Synthesis and Evaluation of 4-[5-((4-hydroxybenzylidene) amino)-1,3,4-thiadiazol-2-yl] Phenol Compound Biological Activities

M. Saeed, Ban; A.N. Al-Jadaan, Shaker; A. Abbas, Basil

doi:10.30699/ijmm.19.1.29

year 19, Issue 1 (January - February 2025) Iran J Med Microbiol 2025, 19(1): 29-39 | Back to browse issues page

‎ 10.30699/ijmm.19.1.29

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M. Saeed B, A.N. Al-Jadaan S, A. Abbas B. Synthesis and Evaluation of 4-[5-((4-hydroxybenzylidene) amino)-1,3,4-thiadiazol-2-yl] Phenol Compound Biological Activities. Iran J Med Microbiol 2025; 19 (1) :29-39
URL: http://ijmm.ir/article-1-2559-en.html

Synthesis and Evaluation of 4-[5-((4-hydroxybenzylidene) amino)-1,3,4-thiadiazol-2-yl] Phenol Compound Biological Activities

Ban M. Saeed¹

, Shaker A.N. Al-Jadaan²

, Basil A. Abbas³

1- Department of Microbiology, Al-Zahraa College of Medicine, University of Basrah, Basrah, Iraq
2- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Basrah, Basrah, Iraq
3- Microbiology Department, College of Veterinary Medicine, University of Basrah, Basrah, Iraq , basil.abbas@uobasrah.edu.iq

Abstract: (467 Views)

Background and Aim: The 1,3,4-thiadiazole molecule has a heterocyclic structure in several medications and natural products. It is an essential part of several pharmacological classes, such as antibacterial, anti-inflammatory, analgesic, antiviral, antineoplastic, and anti-tubercular drugs. Thiadiazole compounds have attracted interest in the field of medicinal chemistry because of their biological and pharmacological activities, especially their anticancer capacities. This study aimed to synthesize a new phenol compound with antibacterial and anticancer efficacy. The relationship between Schiff-base and antibacterial and antitumor actions was studied.
Materials and Methods: The microwave approach was employed to create the novel compound known as 4-[5-((4-hydroxybenzylidene) amino)-1,3,4-thiadiazol-2-yl] phenol. Its composition was validated by analyzing several elements, including FT-IR, 1H-NMR, and ¹³C-NMR. The biological activity of Gram-positive and Gram-negative bacteria was examined using four different bacterial isolates. This was observed through the plate-hole diffusion method. The anticancer efficacy of the compound was evaluated against prostate cancer cells.
Results: The synthesized phenol compound demonstrated enhanced anticancer activity against prostate cancer cells in vitro but no effect on normal cells. Its minimum inhibitory concentration (MIC) for Klebsiella pneumoniae and Bacillus cereus was 1 mg/ml, while it was determined 3 and 5 mg/ml for Staphylococcus aureus and Escherichia coli, respectively.
Conclusion: The synthesized compound showed favorable antibacterial and anticancer activities. It offers potential for subsequent research on a new Schiff-base with higher efficiency, lower toxicity, and higher selectivity in these activities.

Keywords: Antibacterial, Anticancer, MIC, Prostate Cancer Cell, Schiff-base

Full-Text [PDF 1075 kb] (67 Downloads) | | Full-Text (HTML) (33 Views)

Type of Study: Original Research Article | Subject: Antimicrobial Substances
Received: 2025/01/9 | Accepted: 2025/03/1 | ePublished: 2025/03/30

References

1. Anthwal T, Paliwal S, Nain S. Diverse Biological Activities of 1,3,4-Thiadiazole Scaffold. Chem. 2022;4(4):1654-71. [DOI:10.3390/chemistry4040107]

2. Radha VP, Kirubavathy SJ, Chitra S. Synthesis, characterization and biological investigations of novel Schiff base ligands containing imidazoline moiety and their Co(II) and Cu(II) complexes. J Mol Struct. 2018;1165:246-58. [DOI:10.1016/j.molstruc.2018.03.109]

