Evaluation of Antibacterial and Anticandidal Activities of Some Imidazole, Benzimidazole and Benztriazole Derivatives

Document Type : Original Article

Authors

1 Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

2 Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

In recent years, resistance to conventional antimicrobial drugs has become a serious concern in the clinic. Hence, the discovery of novel and effective antimicrobial agents with improved properties is of great value. In this study, the antibacterial and anticandidal activities of some imidazole, benzimidazole and benztriazole derivatives (C1-C8) against several species of Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Salmonella typhi as well as one species of fungi including Candida albicans, were evaluated using Clinical & Laboratory Standards Institute (CLSI) method. Antimicrobial evaluation revealed that among the tested compounds, imidazole derivative (C5) indicated the highest activity against bacterial strains and Candida albicans. It was found that compound C5 is more potent than ampicillin against S. aureus strain (MIC =2-16 µg/mL) and possessed excellent anticandidal activity (MIC =1 µg/mL) which was comparable to Amphotericin B as the positive control. In addition, cytotoxic activity of the tested compounds was investigated using MTT assay. The results of MTT assay demonstrated that the toxicity of the tested compounds was less than 35%.  
Please cite this article as: Sara Sadeghian, Ahmad Gholami, Soghra Khabnadideh, Razieh Razmi, Issa Sadeghain, Younes Ghasemi & Zahra Rezaei. Evaluation of Antibacterial and Anticandidal Activities of Some Imidazole, Benzimidazole and Benztriazole Derivatives. Trends in Pharmaceutical Sciences. 2022;8(2):75-84  .doi: 10.30476/TIPS.2022.93637.1126

