Applied Chemical Engineering

Recent developments in catalytic and antimicrobial applications of benzimidazole Schiff base: A review

Sumit Kumar

Department of Chemistry, Gurukula Kangri University

Priyansh Kumar Utsuk

Department of Chemistry, Gurukula Kangri University

Ravinder Kumar

Department of Chemistry, Gurukula Kangri University

Prashant Tevatia

Department of Chemistry, Gurukula Kangri University

DOI: https://doi.org/10.59429/ace.v7i2.1860

Keywords: schiff base; benzimidazole; antibacterial activity; antifungal activity; antitumor and anticancer activity; antiviral activity

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Abstract

An amino acid and a carbonyl molecule are combined to generate Schiff bases complexes, which are useful compounds. Catalytic activity is high in many metals Schiff base complexes, especially chiral ones. Examples of processes include epoxidation, aldol condensation, hydroxylation, and oxidation. In several activities and in the presence of moisture, complexes display considerable catalytic activity. They have antibacterial, antifungal, antiviral, antimalarial, anticancer, and anti-HIV properties, among other biological activities. Research into these compounds’ coordination behavior has exploded because of specific metals on them, their biological activity and their intrinsic chemical interest as multidentate ligands. This article provides an overview of the numerous syntheses and uses for Schiff bases and their metal complexes.

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Author Biographies

Sumit Kumar, Department of Chemistry, Gurukula Kangri University

Research Scholar
Department of Chemistry
Gurukula Kangri (Deemed to be University)
Haridwar, Uttarakhand, India

Priyansh Kumar Utsuk, Department of Chemistry, Gurukula Kangri University

Research Scholar
Department of Chemistry
Gurukula Kangri (Deemed to be University)
Haridwar, Uttarakhand, India

Ravinder Kumar, Department of Chemistry, Gurukula Kangri University

Assistant Professor

Department of Chemistry
Gurukula Kangri (Deemed to be University)
Haridwar, Uttarakhand, India

Prashant Tevatia, Department of Chemistry, Gurukula Kangri University

Assistant Professor

Department of Chemistry
Gurukula Kangri (Deemed to be University)
Haridwar, Uttarakhand, India

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References

[1]. Genin MJ, Biles C, Keiser BJ, et. al. Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: Lead identification and sar of 3- and 4-substituted derivatives. Journal of Medicinal Chemistry 2000; 43(5): 1034–1040. doi: 10.1021/jm990383f.

[2]. Halay E, Acikbas Y. Click chemistry: A fascinating, Nobel-winning method for the improvement of biological activity. Applied Chemical Enginerring 2023; 6(1): 1–10.doi: 10.24294/ace.v6i1.1847.

[3]. Barker HA, Smyth RD, Weissbach H, et. al. Isolation and properties of crystalline cobamide coenzymes containing benzimidazole or 5, 6-dimethylbenzimidazole. Journal of Biological Chemistry 1960; 235(2): 480–488. doi: 10.1016/S0021-9258(18)69550-X.

[4]. Vigato PA, Tamburini S. The challenge of cyclic and acyclic schiff bases and related derivatives. Coordination Chemistry Reviews 2004; 248(17–20): 1717–2128.doi: 10.1016/j.cct.2003.09.003.

[5]. Supuran CT, Barboiu M, Luca C, et. al. Carbonic anhydrase activators. Part 14. Syntheses of mono and bis pyridinium salt derivatives of 2-amino-5-(2-aminoethyl)-and 2-amino-5-(3-aminopropyl)-1,3,4-thiadiazole and their interaction with isozyme II. European Journal of Medicinal Chemistry 1996; 31(7–8): 597–606.doi: 10.1016/0223-5234(96)89555-9.

[6]. Kraemer K, Semba RD, Eggersdorfer M, SchaumbergDA. Introduction: the diverse and essential biological functions of vitamins. Annals of nutrition & metabolism 2012; 61(3):185–191. doi: 10.1159/000343103.

[7]. O'Neil MJ, Smith A, Heckleman PE, et al. The Merck index: An encyclopedia of chemicals, drugs, and biologicals. Merck & Co.; 2001.

[8]. Salahuddin S, Shaharyar M, Mazumder A. Benzimidazoles: A biologically active compounds. Arabian Journal of Chemistry 2017; 10: S157–S173.doi: 10.1016/j.arabjc.2012.07.017.

