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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Benzo[d]imidazol-5-yl)-5-(substituted)-1,3,4-Oxadiazoles: Synthesis, Anticancer, Antimicrobial and In Silico Studies

Author(s): Naveen Kumar, Swamy Sreenivasa*, Bhuvanesh Sukhlal Kalal, Vasantha Kumar, Bantwal Shivarama Holla, Vinitha Ramanath Pai, Nadigar Revansiddappa Mohan and Shivaraj Govindaiah

Volume 16, Issue 9, 2019

Page: [994 - 1005] Pages: 12

DOI: 10.2174/1570180816666181220123924

Abstract

Background: Cancer is a fatal disease for mankind; continuous research is still going on for the invention of potent anticancer drugs. In this view, 1, 3, 4-Oxadiazoles are privileged molecules which attracted medicinal chemists towards their anticancer properties.

Methods: A new series of benzo[d]imidazol-5-yl)-5-(substituted)-1,3,4-oxadiazole derivatives was synthesized in an efficient ‘one-pot’ nitro reductive cyclization using sodium dithionite as a cyclizing agent by a conventional method with good yield. All the structures of the synthesized molecules were characterized by IR, 1H NMR, HRMS and Mass spectral analysis. Anticancer activity screening against A375 melanoma cancer cell line and MDA-MB-231 breast cancer cell line along with antimicrobial activity were carried out using agar well diffusion method.

Results: Compounds 8a and 8j of the series emerged as potent anticancer agents against A375 melanoma cancer cell line with IC50 47.06 µM and 36.76 µM, respectively. In silico studies also revealed that compounds 8a and 8j showed highest interaction with 2OH4 protein of VEGFR-2 tyrosine kinase. Substantial antibacterial and antifungal activities against the tested microorganism were observed for compounds 8j and 8g.

Conclusion: Potent anticancer property has been observed with 1,3,4-Oxadiazole linked tetrafluro substituted benzene ring 8j indicating that future research on these type of molecules can be continued to improve the anticancer activity.

Keywords: Benzimidazole, oxadiazole, antimicrobial, anticancer, docking, 2OH4 protein, VEGFR-2 tyrosine kinase.

