Generic placeholder image

Anti-Infective Agents

Author(s): Theivendren Panneerselvam, Selvaraj Kunjiappan, Veerachamy Alagarsamy, Govindaraj Saravanan* and Pavadai Parasuraman

DOI: 10.2174/2211352517666190301144054

DownloadDownload PDF Flyer Cite As
Design, Optimization, Synthesis and AntiTB Screening of Benzimidazole Derivatives

Page: [24 - 42] Pages: 19

  • * (Excluding Mailing and Handling)

Abstract

Introduction: A biologically active benzimidazole synthesis was carried out at laboratory scale in order to reduce environmental pollution as well as to identify effective synthetic route.

Methods: In this connection optimization was performed by Central Composite Rotatable Design (CCRD) to develop experimental data through Response Surface Methodology (RSM). The optimization of title analogue was performed by RSM which led us to the identification of high quality of synthetic yield. The effects of four independent parameters [1-5 mol of oxobutanoic acid (X1), 1-5 mol of thionyl chloride (X2), 1-5 mol of imidazol-2-yl-4-oxobutanoyl chloride (X3), and 1-5 mol of 4-nitro aniline (X4) were taken into optimize the synthetic yields of title scaffold.

Results and Conclusion: A result of randomly generated benchmark and real values such as percentage yield, λmax and Retention Time (RT) of title compound are found to be highly significant. The present model is connected to maximize the percentage yield of title scaffold with the developed optimal set. The highly significant benzimidazole was screened for its MTB activity against MTB H37Ra strain by MABA screening.

Keywords: CCRD, RSM, Benzimidazole, % yield, λmax, RT, oxobutonic acid.

