biophys. J., 2010, 39(8), 1243-1249.
[http://dx.doi.org/10.1007/s00249-010-0577-z] [PMID: 20135310]
[23]
Belmont, P.; Andrez, J-Ch.; Allan, C.S.M. New methodology for acridine synthesis using a rhodium-catalyzed benzannulation. Tetrahedron Lett., 2004, 45, 2783-2786.
[http://dx.doi.org/10.1016/j.tetlet.2004.02.022]
[24]
Demeunynck, M. Antitumour acridines. Expert Opin. Ther. Pat., 2004, 14, 55-70.
[http://dx.doi.org/10.1517/13543776.14.1.55]
[25]
Denny, W.A. Acridine derivatives as chemotherapeutic agents. Curr. Med. Chem., 2002, 9(18), 1655-1665.
[http://dx.doi.org/10.2174/0929867023369277] [PMID: 12171548]
[26]
Grommes, C.; Landreth, G.E.; Heneka, M.T. Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet Oncol., 2004, 5(7), 419-429.
[http://dx.doi.org/10.1016/S1470-2045(04)01509-8] [PMID: 15231248]
[27]
Theocharis, S.; Margeli, A.; Vielh, P.; Kouraklis, G. Peroxisome proliferator-activated receptor-γ ligands as cell-cycle modulators. Cancer Treat. Rev., 2004, 30(6), 545-554.
[http://dx.doi.org/10.1016/j.ctrv.2004.04.004] [PMID: 15325034]
[28]
Alemán-González-Duhart, D.; Tamay-Cach, F.; Correa-Basurto, J.; Padilla-Martínez, I.I.; Álvarez-Almazán, S.; Mendieta-Wejebe, J.E. In silico design, chemical synthesis and toxicological evaluation of 1,3-thiazolidine-2,4-dione derivatives as PPARγ agonists. Regul. Toxicol. Pharmacol., 2017, 86, 25-32.
[http://dx.doi.org/10.1016/j.yrtph.2017.02.008] [PMID: 28202347]
[29]
Nazreen, S.; Alam, M.S.; Hamid, H.; Yar, M.S.; Dhulap, A.; Alam, P.; Pasha, M.A.Q.; Bano, S.; Alam, M.M.; Haider, S.; Kharbanda, C.; Ali, Y.; Pillai, K.K. Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression. Bioorg. Med. Chem. Lett., 2014, 24(14), 3034-3042.
[http://dx.doi.org/10.1016/j.bmcl.2014.05.034] [PMID: 24890090]
[30]
Bhowmik, S.; Bagchi, A.; Ghosh, R. Molecular modelling studies of some 9-arylacridines to elucidate their possible roles in Topoisomerase I inhibition. Int. J. Integr. Biol., 2008, 2, 8-14.
[31]
Castelli, S.; Katkar, P.; Vassallo, O.; Falconi, M.; Linder, S.; Desideri, A. A natural anticancer agent thaspine targets human topoisomerase IB. Anticancer. Agents Med. Chem., 2013, 13(2), 356-363.
[http://dx.doi.org/10.2174/1871520611313020021] [PMID: 22931416]
[32]
Farsani, F.M.; Ganjalikhany, M.R.; Vallian, S. Studies on non-synonymous polymorphisms altering human DNA topoisomerase II-alpha interaction with amsacrine and mitoxantrone: An in silico approach. Curr. Cancer Drug Target, 2017, 17(7), 657-668.
[http://dx.doi.org/10.2174/1568009617666161109142629] [PMID: 27834128]
[33]
Farsani, F.M.; Ganjalikhany, M.R.; Dehbashi, M.; Naeini, M.M.; Vallian, S. Structural basis of DNA topoisomerase II-α (Top2-α) inhibition: a computational analysis of interactions between Top2-α and its inhibitors. Med. Chem. Res., 2016, 25, 1250-1259.
[http://dx.doi.org/10.1007/s00044-016-1567-1]

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