[9]. Navarrete-Vázquez G, de Monserrat Rojano-Vilchis M, Yépez-Mulia L, et al. Synthesis and antiprotozoal activity of some 2-(trifluoromethyl)-1H-benzimidazole bioisosteres. European journal of medicinal chemistry 2006; 41(1):135–41.doi: 10.1016/j.ejmech.2005.09.001.

[10]. Phillips MA. CCCXVII.—The formation of 2-substituted benziminazoles. Journal of the Chemical Society (Resumed) 1928; 2393–2399. doi: 10.1039/JR9280002393.

[11]. Keri RS, Hiremathad A, Budagumpi S, Nagaraja BM. Comprehensive review in current developments of benzimidazole-based medicinal chemistry. Chemical Biology & Drug Design 2014; 86(1): 19–65.doi: 10.1111/cbdd.12462.

[12]. Cescon LA, Day AR. Preparation of some benzimidazolylamino acids. Reactions of amino acids with o-phenylenediamines. The Journal of Organic Chemistry 1962; 27(2): 581–586. doi: 10.1021/jo01049a056.

[13]. Alaqeel SI. Synthetic approaches to benzimidazoles from o-phenylenediamine: A literature review. Journal of Saudi Chemical Society. 2017; 21(2): 229–237.doi: 10.1016/j.jscs.2016.08.001.

[14]. Salahuddin, ShaharyarM, MazumderA, Ahsan MJ.Synthesis,characterizationandanticancer evaluationof2-(naphthalen-1-ylmethyl/naphthalen2-yloxymethyl)-1-[5-(substitutedphenyl)[1,3,4]oxadiazol-2-ylmethyl]-1H-benzimidazole.Arabian Journal of Chemistry. 2014; 7: 418-424.doi: 10.1016/j.arabjc.2013.02.001.

[15]. Ansari KF, Lal C. Synthesis, physicochemical properties, and antimicrobial activity of some new benzimidazole derivatives. European Journal of Medicinal Chemistry 2009; 44(10): 4028–4033.doi: 10.1016/j.ejmech.2009.04.037.

[16]. Ansari KF, Lal C, Parmar DL. Some novel oxadiazolyl/azetidinyl benzimidazole derivatives: Synthesis and in vitro biological evaluation. Synthetic Communications 2012; 42(24): 3553–3568. doi: 10.1080/00397911.2011.580881.

[17]. Bahrami K, Khodaei MM, Kavianinia I. A simple and efficient one-pot synthesis of 2-substituted benzimidazoles. Synthesis 2007; 2007(4): 547–550. doi: 10.1055/s-2007-965878.

[18]. Du LH, Wang YG. A rapid and efficient synthesis of benzimidazoles using hypervalent iodine as oxidant. Synthesis 2007; 2007(5): 675–678. doi: 10.1055/s-2007-965922.

[19]. Nale DB, Bhanage BM. N-substituted formamides as C1-sources for the synthesis of benzimidazole and benzothiazole derivatives by using zinc catalysts. Synlett 2015; 26(20): 2835–2842. doi: 10.1055/s-0035-1560319.

[20]. Tunçbilek M, Göker H, Ertan R, et. al. Synthesis and antimicrobial activity of some new anilino benzimidazoles. Archiv der Pharmazie 2006; 330(12): 372–376. doi: 10.1002/ardp.19973301203.

[21]. Layek S, Anuradha, Agrahari B, Pathak DD. Synthesis and characterization of a new Pd(II)-Schiff base complex [Pd (APD)2]: An efficient and recyclable catalyst for Heck-Mizoroki and Suzuki-Miyaura reactions. Journal of Organometallic Chemistry 2017; 846: 105–112. doi: 10.1016/j.jorganchem.2017.05.049.

[22]. Taggi AE, Hafez AM, Wack H, et. al. The development of the first catalyzed reaction of ketenes and imines: Catalytic, asymmetric synthesis of β-lactams. Journal of the American Chemical Society 2002; 124(23): 6626–6635. doi: 10.1021/ja0258226.

[23]. Kumar R, Kumar R, Mahiya K, Mathur P. Oxidation of substituted benzyl amines using a phenoxo-bridged dimeric nickel(II) complex: Synthesis, crystal structure and catalytic activity. Transition Metal Chemistry 2014; 40: 189–195. doi: 10.1007/s11243-014-9905-y.