3. Mushtaq I, Ahmad M, Saleem M, Ahmed A. Pharmaceutical signifcance of Schif bases: an overview. Fut J Pharm Sci. 2024;10:16. [DOI:10.1186/s43094-024-00594-5]

4. Abu-Dief AM, Abdel-Rahman LH, Abdelhamid AA, Marzouk AA, Shehata MR, Bakheet MA, et al. Synthesis and characterization of new Cr (III), Fe (III) and Cu (II) complexes incorporating multi-substituted aryl imidazole ligand: Structural, DFT, DNA binding, and biological implications. Spectrochim Acta A: Mol Biomol Spectrosc. 2020;228:117700. [DOI:10.1016/j.saa.2019.117700] [PMID]

5. Al-Azawi K, AL-Duhaidahawi DL, Al-Amiery A, Kadhum AAH. Synthesis of Schiff base metal complexes with motivating scavenging potential studies. Free Rad Antioxi. 2019;9(1):01-04. [DOI:10.5530/fra.2019.1.1]

6. Ceramella J, Iacopetta D, Catalano A, Cirillo F, Lappano R, Stefania Sinicrop M. A review on the antimicrobial activity of schiff bases: data collection and recent studies. Antibiotics. 2022;11(2):191. [DOI:10.3390/antibiotics11020191] [PMID] [PMCID]

7. Chaudhary NK, Guragain B, Chaudhary SK, Mishra P. Schiff base metal complex as a potential therapeutic drug in medical science: A critical review. BIBECHANA. 2021;18(1):214-30. [DOI:10.3126/bibechana.v18i1.29841]

8. Sinicropi MS, Jessica Ceramella J, Iacopetta D, Catalano A, Mariconda A, Rosano C, et al. Metal complexes with schiff bases: data collection and recent studies on biological activities. Int J Mol Sci. 2022;23:14840. [DOI:10.3390/ijms232314840] [PMID] [PMCID]

9. Basher NA, Flifel IA, Mashaf AA. Synthesis, characterization and antibacterial study of some complexes derivatives from1, 3, 4–Thiadiazole Schiff base. In 2nd International Scientific Conference of Al-Ayen University. IOP conference series: Materials Science and Engineering 2020 Sep 1 (Vol. 928, No. 5, p. 052009). IOP Publishing. [DOI:10.1088/1757-899X/928/5/052009]

10. Onyeyilim EL, Ezeokonkwo MA, Ugwu DI, Uzoewulu CP, Eze FU, Okonkwo VI, Eze CC and Ezugwu JA. Carbohydrazide analogues: a review of synthesis and biological activities. Mini-Rev Med Chem. 2022;22(4):661-82. [DOI:10.2174/1389557521666210831154935] [PMID]

11. Hassan AM, Said AO, Heakal BH, Younis A, Aboulthana WM, Mady MF. Green synthesis, characterization, antimicrobial and anticancer screening of new metal complexes incorporating Schiff base. ACS omega. 2022;7(36):32418-31. [DOI:10.1021/acsomega.2c03911] [PMID] [PMCID]

12. Ali A, Ali A, Tahir A, Bakht MA, Ahsan MJ. Ultrasound promoted green synthesis, anticancer evaluation, and molecular docking studies of hydrazines: a pilot trial. J. Enzyme Inhib. Med. Chem. 2022;37(1):135-44. [DOI:10.1080/14756366.2021.1995727] [PMID] [PMCID]

13. Hassan A, Heakal B, Khamis H, Hassan G, Marzouk E, Abdelmoaz M, et al. Design, Synthesis, DFT Studies and Anticancer Activity of Novel Metal Complexes Containing 1,3,5-triazino [1,2-a] benzimidazole Moiety Using Microwave as an Approach for Green Chemistry. Egypt J Chem. 2021;64(1):323-40. [DOI:10.21608/ejchem.2020.29618.2639]

14. Meera G, Rohit KP, Saranya S, Anilkumar G. Microwave assisted synthesis of five membered nitrogen heterocycles. Royal Soci Chem. 2020;(10):36031-41. [DOI:10.1039/D0RA05150K] [PMID] [PMCID]