Keywords


1.    Siddiqui AM, Sattigeri JA, Javed K, Shafi S, Shamim M, Singhal S, Malik ZM. Design, synthesis and biological evaluation of spiropyrimidinetriones oxazolidinone derivatives as antibacterial agents. Bioorg Med Chem Lett. 2018. 28(7): 1198-1206.
2.    Guo Y, Xu T, Bao C, Liu Z, Fan J, Yang R, Qin S. Design and synthesis of new norfloxacin-1, 3, 4-oxadiazole hybrids as antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). Eur J Pharm Sci. 2019 Aug 1;136:104966. doi: 10.1016/j.ejps.2019.104966. Epub 2019 Jun 21.
3.    Altıntop MD, Atlı Ö, Ilgın S. Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents. Eur J Med Chem. 2016;108:406-14.
4.    Altıntop MD, Özdemir A, Turan-Zitouni G, Ilgın S, Atlı Ö. Synthesis and biological evaluation of some hydrazone derivatives as new anticandidal and anticancer agents. Eur J Med Chem.  2012 Dec;58:299-307.
5.    Wani MY, Ahmad A, Aqlan FM, Al-Bogami AS. Azole based acetohydrazide derivatives of cinnamaldehyde target and kill Candida albicans by causing cellular apoptosis. ACS Med Chem Lett. 2020 Feb 5;11(4):566-574.
6.    Khalilullah H, Khan S, Nomani MdS, Ahmed B. Synthesis, characterization and antimicrobial activity of benzodioxane ring containing 1, 3, 4-oxadiazole derivatives. Arab J Chem. 2016;9: S1029-S1035.
7.    Sadeghpour H, Khabnadideh S, Zomorodian K, Pakshir K, Hoseinpour K, Javid N, Faghih-Mirzaei E, Rezaei Z. Design, synthesis, and biological activity of new triazole and nitro-triazole derivatives as antifungal agents. Molecules. 2017 Jul 10;22(7):1150.
8.    Osmaniye D, Cavusoglu BK, Saglik BN, Levent S, Cevik UA, Alti O, Ozkay Y, Kaplancikli ZA. Synthesis and anticandidal activity of new imidazole-chalcones. Molecules. 2018 Apr 4;23(4):831. doi: 10.3390/molecules23040831.
9.    Castillo KF, Bello-Vieda NJ, Nunez-Dallos NG, Pastrana HF, Celis AM, Restrepo S, Hurtado JJ, Avila AG. Metal complex derivatives of azole: A study on their synthesis, characterization, and antibacterial and antifungal activities. J Braz Chem Soc. 2016;27(12):2334-47.doi: 10.5935/0103-5053.20160130
10.    Doğan İS, Sarac S, Sari S, Kart D, Gokhan SE, Vural I, Dalkara S. New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies. Eur J Med Chem. 2017 Apr 21;130:124-138.
11.    Rezaei Z, Khabnadideh S, Pakshir K, Hossaini Z, Amiri F, Assadpour E. Design, synthesis, and antifungal activity of triazole and benzotriazole derivatives. Eur J Med Chem. 2009 Jul;44(7):3064-7. doi: 10.1016/j.ejmech.2008.07.012. Epub 2008 Jul 19.
12.    Shaikh, IN, Hosamani KM, Kurjogi MM. Design, synthesis, and evaluation of new α‐aminonitrile‐based benzimidazole biomolecules as potent antimicrobial and antitubercular agents. Arch Pharm (Weinheim). 2018 Feb;351(2). doi: 10.1002/ardp.201700205. Epub 2018 Jan 22.
13.    Stingaci E, Zveaghinteva M, Pogrebnoi S, Lupascu L, Valica V, Uncu L, et al. New vinyl-1, 2, 4-triazole derivatives as antimicrobial agents: Synthesis, biological evaluation and molecular docking studies. Bioorg Med Chem Lett. 2020 Sep 1;30(17):127368. doi: 10.1016/j.bmcl.2020.127368. Epub 2020 Jun 26.
14.    Thakare  PP, Shinde AD, Chavan AP, Nyayanit NV, Bobade VD, Mhaske PC. Synthesis and Biological Evaluation of New 1, 2, 3‐Triazolyl‐Pyrazolyl‐Quinoline Derivatives as Potential Antimicrobial Agents. ChemistrySelect. 2020. 5(15): 4722-4727.
15.    Tangadanchu VKR, Sui YF, Zhou CH. Isatin-derived azoles as new potential antimicrobial agents: Design, synthesis and biological evaluation. Bioorg Med Chem Lett. 2021. 41: 128030.
16.    Rezaei Z, Khabnadideh S, Zomorodian K, Pakshir K, Kashi G, Sanagoei N, Gholami S. Design, synthesis and antifungal activity of some new imidazole and triazole derivatives. Arch Pharm (Weinheim). 2011 Oct;344(10):658-65. doi: 10.1002/ardp.201000357. Epub 2011 Aug 25.
17.    Franklin R, Cockerill WM, Alder J, Dudley MN, Eliopoulos GM, Ferraro MJ, Hardy DJ, Hecht DW, Hindler JA, Patel JB, Powell M. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard ninth edition. Clinical and Laboratory Standards Institute. 2012; 12: 1-88.
18.    Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996 Feb;14(1):33-8,27-8. doi: 10.1016/0263-7855(96)00018-5.
19.    Nishant kumar S, Jubi J, Nisha GV, Asha A, Dileep C, Dileep kumar BS. Investigation of antifungal activity of stilbenes alone and in combination with fluconazole against candida albicans. Int J Pharm Pharm Sci. 2014;6(4):304-7.
20.    Zamani L, Khabnadideh S, Zomorodian K, Sakhteman A, Gholami A, Rezaei Z, et al. Docking, Synthesis, Antifungal and Cytotoxic Activities of Some Novel Substituted 4H-Benzoxazin-3-one. Polycycl Aromat Compd. 2021;41:2, 347-367. doi: 10.1080/10406638.2019.1584575.
21.    Kathiravan MK, Salake AB, Chothe AS, Dudhe PB, Watode RP, et al. The biology and chemistry of antifungal agents: a review. Bioorg Med Chem. 2012 Oct 1;20(19):5678-98. doi: 10.1016/j.bmc.2012.04.045. Epub 2012 May 9.
22.    Bouchal B, Abrigach F, Takfaoui A, Errahhali ME, Errahhali ME, Dixneuf PH, et al. Identification of novel antifungal agents: antimicrobial evaluation, SAR, ADME–Tox and molecular docking studies of a series of imidazole derivatives. BMC Chem.  2019 Aug 6;13(1):100. doi: 10.1186/s13065-019-0623-6. eCollection 2019 Dec.
23.    Jagadale S, Chavan A, Shinde A, Sisode V, Bobade VD, Mhaske PC. Synthesis and antimicrobial evaluation of new thiazolyl-1, 2, 3-triazolyl-alcohol derivatives. Med Chem Res. 2020. 29(6): 989-999.
24.    Sui YF, Li D, Wang J, Yadav Bheemanaboina RR, Ansari MF, Gan LL, Zhou CH. Design and biological evaluation of a novel type of potential multi-targeting antimicrobial sulfanilamide hybrids in combination of pyrimidine and azoles. Bioorg Med Chem Lett. 2020 Mar 15;30(6):126982. doi: 10.1016/j.bmcl.2020.126982. Epub 2020 Jan 20.
25.    Sapijanskaitė-Banevič B, Palskys V, Vaickelionienė R, Šiugždaitė J, Kavaliauskas P, Grybaitė B. Synthesis and Antibacterial Activity of New Azole, Diazole and Triazole Derivatives Based on p-Aminobenzoic Acid. Molecules. 2021 Apr 29;26(9):2597. doi: 10.3390/molecules26092597.
26.    Imran M, Bawadekji A, Alotaibi N. Synthesis and evaluation of antimicrobial properties of some azole derivatives. Trop J Pharm Res. 2020. 19(2):377-382. doi: 10.4314/tjpr.v19i2.21.
27.    Sari S, Kart D, Ozturk N, Kaynak FB, Gencel M, Taskor G, Karakurt A, Sarac S, Essiz Sebnem Dalkara S. Discovery of new azoles with potent activity against Candida spp. and Candida albicans biofilms through virtual screening. Eur J Med Chem. 2019 Oct 1;179:634-648. doi: 10.1016/j.ejmech.2019.06.083. Epub 2019 Jun 29.