[24]. Zhang H, Liao H, Li M. Synthesis and characterisation of Meso-Tetra (o-nitro) phenyltetraphenylporphyrin (IV). Applied Chemical Engineering 2018; 1(1): 25–34. doi: 10.24294/ace.v1i1.350.

[25]. Kumar A, Vashistha VK, Tevatia P, et al. Antimicrobial studies of tetraazamacrocyclic complexes of Fe (III) and Co(II). Der Pharma Chemica 2016; 8(1): 146–151.

[26]. Sweety, Kumar A, Tevatia P, Singh R. Antimicrobial and electrochemical studies of Schiff base of Mn(II) and Ni(II) tetraazamacrocyclic complexes. Journal of Chemical and Pharmaceutical Research 2016; 8(3): 444–448.

[27]. Kumar A, Vashistha VK, Tevatia P, Singh R.Electrochemical studies of DNA interaction and antimicrobial activities of MnII, FeIII, CoII and NiII Schiff base tetraazamacrocyclic complexes. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2017; 176: 123–133.doi: 10.1016/j.saa.2016.12.011.

[28]. Selvakumar B, Rajendiran V, Maheswari PU, et. al. Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage. Journal of inorganic biochemistry 2006; 100(3): 316–330. doi: 10.1016/j.jinorgbio.2005.11.018.

[29]. Pages BJ, Ang DL, Wright EP, Aldrich-WrightJR. Metal complex interactions with DNA. Dalton transactions 2015; 44(8): 3505–3526. doi: 10.1039/C4DT02700K.

[30]. Haas KL, Franz KJ. Application of metal coordination chemistry to explore and manipulate cell biology. Chemical Reviews 2009; 109(10): 4921–4960. doi: 10.1021/cr900134a.

[31]. Tušek-Božić L, Marotta E, Traldi P. Efficient solid-state microwave-promoted complexation of a mixed dioxa-diaza macrocycle with an alkali salt. Synthesis of a sodium ethyl 4-benzeneazophosphonate complex. Polyhedron 2007; 26(8): 1663–1668.doi: 10.1016/j.poly.2006.12.012.

[32]. Melson GA. Synthesis of macrocyclic complexes. In: Coordination Chemistry of Macrocyclic Compounds. Springer; 1979. pp. 17–144.

[33]. Lengacher R, Marlin A, Śmiłowicz D, BorosE. Medicinal inorganic chemistry—Challenges, opportunities and guidelines to develop the next generation of radioactive, photoactivated and active site inhibiting metal-based medicines. Chemical Society Reviews 2022; 51(18): 7715–7731. doi: 10.1039/D2CS00407K.

[34]. Szaciłowski K, Macyk W, Drzewiecka-Matuszek A, et al. Bioinorganic photochemistry: Frontiers and mechanisms. Chemical reviews 2005; 105(6): 2647–2694. doi: 10.1021/cr030707e.

[35]. Djilani A, Toudert N, Djilani S. Evaluation of the hypoglycemic effect and antioxidant activity of methanol extract of Ampelodesma mauritanica roots. Life Sciences and Medicine Research 2011; 31: 1–6.

[36]. Menteşe E, Yılmaz F, Emirik M, et al. Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors. Bioorganic Chemistry 2018; 76: 478–486.doi: 10.1016/j.bioorg.2017.12.023.

[37]. Kumar R, Mahiya K, Mathur P. Dimeric copper(II) complex of a new Schiff base ligand: Effect of morphology on the catalytic oxidation of aromatic alcohol. Dalton Transactions 2013; 42(24): 8553–8557.doi: 10.1039/C3DT50348H.

[38]. Zhang HZ, Gan LL, Wang H, et al. New progress in azole compounds as antimicrobial agents. Mini Reviews in Medicinal Chemistry 2017; 17(2): 122–166. doi: 10.2174/1389557516666160630120725.

[39]. Zha GF, Preetham HD, Rangappa S, et al. Benzimidazole analogues as efficient arsenals in war against methicillin-resistance staphylococcus aureus (MRSA) and its SAR studies. Bioorganic Chemistry 2021; 115: 105175.doi: 10.1016/j.bioorg.2021.105175.

[40]. Keri RS, Adimule V, Kendrekar P, Sasidhar BS. The nano-based catalyst for the synthesis of benzimidazoles. Topics in Catalysis 2022; 1–21. doi: 10.1007/s11244-022-01562-0.

