Synthesis, characterization, antimicrobial, antioxidant, and anti-cancer activity of new hybrid structures based on benzimidazole and thiadiazole
DOI:
https://doi.org/10.1590/Keywords:
Benzimidazole, Thiadiazole, Antimicrobial, Anti-cancer, AntioxidantAbstract
Hybrid structures containing multiple pharmacophore units with known activity have attracted attention due to their promising outcomes. In this study, several new hybrid structures containing benzimidazole and thiadiazole units were synthesized. The newly synthesized compounds were structurally analyzed using 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antimicrobial, in vitro anti-cancer, and antioxidant activities of all compounds were investigated. In vitro antimicrobial activities of the compounds were determined against Gram-positive (S. aureus ATCC 29213, E. faecalis ATCC 29212), Gram-negative (E. coli ATCC 25922, P. aeruginosa ATCC 27853) bacteria and fungi (C. albicans ATCC 10231) by using broth microdilution method. The compound 5g bearing 4-methoxyphenyl derivative showed the best activity with 32 μg/mL against S. aureus ATCC 29213 and P. aeruginosa ATCC 27853. The MTT test was used to determine the cytotoxicity of the produced compounds on the MCF-7 (human breast cancer) and L-929 (fibroblast) cell lines. FRAP method was used to determine the antioxidant properties of synthesized compounds. The Ferric Reducing Antioxidant Power of the compounds 5a, 5b, and 5c showed more antioxidant properties than vitamin E. The compound 5g stands out in the series in that it is not toxic on the healthy cell line and has promising antimicrobial activity.
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Acar Çevik U, Kaya B, Celik I, Rudrapal M, Rakshit G, Karayel A, et al. New benzimidazole-triazole derivatives as topoisomerase I Inhibitors: Design, synthesis, anti-cancer screening, and molecular modeling studies. ACS omega. 2024; 9(11): 13359-13372.
Anastassova N, Georgieva I, Milanova V, Tzoneva R, Radev K, Yancheva D, et al. Synthesis of new triazole and thiadiazole derivatives of the n, n’-disubstituted benzimidazole-2-thione and evaluation of their antitumor potential. J Chem Technol Metall. 2022; 57(4): 709-717.
Ansari KF, Lal C. Synthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives. Eur J Med Chem. 2009; 44(10): 4028-4033.
Arora ROK, Kaur N, Bansal Y, Bansal G. Novel coumarin-benzimidazole derivatives as antioxidants and safer anti-inflammatory agents. Acta Pharm Sin B. 2014; 4(5): 368-375.
Aydemir N, Bilaloğlu R. Genotoxicity of two anti-cancer drugs, gemcitabine and topotecan, in mousebone marrow in vivo. Mutat Res Genet Toxicol Environ Mutagen. 2003; 537(1): 43-51.
Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996; 239(1): 70-76.
Celik I, Çevik UA, Karayel A, Işık A, Kayış U, Gül UD, et al. Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole-Thiadiazole Hybrids. ACS omega. 2022; 7(50): 47015-47030.
Çevik UA, Işık A, Evren A E, Kapusız Ö, Gül ÜD, Özkay Y, et al. Synthesis of new benzimidazole derivatives containing 1, 3, 4-thiadiazole: their in vitro antimicrobial, in silico molecular docking and molecular dynamic simulations studies. SAR QSAR Environ Res. 2022; 33(11): 899-914.
Debus H. Ueber die einwirkung des ammoniaks auf glyoxal. Justus Liebigs Ann Chem. 1858; 107(2): 199-208.
Hobrecker F. Reduction-products of nitracetamide compounds. Deut Chem Ges Ber. 1872; 5: 920-924.
Ismael GF, Rosa DD, Mano MS, Awada A. Novel cytotoxic drugs: old challenges, new solutions. Cancer Treat Rev. 2008; 34(1): 81-91.