Graphical Abstract
[1]
Aydemir, N.; Bilaloglu, R. Genotoxicity of two anticancer drugs, gemcitabine and topotecan, in mouse bone marrow in vivo. Mutat. Res., 2003, 537, 43-51.
[2]
de Vries, C.; Escobedo, J.A.; Ueno, H.; Houck, K.; Ferrara, N.; Williams, L.T. The fms-like tyrosin kinase, a receptor for vascular endothelial growth factor. Science, 1992, 255, 989-991.
[3]
Shalaby, F.; Rossant, J.; Yamaguchi, T.P.; Gertsenstein, M.; Wu, X.F.; Breitman, M.L.; Schuh, A.C. Failure of blood-island
[4]
Yang, J.C.; Haworth, L.; Sherry, R.M.; Hwu, P.; Schwartzentruber, D.J.; Topalian, S.L.; Steinberg, S.M.; Chen, H.X.; Rosenberg, S.A. A randomized trial of bevacizuma, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med., 2003, 349, 427-434.
[5]
Kubo, K.; Oda, K.; Kaneko, T.; Satoh, H.; Nohara, A. Synthesis of 2-(4-Fluoroalkoxy-2-pyridyl) methyl]sulfinyl]-1H-benzimidazoles as Antiulcer Agents. Chem. Pharm. Bull., 1990, 38, 2853-2858.
[6]
Uchida, M.; Chihiro, M.; Morita, S.; Yamashita, H.; Yamasaki, K.; Kanbe, T.; Yabuuchi, Y.; Nakagawz, K. Synthesis and antiulcer activity of 4-substituted-8-[(2-benzimidazolyl) sulfinylmethyl]-1,2,3,4-tetrahydro quinolines and related compounds. Chem. Pharm. Bull., 1990, 38, 1575-1586.
[7]
Sullivan, D.G.; Pantic, D.; Wallis, A.K. New 1, 2-disubstituted benzimidazoles with high inhibiting effects on poliovirus replication. Experentia, 1967, 23, 704.
[8]
Katiyar, S.K.; Gordon, V.R.; McLaughlin, G.L.; Edlind, T.D. Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence. J. Antimicrob. Chemother., 1994, 38, 2086-2090.
[9]
Beaulieu, P.L.; Bos, M.; Bousquet, Y.; Fazal, G.; Gauthier, J.; Gillard, J.; Goulet, S.; LaPlante, S.; Poupart, M.A.; Lefebvre, S.; McKercher, G.; Pellerin, C.; Austel, V.; Kukolj, G. Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase discovery and preliminary SAR of benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2004, 14, 119-124.
[10]
Vasantha, K.; Basavarajaswamy, G.; Vaishali, M.R.; Boja, P.; Vinitha, P.R.; Shruthi, N.; Mahima, B. Rapid ‘One-pot’ synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents. Bioorg. Med. Chem. Lett., 2015, 25, 1420-1426.
[11]
Redayan, M.A.; Ali, W.B.; Mohammed, A.M. Synthesis, characterization and antibacterial evaluation of some novel benzimidazole derivatives containing 1, 3, 4-thiadiazole moiety. Orient. J. Chem., 2017, 33, 3138-3143.
[12]
Ansari, K.F.; Lal, C. Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents. Eur. J. Med. Chem., 2009, 44, 2294-2299.
[13]
Ansari, K.F.; Lal, C. Synthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives. Eur. J. Med. Chem., 2009, 44, 4028-4033.
[14]
Achar, K.C.S.; Hosamani, K.M.; Seetharamareddy, H.R. In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur. J. Med. Chem., 2010, 45, 2048-2054.
[15]
Kulkarnia, R.G.; Laufer, S.A.; Chandrashekhar, V.M.; Garlapatid, A. Synthesis, p38 kinase inhibitory and anti-inflammatory activity of new substituted benzimidazole derivatives. Med. Chem., 2013, 9, 91-99.
[16]
Gaba, M.; Gaba, P.; Uppal, D.; Dhingra, N.; Bahia, M.S. Om Silakarid.; Mohan, C. Benzimidazole derivatives: Search for GI-friendly anti-inflammatory analgesic agents. Acta Pharm. Sin. B, 2015, 5, 337-342.
[17]