[41]. Akande AA, Salar U, Khan KM, et al. Substituted benzimidazole analogues as potential α-amylase inhibitors and radical scavengers. ACS Omega 2021; 6(35): 22726–22739. doi: 10.1021/acsomega.1c03056.

[42]. Digwal CS, Yadav U, Sakla AP, et al. VOSO4 catalyzed highly efficient synthesis of benzimidazoles, benzothiazoles, and quinoxalines. Tetrahedron Letters 2016; 57(36): 4012–4016.doi: 10.1016/j.tetlet.2016.06.074.

[43]. Elged AH, Shaban SM, Eluskkary MM, et al. Impact of hydrophobic tails of new phospho-zwitterionic surfactants on the structure, catalytic, and biological activities of AgNPs. Journal of Industrial and Engineering Chemistry 2021; 94: 435–447.doi: 10.1016/j.jiec.2020.11.017.

[44]. Shaban SM, Aiad I, Yassin FA, Mosalam A. The tail effect of some prepared cationic surfactants on silver nanoparticle preparation and their surface, thermodynamic parameters, and antimicrobial activity. Journal of Surfactants and Detergents 2019; 22(6): 1445–1460. doi: 10.1002/jsde.12318.

[45]. Aiad I, El-Sukkary MM, El-Deeb A, et al. Surface properties, thermodynamic aspects and antimicrobial activity of some novel iminium surfactants. Journal of Surfactants and Detergents 2012; 15(3): 359–366.doi: 10.1007/s11743-011-1317-9.

[46]. Abd-ElHamid A, El-dougdoug W, Syam SM, et al. Synthesis of gemini cationic surfactants-based pyridine Schiff base for steel corrosion and sulfate reducing bacteria mitigation. Journal of Molecular Liquids 2023; 369: 120890.doi: 10.1016/j.molliq.2022.120890.

[47]. Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: A scientific statement from the American Heart Association. Circulation 2021; 143(21): e984–e1010. doi: 10.1161/CIR.0000000000000973.

[48]. Jeyakkumar P, Liu HB, Gopala L, et al. Novel benzimidazolyl tetrahydroprotoberberines: Design, synthesis, antimicrobial evaluation and multi-targeting exploration. Bioorganic & Medicinal Chemistry Letters 2017; 27(8): 1737–1743.doi: 10.1016/j.bmcl.2017.02.071.

[49]. Kumar R, Mathur P. Aerobic oxidation of 1,10-phenanthroline to phen-dione catalyzed by copper(ii) complexes of a benzimidazolyl Schiff base. RSC advances 2014; 4(63): 33190-33193. doi: 10.1039/C4RA03651D.

[50]. Kumar R, Mahiya K, Mathur P. Synthesis, spectral and structural characterization of Cu(II) complexes of a tridentate NNO donor Schiff base carrying a pendant benzimidazolyl arm. Indian Journal of Chemistry 2011; 50A: 775–780.

[51]. Alvarez LX, Christ ML, Sorokin AB. Selective oxidation of alkenes and alkynes catalyzed by copper complexes. Applied Catalysis A: General 2007; 325(2): 303–308.doi: 10.1016/j.apcata.2007.02.045.

[52]. Khattar R, Yadav A, Mahiya K, Mathur P. Nickel(II) complex based on bis-(1-(pyridin-2-yl-methyl)-benzimidazol-2-yl-methyl) ether and its utilization in the oxidation of 2-amino-4-tert-butylphenol. Indian Journal of Chemistry-Section A (IJCA) 2017; 56A(1): 36–42.

[53]. Ansari RM, Bhat BR. Schiff base transition metal complexes for Suzuki–Miyaura cross-coupling reaction. Journal of Chemical Sciences 2017; 129(9): 1483–1490. doi: 10.1007/s12039-017-1347-6.

[54]. Maurya MR, Sikarwar S, Joseph T, et al. Synthesis, characterization and catalytic potentials of polymer anchored copper(II), oxovanadium(IV) and dioxomolybdenum(VI) complexes of 2-(α-hydroxymethyl) benzimidazole. Reactive and Functional Polymers 2005; 63(1): 71–83.doi: 10.1016/j.reactfunctpolym.2005.02.008.

[55]. Kore R, Srivastava R. Synthesis and applications of novel imidazole and benzimidazole based sulfonic acid group functionalized Brönsted acidic ionic liquid catalysts. Journal of Molecular Catalysis A: Chemical 2011; 345(1–2): 117–126.doi: 10.1016/j.molcata.2011.06.003.