Graphical Abstract

[1]
Theivendren, P.; Subramanian, A.; Murugan, I.; Joshi, S.D.; More, U.A. Graph theoretical analysis, insilico modeling, design, and synthesis of compounds containing benzimidazole skeleton as antidepressant agents. Chem. Biol. Drug Des., 2017, 89(5), 714-722.
[http://dx.doi.org/10.1111/cbdd.12894] [PMID: 27797457]
[2]
Tantray, M.A.; Khan, I.; Hamid, H.; Alam, M.S.; Dhulap, A.; Kalam, A. Synthesis of benzimidazole-linked-1,3,4-oxadiazole carboxamides as GSK-3β inhibitors with in vivo antidepressant activity. Bioorg. Chem., 2018, 77, 393-401.
[http://dx.doi.org/10.1016/j.bioorg.2018.01.040] [PMID: 29421716]
[3]
Mann, J.; Baron, A.; Opoku, B.Y.; Johansson, E.; Parkinson, G.; Kelland, L.R.; Neidle, S. A new class of symmetric bisbenzimidazole-based DNA minor groove binding agents. J. Med. Chem., 2001, 44(2), 138-144.
[http://dx.doi.org/10.1021/jm000297b] [PMID: 11170623]
[4]
Alpan, A.S.; Zencir, S.; Zupkó, I.; Coban, G.; Réthy, B.; Gunes, H.S.; Topcu, Z. Biological activity of bis-benzimidazole derivatives on DNA topoisomerase I and HeLa, MCF7 and A431 cells. J. Enzyme Inhib. Med. Chem., 2009, 24(3), 844-849.
[http://dx.doi.org/10.1080/14756360802420831] [PMID: 18951286]
[5]
Ram, S.; Wise, D.S.; Wotring, L.L.; McCall, J.W.; Townsend, L.B. Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates and related derivatives: a new class of potential antineoplastic and antifilarial agents. J. Med. Chem., 1992, 35(3), 539-547.
[http://dx.doi.org/10.1021/jm00081a016] [PMID: 1738146]
[6]
Novak Jovanović, I.; Jadreško, D.; Miličević, A.; Hranjec, M.; Perin, N. An electrochemical study on the redox chemistry of cyclic benzimidazole derivatives with potent anticancer activity. Electrochim. Acta, 2019, 297, 452-462.
[http://dx.doi.org/10.1016/j.electacta.2018.11.198]
[7]
Cheong, J.E.; Zaffagni, M.; Chung, I.; Xu, Y.; Wang, Y.; Jernigan, F.E.; Zetter, B.R.; Sun, L. Synthesis and anticancer activity of novel water soluble benzimidazole carbamates. Eur. J. Med. Chem., 2018, 144, 372-385.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.037] [PMID: 29288939]
[8]
Andrzejewska, M.; Yépez-Mulia, L.; Cedillo-Rivera, R.; Tapia, A.; Vilpo, L.; Vilpo, J.; Kazimierczuk, Z. Synthesis, antiprotozoal and anticancer activity of substituted 2-trifluoromethyl- and 2-pentafluoroethylbenzimidazoles. Eur. J. Med. Chem., 2002, 37(12), 973-978.
[http://dx.doi.org/10.1016/S0223-5234(02)01421-6] [PMID: 12660022]
[9]
Snehlata, Y.; Balasubramanian, N.; Siong, M.L.; Kalavathy, R.; Mani, V.; Syed, A.A.S.; Abhishek, M. Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of benzimidazole derivatives, Egypt. J. Basic Appl. Sci., 2018, 5(1), 100-109.
[10]
El-Masry, A.H.; Fahmy, H.; Ali Abdelwahed, S. Synthesis and antimicrobial activity of some new benzimidazole derivatives. Molecules, 2000, 5(12), 1429-1438.
[http://dx.doi.org/10.3390/51201429]
[11]
Chaturvedi, A.K.; Verma, A.K.; Thakur, J.P.; Roy, S.; Bhushan, T.S.; Kumar, B.S.; Khwaja, S.; Sachan, N.K.; Sharma, A.; Chanda, D.; Shanker, K.; Saikia, D.; Negi, A.S. A novel synthesis of 2-arylbenzimidazoles in molecular sieves-MeOH system and their antitubercular activity. Bioorg. Med. Chem., 2018, 26(15), 4551-4559.
[http://dx.doi.org/10.1016/j.bmc.2018.07.049] [PMID: 30097361]
[12]
Cheng, J.; Xie, J.; Luo, X. Synthesis and antiviral activity against Coxsackie virus B3 of some novel benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2005, 15(2), 267-269.
[http://dx.doi.org/10.1016/j.bmcl.2004.10.087] [PMID: 15603937]
[13]
Bird, M.J.; Silvestri, A.P.; Dawson, P.E. Expedient on-resin synthesis of peptidic benzimidazoles. Bioorg. Med. Chem. Lett., 2018, 28(16), 2679-2681.
[http://dx.doi.org/10.1016/j.bmcl.2018.04.062] [PMID: 29739642]
[14]
Liu, L.; Shen, Y.F.; Hu, Y.; Lu, J.F. Antiviral effect of 7-(4-benzimidazole-butoxy)-coumarin on rhabdoviral clearance via Nrf2 activation regulated by PKCα/β phosphorylation. Fish Shellfish Immunol., 2018, 83, 386-396.
[http://dx.doi.org/10.1016/j.fsi.2018.09.054] [PMID: 30243774]
[15]
Roth, T.; Morningstar, M.L.; Boyer, P.L.; Hughes, S.H.; Buckheit, R.W., Jr; Michejda, C.J. Synthesis and biological activity of novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 2-Aryl-substituted benzimidazoles. J. Med. Chem., 1997, 40(26), 4199-4207.
[http://dx.doi.org/10.1021/jm970096g] [PMID: 9435891]
[16]