15. Bhagat S, Sharma N, Chundawat TS. Synthesis of some salicylaldehyde‐based Schiff bases in aqueous media. J Chem. 2013;2013(1):909217. [DOI:10.1155/2013/909217]

16. Saeed BM, Al-Jadaan SA, Kushaish RA, Abbas BA. Antimicrobial activity, minimum inhibitory concentration and cytotoxicity of thiadiazol compound. Romanian J Infec Dis. 2024;27(1):22-7. [DOI:10.37897/RJID.2024.1.4]

17. Saeed BM, Abbas BA, Al-Jadaan SA. Molecular detection of tetracycline resistance genes in Bacillus cereus isolated from food sources. Basrah J Vet Res. 2018;17(3):223-34.

18. Hoa NT, Baccigalupi L, Huxham A, Smertenko A, Van PH, Ammendola S, et al. Characterization of Bacillus species used for oral bacteriotherapy and bacterioprophylaxis of gastrointestinal disorders. App Environ Microb. 2000;66(12):5241-7. [DOI:10.1128/AEM.66.12.5241-5247.2000] [PMID] [PMCID]

19. Saeed BM, Al-Jadaan SA, Abbas BA. Synthesis of a Novel 4, 4’-[1, 4-phenylenebis (1, 3, 4-thiadiazole-5, 2-diyl)] bis (azaneylylidene) bis (methaneylylidene) diphenol and Determination of Its pharmacological and antimicrobial Activities. In Journal of Physics: Conference Series 2019 Jul 1 (Vol. 1279, No. 1, p. 012037). IOP Publishing. [DOI:10.1088/1742-6596/1279/1/012037]

20. Bayram G, Nzeyimana A, Utku S, Ülger M, Aslan G, Berçin E. Study on synthesis and antimicrobial activities of some michael-type addition compounds. J Fac Pharm Ankara. 2012;45(2):182-93. [DOI:10.33483/jfpau.867768]

21. Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. J Pharm Anal. 2016;6(2):71-9. [DOI:10.1016/j.jpha.2015.11.005] [PMID] [PMCID]

22. Kowalska-Krochmal B and Dudek-Wicher R . The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance. Pathogene 2021;4;10(2):165. [DOI:10.3390/pathogens10020165] [PMID] [PMCID]

23. Saeed BM, Al-Jadaan SA, Abbas BA. Study on Anticancer Activity of 4, 4'-[1, 4-phenylenebis (1, 3, 4-thiadiazole-5, 2-diyl)] bis (azaneylylidene) bis (methaneylylidene) diphenolon Breast Cancer Cells. Arch Razi Institute. 2021;76(4):821-7. [DOI:10.22092/ARI.2021.355941.1742]

24. Al-Timimi LAN. Antibacterial and anticancer activities of fenugreek seed extract. Asian Pac J Cancer Prev. 2019;20(12):3771-6. [DOI:10.31557/APJCP.2019.20.12.3771] [PMID] [PMCID]

25. Camelia ES, George MN, Constantin D, Miron TC, Anamaria H , Octavian TO, et al. Synthesis of 1,3,4-Thiadiazole Derivatives and Their Anticancer Evaluation. Int J Mol Sci. 2023;14;24(24):17476. [DOI:10.3390/ijms242417476] [PMID] [PMCID]

26. Tsacheva I, Todorova Z, Momekova D, Momekov G, Koseva N. Pharmacological activities of schiff bases and their derivatives with low and high molecular phosphonates. Pharmaceuticals. 2023;16(7):938. [DOI:10.3390/ph16070938] [PMID] [PMCID]

27. Munawar KS, Haroon SM, Hussain SA, Raza H. Schiff bases: Multipurpose pharmacophores with extensive biological applications. J Basic Appl Sci. 2018;14:217-29. [DOI:10.6000/1927-5129.2018.14.34]