[56]. Yılmaz Ü, Küçükbay H, Şireci N, et al. Synthesis, microwave-promoted catalytic activity in Suzuki-Miyaura cross-coupling reactions and antimicrobial properties of novel benzimidazole salts bearing trimethylsilyl group. Applied Organometallic Chemistry 2011; 25(5): 366–373.doi: 10.1002/aoc.1772.

[57]. Said NR, Mustakim MA, Sani NNM, BaharinSNA. Heck reaction using palladium-benzimidazole catalyst: Synthesis, characterisation and catalytic activity. InIOP Conference Series: Materials Science and Engineering 2018; 458(1): 012019. doi: 10.1088/1757-899X/458/1/012019.

[58]. Ajani OO, Aderohunmu DV, Olorunshola SJ, et al. Facile synthesis, characterization and antimicrobial activity of 2-alkanamino benzimidazole derivatives. Oriental Journal of Chemistry 2016; 32(1): 109–120. doi: 10.13005/ojc/320111.

[59]. Mahmoud WH, Deghadi RG, Mohamed GG. Novel Schiff base ligand and its metal complexes with some transition elements. Synthesis, spectroscopic, thermal analysis, antimicrobial and in vitro anticancer activity. Applied Organometallic Chemistry 2016; 30(4): 221–230. doi: 10.1002/aoc.3420.

[60]. Ahmed N, Riaz M, Ahmed A, BhagatM. Synthesis, characterisation, and biological evaluation of Zn(II) complex with tridentate (NNO Donor) Schiff base ligand. International Journal of Inorganic Chemistry 2015; 2015: 607178. doi: 10.1155/2015/607178.

[61]. Mavrova AT, Yancheva D, Anastassova N, et al. Synthesis, electronic properties, antioxidant and antibacterial activity of some new benzimidazoles. Bioorganic & Medicinal Chemistry 2015; 23(19): 6317–6326.doi: 10.1016/j.bmc.2015.08.029.

[62]. Mohapatra RK, Das PK, El-ajaily MM, et al. Synthesis, spectral, thermal, kinetic and antibacterial studies of transition metal complexes with benzimidazolyl-2-hydrazones of o-hydroxyacetophenone, o-hydroxybenzophenone and o-vanillin. Bulletin of the Chemical Society of Ethiopia 2018; 32(3): 437–450.doi: 10.4314/bcse.v32i3.3.

[63]. Mohapatra RK, Mishra UK, Mishra SK, et al. Synthesis and characterization of transition metal complexes with benzimidazolyl-2-hydrazones of o-anisaldehyde and furfural. Journal of the Korean Chemical Society 2011; 55(6): 926–931.doi: 10.5012/jkcs.2011.55.6.926.

[64]. Göker H, Özden S, Yıldız S, BoykinDW. Synthesis and potent antibacterial activity against MRSA of some novel 1,2-disubstituted-1H-benzimidazole-N-alkylated-5-carboxamidines. European journal of medicinal chemistry 2005; 40(10): 1062–1069. doi: 10.1016/j.ejmech.2005.05.002.

[65]. Gao WW, Rasheed S, Tangadanchu V, et al. Design, synthesis and biological evaluation of amino organophosphorus imidazoles as a new type of potential antimicrobial agents. Science China Chemistry 2017; 60(6): 769–785.doi: 10.1007/s11426-016-9009-6.

[66]. Mahmood K, Hashmi W, Ismail H, et al. Synthesis, DNA binding and antibacterial activity of metal(II) complexes of a benzimidazole Schiff base. Polyhedron 2019; 157: 326–334.doi: 10.1016/j.poly.2018.10.020.

[67]. Alterhoni, E, Tavman A, Hacioglu M, et al. Synthesis, structural characterization and antimicrobial activity of Schiff bases and benzimidazole derivatives and their complexes with CoCl2, PdCl2, CuCl2 and ZnCl2. Journal of Molecular Structure 2021; 1229: 129498.doi: 10.1016/j.molstruc.2020.129498.

[68]. Sunitha M, Jogi P, Ushaiah B, Kumari CG. Synthesis, characterization and antimicrobial activity of transition metal complexes of Schiff base ligand derived from 3-ethoxy salicylaldehyde and 2-(2-Aminophenyl) 1-H-benzimidazole. E-Journal of Chemistry 2012; 9(4): 2516–2523. doi: 10.1155/2012/287909.