Rida, S.M.; El-Hawash, S.A.; Fahmy, H.T.; Hazzaa, A.A.; El-Meligy, M.M. Synthesis of novel benzofuran and related benzimidazole derivatives for evaluation of in vitro anti-HIV-1, anticancer and antimicrobial activities. Arch. Pharm. Res., 2006, 29(10), 826-833.
[http://dx.doi.org/10.1007/BF02973901] [PMID: 17121175]
[17]
Chimirri, A.; Grasso, S.; Monforte, P.; Rao, A.; Zappalà, M.; Monforte, A.M.; Pannecouque, C.; Witvrouw, M.; Balzarini, J.; De Clercq, E. Synthesis and biological activity of novel 1H,3H-thiazolo[3,4-a]benzimidazoles: non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors. Antivir. Chem. Chemother., 1999, 10(4), 211-217.
[http://dx.doi.org/10.1177/095632029901000405] [PMID: 10480739]
[18]
Valdez, J.; Cedillo, R.; Hernández-Campos, A.; Yépez, L.; Hernández-Luis, F.; Navarrete-Vázquez, G.; Tapia, A.; Cortés, R.; Hernández, M.; Castillo, R. Synthesis and antiparasitic activity of 1H-benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2002, 12(16), 2221-2224.
[http://dx.doi.org/10.1016/S0960-894X(02)00346-3] [PMID: 12127542]
[19]
Farahat, A.A.; Ismail, M.A.; Kumar, A.; Wenzler, T.; Brun, R.; Paul, A.; Wilson, W.D.; Boykin, D.W. Indole and benzimidazole bichalcophenes: synthesis, DNA binding and antiparasitic activity. Eur. J. Med. Chem., 2018, 143, 1590-1596.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.056] [PMID: 29126729]
[20]
Khalid, M.; Waleed, H.; Hammad, I.; Bushra, M.; Brendan, T.; Zareen, A.; Isabel, R.; Robert, J.B. Synthesis, DNA binding and antibacterial activity of metal(II) complexes of a benzimidazole Schiff base. Polyhedron, 2019, 157(1), 326-334.
[21]
Paramashivappa, R.; Phani Kumar, P.; Subba Rao, P.V.; Srinivasa Rao, A. Design, synthesis and biological evaluation of benzimidazole/benzothiazole and benzoxazole derivatives as cyclooxygenase inhibitors. Bioorg. Med. Chem. Lett., 2003, 13(4), 657-660.
[http://dx.doi.org/10.1016/S0960-894X(02)01006-5] [PMID: 12639552]
[22]
Nakano, H.; Inoue, T.; Kawasaki, N.; Miyataka, H.; Matsumoto, H.; Taguchi, T.; Inagaki, N.; Nagai, H.; Satoh, T. Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action. Bioorg. Med. Chem., 2000, 8(2), 373-380.
[http://dx.doi.org/10.1016/S0968-0896(99)00291-6] [PMID: 10722160]
[23]
Li, Y.F.; Wang, G.F.; He, P.L.; Huang, W.G.; Zhu, F.H.; Gao, H.Y.; Tang, W.; Luo, Y.; Feng, C.L.; Shi, L.P.; Ren, Y.D.; Lu, W.; Zuo, J.P. Synthesis and anti-hepatitis B virus activity of novel benzimidazole derivatives. J. Med. Chem., 2006, 49(15), 4790-4794.
[http://dx.doi.org/10.1021/jm060330f] [PMID: 16854087]
[24]
Kuş, C.; Ayhan-Kilcigil, G.; Can Eke, B.; Işcan, M. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver. Arch. Pharm. Res., 2004, 27(2), 156-163.
[http://dx.doi.org/10.1007/BF02980099] [PMID: 15022715]
[25]
Muhammad, T.; Ashik, M.; Fazal, R.; Sajjad, A.; Mohamed, I.; Noor, B.A. Synthesis, antiglycation and antioxidant potentials of benzimidazole derivatives. J. King Saud. Univ. Sci., 2020, 32(1), 191-194.
[26]
Neda, O.A.; Denista, Y.Y.; Anelia, T.M.; Magdalena, S.K.B.; Virginia, I.T.; Nadya, G.H.A.; Vera, A.H. Design, synthesis, antioxidant properties and mechanism of action of new N,N′-disubstituted benzimidazole-2-thione hydrazone derivatives. J. Mol. Struct., 2018, 1165, 162-176.
[http://dx.doi.org/10.1016/j.molstruc.2018.03.119]
[27]
Navarrete-Vázquez, G.; Moreno-Diaz, H.; Aguirre-Crespo, F.; León-Rivera, I.; Villalobos-Molina, R.; Muñoz-Muñiz, O.; Estrada-Soto, S. Design, microwave-assisted synthesis, and spasmolytic activity of 2-(alkyloxyaryl)-1H-benzimidazole derivatives as constrained stilbene bioisosteres. Bioorg. Med. Chem. Lett., 2006, 16(16), 4169-4173.
[http://dx.doi.org/10.1016/j.bmcl.2006.05.082] [PMID: 16784847]
[28]
Wijngaard, H.H.; Brunton, N. The optimisation of solid-liquid extraction of antioxidants from apple pomace by response surface methodology. J. Food Eng., 2010, 96(1), 134-140.
[http://dx.doi.org/10.1016/j.jfoodeng.2009.07.010]
[29]
Bezerra, M.A.; Santelli, R.E.; Oliveira, E.P.; Villar, L.S.; Escaleira, L.A. Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta, 2008, 76(5), 965-977.
[http://dx.doi.org/10.1016/j.talanta.2008.05.019] [PMID: 18761143]
[30]
Collins, L.; Franzblau, S.G. Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents Chemother., 1997, 41(5), 1004-1009.
[http://dx.doi.org/10.1128/AAC.41.5.1004] [PMID: 9145860]
[31]
Atkinson, A.; Donev, A.; Tobias, R. Optimum experimental designs with SAS; Oxford university press: Oxford, 1992.