Evans, D.; Hicks, T.A.; Williamson, W.R.N.; Dawson, W.; Meacock, S.C.R.; Kitchen, E.A. Synthesis of a group of 1H-benzimidazoles and their screening for anti-inflammatory activity. Eur. J. Med. Chem., 1996, 31, 635.
[18]
Nakano, H.; Inoue, T.; Kawasaki, N.; Miyataka, H.; Matsumoto, H.; Taguchi, T.; Inagaki, N.; Nagai, H.; Satoh, T. Synthesis of benzimidazole derivatives as anti-allergic agents with 5-lipoxygenase inhibiting action. Chem. Pharm. Bull., 1999, 47, 1573-1578.
[19]
Kus, C.; Ayhan-Kilcigil, G.; Can-Eke, B.; Iscan, M. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver. Arch. Pharm. Res., 2004, 27, 156-163.
[20]
Arora, R.K.; Kaur, N.; Bansaln, Y.; Bansal, G. Novel coumarin benzimidazolederivativesas antioxidants and safer anti-inflammatory agents. Acta Pharm. Sin. B, 2014, 4, 368-375.
[21]
Kerimov, I.; Kilcigil, G.A.; Caneke, B.; Altanlar, N.; Iscan, M. Synthesis, antifungal and antioxidant screening of some novel benzimidazole derivatives. J. Enzyme Inhib. Med. Chem., 2007, 22, 696-701.
[22]
Ates-alago, Z.; Kus, C.; Coban, T. Synthesis and antioxidant properties of novel benzimidazoles containing substituted indole or 1,1,4,4-tetramethyl- 1,2,3,4-tetrahydro-naphthalene fragments. J. Enzyme Inhib. Med. Chem., 2005, 20, 325-331.
[23]
Yadav, S.; Narasimhan, B.; Lim, S.M.; Ramasamy, K.; Vasudevan, M.; Ali, S.S.A.; Mathur, A. Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of benzimidazole derivatives. Egypt. J. Basic Appl. Sci., 2018, 5, 100-109.
[24]
Denny, W.A.; Rewcastle, G.W.; Baguley, B.C. Potential antitumor agents and structure-activity relationships for 2-phenylbenzimidazole-4-carboxamidesa, new class of “minimal” DNA-intercalating agents which may not act via topoisomerase II. J. Med. Chem., 1990, 33, 814.
[25]
Mavrova, A.T.; Anichina, K.K.; Vuchev, D.I.; Tsenov, J.A.; Denkova, P.S.; Kondeva, M.S.; Micheva, M.K. Antihelminthic activity of some newly synthesized 5(6) -(un) substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives. Eur. J. Med. Chem., 2006, 41, 1412-1420.
[26]
Tonelli, M.; Simone, M.; Tasso, B.; Novelli, F.; Boido, V.; Sparatore, F.; Paglietti, G.; Pricl, S.; Giliberti, G.; Blois, S.; Ibba, C.; Sanna, G.; Loddo, R.; Colla, P.L. Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2-phenylbenzimidazole derivatives. Bioorg. Med. Chem. Lett., 2010, 18, 2937-2953.
[27]
Victor, F.; Loncharich, R.; Tang, J.; Wayne, A.S. Synthesis and antiviral activity of c2 analogs of enviroxime: An exploration of the role of critical functionality. J. Med. Chem., 1997, 40, 3478-3483.
[28]
Camacho, J.; Barazarte, A.; Gamboa, N.; Rodrigues, J.; Rojas, R.; Vaisberg, A.; Gilman, R.; Charris, J. Synthesis and biological evaluation of benzimidazole-5-carbohydrazide derivatives as antimalarial, cytotoxic and ant tubercular agents. Bioorg. Med. Chem., 2011, 19, 2023-2029.
[29]
Salahuddin, S.M.; Mazumder, A. Benzimidazoles: A biologically active compounds. Arab. J. Chem., 2017, 10, S157-S173.
[30]
Błaszczak-Swiatkiewicz, K.; Olszewska, P.; Mikiciuk-Olasik, E. Biological approach of anticancer activity of new benzimidazole derivatives. Pharmacol. Res., 2014, 66, 100-106.
[31]
Refaat, H.M. Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur. J. Med. Chem., 2010, 45, 2949-2956.
[32]