[69]. Keller P, Müller C, Engelhardt I, et al. An antifungal benzimidazole derivative inhibits ergosterol biosynthesis and reveals novel sterols. Antimicrobial Agents and Chemotherapy 2015; 59(10): 6296–6307.doi: 10.1128/aac.00640-15.

[70]. Mohapatra RK, Dash M, Mishra UK, et al. Synthesis, spectral characterization, and fungicidal activity of transition metal complexes with benzimidazolyl-2-hydrazones of glyoxal, diacetyl, and Benzil. Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry 2014; 44(5): 642–648. doi: 10.1080/15533174.2013.776592.

[71]. Shi L, Ge HM, Tan SH, et al. Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde. European journal of medicinal chemistry 2007;42(4):558-64.doi: 10.1016/j.ejmech.2006.11.010.

[72]. Fonkui TY, Ikhile MI, Njobeh PB, Ndinteh DT. Benzimidazole Schiff base derivatives: Synthesis, characterization and antimicrobial activity. BMC Chemistry 2019; 13(1): 127.doi: 10.1186/s13065-019-0642-3.

[73]. Bai YB, Zhang AL, Tang JJ, GaoJM. Synthesis and antifungal activity of 2-chloromethyl-1H-benzimidazole derivatives against phytopathogenic fungi in vitro. Journal of Agricultural and Food Chemistry 2013; 61(11): 2789–2795.doi: 10.1021/jf3053934.

[74]. Chandrika NT, Shrestha SK, Ngo HX, Garneau-TsodikovaS. Synthesis and investigation of novel benzimidazole derivatives as antifungal agents. Bioorganic & Medicinal Chemistry 2016; 24(16): 3680–3686.doi: 10.1016/j.bmc.2016.06.010.

[75]. Vashistha VK, Kumar A, Tevatia P, Kumar Das D. Synthesis, characterization, electrochemical and antimicrobial studies of iron(II) and nickel(II) macrocyclic complexes. Russian Journal of Electrochemistry 2021; 57(4): 348–356. doi: 10.1134/S1023193521040091.

[76]. Sweety, Vashistha VK, Kumar A, Singh R. Synthesis, electrochemical and antimicrobial studies of Me6-dibenzotetraazamacrocyclic complexes of Ni(II) and Cu(II) metal ions. Russian Journal of Electrochemistry 2019; 55(3): 161–167. doi: 10.1134/S1023193519020113.

[77]. Mishra L, Singh VK. Synthesis, structural and antifungal studies of Co (II), Ni (II), Cu (II) and Zn (II) complexes with new Schiff bases bearing benzimidazoles.Indian Journal Of chemistry 1993;32A(05): 446-449.

[78]. Mohamed GG, Ibrahim NA, Attia HAE. Synthesis and anti-fungicidal activity of some transition metal complexes with benzimidazole dithiocarbamate ligand. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2009; 72(3): 610–615.doi: 10.1016/j.saa.2008.10.051.

[79]. Alterhoni E, Tavman A, Hacioglu M, et al. Synthesis, characterization, electrochemical properties and antimicrobial activity of Schiff bases and benzimidazoles including ferrocene group and their CoCl2 complexes. Jordan Journal of Chemistry 2022; 17(1): 35–45. doi: 10.47014/17.1.4.

[80]. Yadav G, Ganguly S, Murugesan S, Dev A. Synthesis, anti-HIV, antimicrobial evaluation and structure activity relationship studies of some novel benzimidazole derivatives. Anti-infective agents 2015; 13(1): 65–77. doi: 10.2174/2211352512666141021002621.

[81]. Tonelli M, Vazzana I, Tasso B, et al. Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives. Bioorganic & Medicinal Chemistry 2009; 17(13): 4425–4440.doi: 10.1016/j.bmc.2009.05.020.

[82]. Vausselin T, Séron K, Lavie M, et al. Identification of a new benzimidazole derivative as an antiviral against hepatitis C virus. Journal of Virology 2016; 90(19): 8422–8434. doi: 10.1128/jvi.00404-16.