28. Iacopetta D, Lappano R, Mariconda A, Ceramella J, Sinicropi MS, Saturnino C, et al. Newly synthesized imino-derivatives analogues of resveratrol exert inhibitory effects in breast tumor cells. Int J Mol Sci. 2020;21(20):7797. [DOI:10.3390/ijms21207797] [PMID] [PMCID]

29. Afridi HH, Shoaib M, Al-Joufi FA, Shah SW, Hussain H, Ullah A, et al. Synthesis and investigation of the analgesic potential of enantiomerically pure schiff bases: a mechanistic approach. Molecules. 2022;27(16):5206. [DOI:10.3390/molecules27165206] [PMID] [PMCID]

30. Kaushik S, Paliwal SK, Iyer MR, Patil VM. Promising Schiff bases in antiviral drug design and discovery. Med Chem Res. 2023;32(6):1063-76. [DOI:10.1007/s00044-023-03068-0] [PMID] [PMCID]

31. Ceramella J, Iacopetta D, Catalano A, Cirillo F, Lappano R, Sinicropi MS. A review on the antimicrobial activity of Schiff bases: Data collection and recent studies. Antibiotics. 2022;11(2):191. [DOI:10.3390/antibiotics11020191] [PMID] [PMCID]

32. Al Zoubi W. Biological activities of schiff bases and their complexes: a review of recent works. Int J Org Chem. 2013;3(3):73-95. [DOI:10.4236/ijoc.2013.33A008]

33. Bharadwaj A, Rastogi A, Pandey S, Gupta S, Sohal JS. Multidrug‐resistant bacteria: their mechanism of action and prophylaxis. BioMed Res Int. 2022;2022(1):5419874. [DOI:10.1155/2022/5419874] [PMID] [PMCID]

34. Kumar S, Bansal H. A Review on Synthesis and Antimicrobial Activity of Schiff Bases. Int J Innov Sci Eng Technol. 2021;8(7):46-64. Available from: [https://ijiset.com/vol8/v8s7/IJISET_V8_I07_05.pdf]

35. Kakkassery JT, Raphael VP, Johnson R. In vitro antibacterial and in silico docking studies of two Schiff bases on Staphylococcus aureus and its target proteins. Fut J Pharm Sci. 2021;7(1):1-9. [DOI:10.1186/s43094-021-00225-3]

36. Alorini TA, Al-Hakimi AN, Saeed SE, Alhamzi EH, Albadri AE. Synthesis, characterization, and anticancer activity of some metal complexes with a new Schiff base ligand. Arab J Chem. 2022;15(2):103559. [DOI:10.1016/j.arabjc.2021.103559]

37. Hadjicharalambous A, Bournakas N, Newman H, Skynner MJ, Beswick P. Antimicrobial and cell-penetrating peptides: understanding penetration for the design of novel conjugate antibiotics. Antibiotics. 2022;11(11):1636. [DOI:10.3390/antibiotics11111636] [PMID] [PMCID]

38. Mushtaq I, Ahmad M, Saleem M, Ahmed A. Pharmaceutical significance of Schiff bases: An overview. Fut J Pharm Sci. 2024;10(1):16. [DOI:10.1186/s43094-024-00594-5]

39. Obradović R, Joksimović N, Janković N, Kosanić M, Matić J, Milović E, et al. Discovery of Schiff bases as potent antibacterial and antifungal agents. New J Chem. 2024;48(40):17492-9. [DOI:10.1039/D4NJ02683G]

40. Robinson GF, Sooda KK, Phillips RM, Allison SJ, Javid FA. Investigation of the cytotoxicity induced by didocosahexaenoin, an omega 3 derivative, in human prostate carcinoma cell lines. Curr Res Pharmacol Drug Discov. 2022;3:100085. [DOI:10.1016/j.crphar.2022.100085] [PMID] [PMCID]

41. Hemanth K, Lakshmanan K, Rajagopal K, Byran P, Byran G. A review on biological activities: 1,3,4- thiadiazole and its derivatives. Rasayan J Chem. 2022;15(2):1573-87. [DOI:10.31788/RJC.2022.1516443]