Bhat, K.S.; Poojary, B.; Prasad, D.J.; Naik, P.; Holla, B.S. Synthesis and antitumor activity studies of some new fused 1, 2, 4-triazole derivatives carrying 2, 4-dichloro-5-fluorophenyl moiety. Eur. J. Med. Chem., 2009, 44, 5066-5070.
[33]
Refaat, H.M. Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur. J. Med. Chem., 2010, 45, 2949.
[34]
James, N.D.; Growcott, J.W. Zibotentan. Drugs Future, 2009, 34, 624-633.
[35]
Andreani, A.; Granaiola, M.; Leoni, A.; Morigi, R.; Ramballdi, M. Synthesis and anti-tubercular activity of imidazo [2,1-b] thiazoles. Eur. J. Med. Chem., 2001, 36, 743-746.
[36]
Shahzad, S.A.; Yar, M.; Bajda, M.; Jadoon, B.; Khan, Z.A.; Naqvi, S.A.R.; Shaikh, A.J.; Hayat, K.; Mahmmod, A.; Mahmood, N.; Filipek, S. Synthesis and biological evaluation of novel oxadiazole derivatives: A new class of thymidine phosphorylase inhibitors as potential antitumour agents. Bioorg. Med. Chem., 2014, 22, 1008-1015.
[37]
Abadi, A.H.; Eissa, A.A.; Hassan, G.S. Synthesis of novel 1, 3, 4-tri-substituted pyrazole derivatives and their evaluation as anti-tumour and anti-angiogenic agents. Chem. Pharm. Bull., 2003, 51, 838-844.
[38]
Du, Q.R.; Li, D.D.; Pi, Y.Z.; Li, J.R.; Sun, J.; Fang, F.; Zhong, W.Q.; Gong, H.B.; Zhu, H.L. Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents. Bioorg. Med. Chem., 2013, 21, 2286-2297.
[39]
Zheng, Q.Z.; Zhang, X.M.; Xu, Y.; Cheng, K.; Jiao, Q.C.; Zhu, H.L. Synthesis biological evaluation and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumour agents. Bioorg. Med. Chem., 2010, 18, 7836-7841.
[40]
Zhang, X.M.; Qiu, M.; Sun, J.; Zhang, Y.B.; Yang, Y.S.; Wang, X.L.; Zhu, H.L. Synthesis biological evaluation, and molecular docking studies of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer agents. Bioorg. Med. Chem., 2011, 19, 6518-6524.
[41]
Miller, T.A.; Witter, D.J.; Belvedere, S. Histone deacetylase inhibitors. Med. Chem., 2003, 46, 5097-5116.
[42]
Sun, J.; Li, M.H.; Qian, S.S.; Guo, F.J.; Dang, X.F.; Wang, X.M.; Xue, Y.R.; Zhu, H.L. Synthesis and antitumor activity of 1,3,4-oxadiazole possessing 1,4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors. Bioorg. Med. Chem. Letters., 2013, 23, 2876-2879.
[43]
Liu, F.; Luo, X.Q.; Song, B.A.; Bhadury, P.S.; Yang, S.; Jin, L.H.; Xue, W.; Hu, D.Y. Synthesis and antifungal activity of novel sulfoxide derivatives containing trimethoxyphenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moiety. Bioorg. Med. Chem. Lett., 2008, 16, 3632-3640.
[44]
Xu, W.M.; Han, F.F.; He, M.; Hu, D.Y.; He, J.; Yang, S.; Song, B.A. Inhibition of tobaccobacterial wilt with sulfone derivatives containing an 1,3,4-oxadiazole moiety. J. Agric. Food Chem., 2012, 60, 1036-1041.
[45]
Palaska, E.; Sahin, G.; Kelicen, P.; Durlu, N.T.; Altinok, G. Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones. II Farmaco., 2002, 57, 101-107.
[46]
Jakubkiene, V.; Burbuliene, M.M.; Mekuskiene, G.; Udrenaite, E.; Gaidelis, P.; Vainilavicius, P. Synthesis and anti-inflammatory activity of 5-(6-methyl-2-substituted 4-pyrimidinyloxymethyl)-1,3,4-oxadiazole-2-thiones and their 3-morpholinomethyl derivatives. Il Farmaco, 2003, 58, 323-328.
[47]