[83]. Tonelli M, Paglietti G, Boido V, et al. Antiviral activity of benzimidazole derivatives. I. Antiviral activity of 1-substituted-2-[(benzotriazol-1/2-yl) methyl] benzimidazoles. Chemistry & Biodiversity 2008; 5(11): 2386–2401.doi: 10.1002/cbdv.200890203.

[84]. Hwu JR, Singha R, Hong SC, et al. Synthesis of new benzimidazole-coumarin conjugates as anti-hepatitis C virus agents. Antiviral Research 2008; 77(2): 157–162.doi: 10.1016/j.antiviral.2007.09.003.

[85]. Xu YB, Yang L, Wang GF, et al. Benzimidazole derivative, BM601, a novel inhibitor of hepatitis B virus and HBsAg secretion. Antiviral research 2014; 107: 6–15.doi: 10.1016/j.antiviral.2014.04.002.

[86]. Brishty SR, Hossain MJ, Khandaker MU, et al. A comprehensive account on recent progress in pharmacological activities of benzimidazole derivatives. Frontiers in Pharmacology 2021; 12: 762807. doi: 10.3389/fphar.2021.762807.

[87]. Tonelli M, Simone M, Tasso B, et al. Antiviral activity of benzimidazole derivatives. II. Antiviral activity of 2-phenylbenzimidazole derivatives. Bioorganic & Medicinal Chemistry 2010; 18(8): 2937–2953.doi: 10.1016/j.bmc.2010.02.037.

[88]. Mahmood K, Akhter Z, Asghar MA, et al. Synthesis, characterization and biological evaluation of novel benzimidazole derivatives. Journal of Biomolecular Structure and Dynamics 2019; 38(6): 1670–1682. doi: 10.1080/07391102.2019.1617783.

[89]. Al-Masoudi NA, Aziz NM, Mohammed AT. Synthesis and In vitro anti-HIV activity of some new Schiff base ligands derived from 5-Amino-4-phenyl-4H-1,2,4-triazole-3-thiol and their metal complexes. Phosphorus, Sulfur, and Silicon and the Related Elements 2009; 184(11): 2891–2901. doi: 10.1080/10426500802591630.

[90]. Malik MA, Dar OA, Gull P, et al. Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy. MedChemComm 2018; 9(3): 409–436.doi: 10.1039/c7md00526a.

[91]. Sarkar P, Sutradhar S, Ghosh BN. Application in Pharmacological Field. Schiff Base Metal Complexes: Synthesis and Applications. 2023:129–47.doi: 10.1002/9783527839476.ch14.

[92]. El-Shekeil A, Obeid AO, Al-Aghbari S. Anticancer activity studies of some cyclic benzimidazole derivatives. European Journal of Chemistry 2012; 3(3): 356–358. doi: 10.5155/eurjchem.3.3.356-358.621.

[93]. Cheong JE, Zaffagni M, Chung I, et al. Synthesis and anticancer activity of novel water soluble benzimidazole carbamates. European Journal of Medicinal Chemistry 2018; 144: 372–385.doi: 10.1016/j.ejmech.2017.11.037.

[94]. Darwish SAZ, Elbayaa RY, Ashour HMA, et al. Potential anticancer agents: Design, synthesis of new pyrido [1,2-a] benzimidazoles and related derivatives linked to alkylating fragments. Medicinal Chemistry (Los Angeles) 2018; 8: 86–95. doi: 10.4172/2161-0444.1000498.

[95]. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 2018; 68(6): 394–424. doi: 10.3322/caac.21492.

[96]. Singal AG, Yopp AC, Gupta S, et al. Failure rates in the hepatocellular carcinoma surveillance process HCC surveillance failure rates. Cancer Prevention Research 2012; 5(9): 1124–1130. doi: 10.1158/1940-6207.CAPR-12-0046.

[97]. Dai X, Wang L, Deivasigamni A, et al. A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma. Oncotarget 2017; 8(8): 12831–12842.doi: 10.18632/oncotarget.14606.

[98]. Paul K, Sharma A, Luxami V. Synthesis and in vitro antitumor evaluation of primary amine substituted quinazoline linked benzimidazole. Bioorganic & Medicinal Chemistry Letters 2014; 24(2): 624–629.doi: 10.1016/j.bmcl.2013.12.005.

[99]. Noolvi MN, Patel HM, Singh N, et al. Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo [2,1-b] [1,3,4]-thiadiazole derivatives. European Journal of Medicinal Chemistry 2011; 46(9): 4411–4418.doi: 10.1016/j.ejmech.2011.07.012.