Işık A, Çevik UA, Çelik I, Bostancı HE, Karayel A, Gündoğdu G, et al. Benzimidazole-hydrazone derivatives: Synthesis, in vitro anti-cancer, antimicrobial, antioxidant activities, in silico DFT and ADMET studies. J Mol Struct. 2022; 1270: 133946.
Işık A, Acar Çevik U, Karayel A, Ahmad I, Patel H, Çelik İ, Gul UD, Bayazıt G, Bostancı HE, Kocak A, Ozkay Y, Kaplancıklı ZA. Synthesis, DFT Calculations, In Silico Studies, and Antimicrobial Evaluation of Benzimidazole-Thiadiazole Derivatives. ACS Omega. 2024; 9(16); 18469-18479
Jahan J, Barik S, Chagaleti BK, Kathiravan MK, Deivasigamani P. The synthetic approach of benzimidazole derivatives as anti-inflammatory agents. Jmpas. 2023; 12(5): 6049-6058.
Karki SS, Panjamurthy K, Kumar S, Nambiar M, Ramareddy SA, Chiruvella KK, et al. Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4’-fluorophenyl)-imidazo [2, 1-b][1, 3, 4] thiadiazole derivatives as potent anticancer agents. Eur J Med Chem. 2011; 46(6): 2109-2116.
Keri RS, Hiremathad A, Budagumpi S, Nagaraja BM. Comprehensive review in current developments of benzimidazole-based medicinal chemistry. Chem Biol Drug Des. 2015; 86(1): 19-65.
Khadri MN, Begum AB, Sunil MK, Khanum SA. Synthesis, docking and biological evaluation of thiadiazole and oxadiazole derivatives as antimicrobial and antioxidant agents. Res Chem. 2020; 2: 100045.
Khokra SL, Choudhary D. Benzimidazole an important scaffold in drug discovery. Asian J Biochem Pharm Res. 2011; 3(1): 476-486.
Mohapatra TR, Ganguly S. Design, Synthesis, Antibacterial and Antitubercular Studies of Some New Benzimidazoles. A Combined Experimental and Computational Approach. ChemistrySelect. 2024; 9(12): e202304791.
Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001; 2(9): 533-543.
Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015; 109(7): 309-318.
Ranjith PK, Rajeesh P, Haridas KR, Susanta NK, Row TNG, Rishikesan R, et al. Design and synthesis of positional isomers of 5 and 6-bromo-1-[(phenyl) sulfonyl]-2-[(4-nitrophenoxy) methyl]-1H-benzimidazoles as possible antimicrobial and antitubercular agents. Bioorg Med Chem Lett. 2013; 23(18): 5228-5234.
Shi L, Ge HM, Tan SH, Li HQ, Song YC, Zhu HL, et al. Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde. Eur J Med Chem. 2007; 42(4): 558-564.
Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol. 1997; 82(2): 291-295.
Sridevi CH, Balaji K, Naidu A, Sudhakaran R. Synthesis of some phenylpyrazolo benzimidazolo quinoxaline derivatives as potent antihistaminic agents. J Chem. 2010; 7: 234-238.
Vasantha K, Basavarajaswamy G, Rai MV, Boja P, Pai VR, Shruthi N, et al. 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(7): 1420-1426.
Yadav S, Narasimhan B. Perspectives of benzimidazole derivatives as anticancer agents in the new era. Anti-Cancer Agents Med Chem. 2016; 16(11): 1403-1425.
Wayne, P. Clinical and L.S. Institute, Performance standards for antimicrobial susceptibility testing. Clinical and Laboratory Standards Institute. 2017.
Wayne P. Clinical and Laboratory Standards Institute: Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard. CLSI document M27-A3 and Supplement S. 2008; 3: 6-12.
Wright JB. The chemistry of the benzimidazoles. Chem Rev. 1951; 48(3): 397-541.
Xing F, Hu Q, Qin Y, Xu J, Zhang B, Yu X, et al. The relationship of redox with hallmarks of cancer: the importance of homeostasis and context. Front Oncol. 2022; 12: 862743.
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