Abd-Ellah, H.S.; Abdel-Aziz, M.; Shoman, M.E.; Beshr, E.A.M.; Kaoud, T.S.; Ahmed, A.F.F. New 1,3,4-oxadiazole/oxime hybrids: Design, synthesis, antiinflammatory, COX inhibitory activities and ulcerogenic liability. Bioorg. Chem., 2017, 74, 15-29.
[48]
Palaska, E.; Sahin, G.; Kelicen, P.; Durlu, N.T.; Altinok, G. Synthesis and antimicrobial activity of some 1,3,4-oxadiazole derivatives. Farmaco, 2002, 57, 539-542.
[49]
Rane, R.A.; Bangalore, P.K.; Borhade, S.D.; Khandare, P.K. Synthesis and evaluation of novel 4-nitropyrrole-based 1,3,4-oxadiazole derivatives as antimicrobial and anti-tubercular agents. Eur. J. Med. Chem., 2013, 70, 49-58.
[50]
Martinez-Grau, M.A.; Valcarcel, I.C.G.; Early, J.V.; Gessner, R.K.; de Melo, C.S.; de la Nava, E.M.M.; Korkegian, A.; Ovechkina, Y.; Flint, L.; Gravelle, A.; Cramer, J.W.; Desai, P.V.; Street, L.J.; Odingo, J.; Masquelin, T.; Chibale, K.; Parish, T. Synthesis and biological evaluation of aryl-oxadiazoles as inhibitors of Mycobacterium tuberculosis. Bioorganic. Med. Chem. Lett., 2018, 28, 1758-1764.
[51]
Ahsan, M.J.; Samy, J.G.; Khalilullah, H.; Nomani, M.S.; Saraswat, P.; Singh, G.R. Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents. Bioorg. Med. Chem. Lett., 2011, 21, 7246-7250.
[52]
Taha, M.; Rahim, F.; Imran, S.; Ismail, N.H.; Ullah, H.; Selvaraj, M.; Javid, M.T.; Salar, U.; Ali, M.; Khan, K.M. Synthesis, a-glucosidase inhibitory activity and in silico study of tris-indole hybrid scaffold with oxadiazole ring: As potential leads for the management of type-II diabetes mellitus. Bioorg. Chem., 2017, 74, 30-40.
[53]
Nazira, M.; Abbasia, M.A. Aziz-ur-Rehman.; Siddiqui, S.Z.; Khan, K.M.; Kanwal.; Salar, U.; Shahid, M.; Ashraf, M.; Lodhi, M.A.; Khane, F.A. New indole based hybrid oxadiazole scaffolds with N-substituted acetamides: As potent anti-diabetic agents. Bioorg. Chem., 2018, 81, 253-263.
[54]
Shingalapur, R.V.; Hosamani, K.M.; Keri, R.S.; Hugar, M.H. Derivatives of benzimidazole pharmacophore: Synthesis, anticonvulsant, antidiabetic and DNA cleavage studies. Eur. J. Med. Chem., 2010, 45, 1753-1759.
[55]
Kumar, A.; D’Souza, S.S.; Nagaraj, S.R.M.; Gaonkar, S.L.; Salimath, B.P.; Rai, L.K.M. Anti-angiogenic and anti-proliferative effects of substituted-1,3,4-oxadiazole derivatives is mediated by down regulation of VEGF and inhibition of translocation of HIF-1in Ehrlich ascites tumor cells. Cancer Chemother. Pharmacol., 2009, 64, 1221-1233.
[56]
El-Din, G.M.M.; El-Gamal, M.I.; Abdel-Maksoud, M.S.; Hoyoo, K.; Oh, C.H. Synthesis and in vitro antiproliferative activity of new 1,3,4-oxadiazole derivatives possessing sulfonamide moiety. Eur. J. Med. Chem., 2015, 90, 45-52.
[57]
Jin, L.; Chen, J.; Song, B.; Chen, Z.; Yang, S.; Li, Q.; Hu, D.; Xu, R. Synthesis, structure and bioactivity of N′-substituted benzylidine-3,4,5-trimethoxy benzohydrazide and 3-acetyl-2-substituted phenyl-5 (3,4,5-trimethoxyphenyl)-2,3-dihydro-1,3,4-oxadiazole derivatives. Bioorg. Med. Chem. Lett., 2006, 16, 5036-5040.
[58]
Sing, P.; Sharma, P.K.; Sharma, J.K.; Upadhyay, A.; Kumar, N. Synthesis and evaluation of substituted diphenyl-1,3,4-oxadiazole derivatives for central nervous system depressant activit. Org. Med. Chem. Lett., 2012, 2, 8.
[59]
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-3b inhibitors with in vivo antidepressant activit. Bioorg. Chem., 2018, 77, 393-401.