[100]. Magd-El-Din AA, Mousa HA, Labib AA, et al. Benzimidazole–Schiff bases and their complexes: Synthesis, anticancer activity and molecular modeling as Aurora kinase inhibitor. Zeitschrift für Naturforschung C 2018; 73(11–12): 465–478. doi: 10.1515/znc-2018-0010.

[101]. Galal SA, Hegab KH, Kassab AS, et al. New transition metal ion complexes with benzimidazole-5-carboxylic acid hydrazides with antitumor activity. European journal of medicinal chemistry 2009; 44(4): 1500–1508.doi: 10.1016/j.ejmech.2008.07.013.

[102]. Üstün E, Özgür A, Coşkun KA, et al. CO-releasing properties and anticancer activities of manganese complexes with imidazole/benzimidazole ligands. Journal of Coordination Chemistry 2016; 69(22): 3384–3394. doi: 10.1080/00958972.2016.1231921.

[103]. Kamil A, Akhter S, Ahmed M, et al. Antimalarial and insecticidal activities of newly synthesized derivatives of Benzimidazole. Pakistan Journal of Pharmaceutical Sciences2015; 28(6): 2179–2184.

[104]. Romero JA, Acosta ME, Gamboa ND, et al. Synthesis, antimalarial, antiproliferative, and apoptotic activities of benzimidazole-5-carboxamide derivatives. Medicinal Chemistry Research 2019; 28(1): 13–27.doi: 10.1007/s00044-018-2258-x.

[105]. Ndakala AJ, Gessner RK, Gitari PW, et al. Antimalarial Pyrido [1,2-a] benzimidazoles. Journal of Medicinal Chemistry 2011; 54(13): 4581–4589. doi: 10.1021/jm200227r.

[106]. Kanwal A, Ahmad M, Aslam S, et al. Recent advances in antiviral benzimidazole derivatives: A mini review. Pharmaceutical Chemistry Journal 2019; 53(3): 179–187. doi: 10.1007/s11094-019-01976-3.

[107]. Zawawi NKNA, Taha M, Ahmat N, et al. Synthesis, molecular docking studies of hybrid benzimidazole as α-glucosidase inhibitor. Bioorganic Chemistry 2017; 70: 184–191.doi: 10.1016/j.bioorg.2016.12.009.

[108]. Taha M, Mosaddik A, Rahim F, et al. Synthesis, antiglycation and antioxidant potentials of benzimidazole derivatives. Journal of King Saud University-Science 2020; 32(1): 191–194.doi: 10.1016/j.jksus.2018.04.003.

[109]. Khan KM, Ambreen N, Taha M, et al. Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors. Journal of Computer-aided Molecular Design 2014; 28(5): 577–585. doi: 10.1007/s10822-014-9745-z.

[110]. Taha M, Ismail NH, Imran S, et al. Synthesis of benzimidazole derivatives as potent β-glucuronidase inhibitors. Bioorganic Chemistry 2015; 61: 36–44.doi: 10.1016/j.bioorg.2015.05.010.

[111]. Özil M, Emirik M, Beldüz A, ÜlkerS. Molecular docking studies and synthesis of novel bisbenzimidazole derivatives as inhibitors of α-glucosidase. Bioorganic & Medicinal Chemistry 2016; 24(21): 5103–5114.doi: 10.1016/j.bmc.2016.08.024.

[112]. Menteşe E, Bektaş H, Ülker S, et al. Microwave-assisted synthesis of new benzimidazole derivatives with lipase inhibition activity. Journal of Enzyme Inhibition and Medicinal Chemistry 2014; 29(1): 64–68.doi: 10.3109/14756366.2012.753880.

[113]. Menteşe E, Emirik M, Sökmen BB. Design, molecular docking and synthesis of novel 5,6-dichloro-2-methyl-1H-benzimidazole derivatives as potential urease enzyme inhibitors. Bioorganic Chemistry 2019; 86: 151–158. doi: 10.1016/j.bioorg.2019.01.061.

[114]. Zengin A, Serbest K, Emirik M, et al. Binuclear Cu(II), Ni(II) and Zn(II) complexes of hydrazone Schiff bases: Synthesis, spectroscopy, DFT calculations, and SOD mimetic activity. Journal of Molecular Structure 2023; 1278: 134926.doi: 10.1016/j.molstruc.2023.134926.