[60]
Ergun, Y.; Orhan, F.O.; Ozer, U.G.; Gisi, G. Synergistic effect of [1H- [1,2,4] oxadiazole [4,3- a] quinoxalin-1-one] and antidepressant drug in the mouse forced swimming test: possible involvement of serotonergic pathway. Eur. J. Pharmacol., 2010, 630, 74-78.
[61]
Harfenist, M.; Heuser, D.J.; Joyner, C.T.; Batchelor, J.F.; White, H.L. Selective inhibitors of monoamine oxidase 3 Structure-activity relationship of tricyclics bearing imidazoline, oxadiazole, or tetrazole groups. J. Med. Chem., 1996, 39, 1857-1863.
[62]
Mayer, J.P.; Lewis, G.S.; McGee, C.; Bankaitis-Davis, D. Solid-phase synthesis of benzimidazoles. Tetrahedron Lett., 1998, 39, 6655-6658.
[63]
Shruthi, N.; Boja, P.; Vasantha, K.; Mumtaz, M.H.; Vaishali, M.R.; Vinitha, R.P.; Mahima, B.; Revannasiddppa, B.C. Novel benzimidazole-oxadiazole hybrid molecules as promising antimicrobial agents. RSC Adv., 2016, 6, 8303-8316.
[64]
Riss, T.L.; Moravec, R.A.; Niles, A.L.; Benink, H.A.; Worzella, T.J.; Minor, L. Cell viability assays. In:Sittampalam GS G-EN, Arkin, M.; Auld, D.; Austin, C.; Beejeek, B. editors.. Assay Guidance Manual; Bethesda (MD), USA: Eli Lilly & Co and National Centre for Advancing Translational Sciences.,, 2012.
[65]
Mohan, N.R.; Sreenivasa, S.; Manojkumar, K.E.; Rao, M.C.T.; Thippeswam, B.S.; Parameshwar, A. Suchetana. Synthesis, Antibacterial, anthelmintic and anti-inflammatory studies of novel methylpyrimidinesulfonyl piperazine derivatives. J. Braz. Chem. Soc., 2014, 25, 1012-1020.
[66]
Mohan, N.R.; Sreenivasa, S.; Manoj Kumar, K.E.; Anitha, H.C.; Rao, M.C.T.; Thippeswamy, B.S.; Gowda, V.K. Synthesis, characterization and in vitro antimicrobial study of series of 1-((substituted aryl/alkyl) sulfonyl)-4-tosylpiperazines. Indo. Am. J. Pharm., 2013, 3, 1513-1520.
[67]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feency, P.J. Adv. Drug Deliv. Rev., 1997, 23, 3.
[68]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feency, P.J. Adv. Drug Deliv. Rev., 2001, 46, 3.
[69]
QikProp, version 3.5; Schrödinger, LLC: New York, NY, 2014.
[70]
Bernard, D.; Zhao, Y.; Wang, S. AM-8553: A Novel MDM2 inhibitor with a promising outlook for potential clinical development. J. Med. Chem., 2012, 55, 4934-4935.
[71]
Protein Preparation Wizard; Epik version 2.3. 2012; Schrödinger, LLC, New York.
[72]
Jorgensen, W.L.; Maxwell, D.S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc., 1996, 118, 11225-11236.
[73]
LigPrep, version 3.1; Schrödinger, LLC: New York, NY, 2014.
[74]
Glide, version 3.3; Schrödinger, LLC: New York, NY, 2014.
[75]
Aguirre, G.M.; Bolani, H.; Cerecetto, A.; Gerpe, M.; Gonzalez, Y.F.; Sainz, A.; Denicola, C.O.; de Ocariz, J.J.; Nogal, D.J. Montero and A. Escario, Novel antiprotozoal products: Imidazole and mariana boiania, hugo cerecettoa, benzimidazole n-oxide derivatives and alejandra gerpea, related compounds. Arch. Pharm., 2004, 337, 259-270.
[76]
Vasantha, K.; Poojary, B.; Prathibha, A.; Shruthi, N. Synthesis of some novel 1,2-disubstituted benzimidazole-5-carboxylates via one-pot method using sodium dithionite and its effect on N-debenzylation. Synth. Commun., 2014, 44, 3414-3425.

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