The Effect of 1,3,4-Oxadiazol and 1,2,4-Triazole Compounds on Urease and Pepsin Enzymes

Authors

  • Zahraa M. Abdnoor Department of Chemistry, College of sciences, Al-Nahrain University, Jadriya, Baghdad, Iraq
  • Nasreen R. Jber Department of Chemistry, College of sciences, Al-Nahrain University, Jadriya, Baghdad, Iraq
  • Aliaa Saadoon Abdul-Razaq Market Research and Consumer Protection Center University of Baghdad, Baghdad, Iraq

DOI:

https://doi.org/10.22401/smg3at04

Keywords:

Heterocyclic compounds , Helicobacter pylori , Inhibition enzymes , Pepsin enzyme , Thiadiazol

Abstract

The helicobacter pylori affected urease and pepsin enzymes in the stomach, so the object of this study is to screen the effect of bis 1,3,4-oxadiazole and bis 1,2,4, triazole derivatives compounds on h-pylori urease enzyme in vitro. The results show that urease was inhibited by all produced compounds when the concentration increased. The most effective urease inhibitor is determined to be the compounds (A3e, A3c, A3d and B3c). The clinical study involved studying the pepsin enzyme activity level in H-pylori patients and control, the results found that the activity of pepsin elevated in h-pylori patients as compared with control.  The prepared compounds were screened on pepsin enzyme in vitro and showed that all the prepared compounds decreased the pepsin activity as the concentration increased. The nitrogen heterocyclic compounds. This study concludes that nitrogen-containing heterocyclic compounds have an important future in the treatment of Helicobacter pylori disease.

References

Naushad, V.A.; Purayil, N.K.; Badi, A.; Chandra, P.; Abuzaid, H.O.; Abuhmaira, M.M. et al.; "Study the finding of helicobacter pylori antibodies in gastric and duodenal fluid in erosive gastritis and erosive duodenitis-a prospective study". Int. J. Acad. Med. Pharm., 5(3): 2381-2385, 2023.‏

Walsh, J.H.; Walter, L.P.; "The treatment of Helicobacter pylori infection in the management of peptic ulcer disease". N. Eng. J Med., 333 (15): 984-991.‏ 1995.

Kakooza, S.; "Prevalence and Factors associated with Helicobacter pylori among Adults between 18 and 40 Years at Butembe Health Centre III Kyankwanzi district". Uganda. SJHR-Africa, 2(6): 7-7, 2021.‏

Nintewoue, G.F.; Mabeku, L.P.; "Helicobacter Pylori Infection Promotes Gastric Premalignancies And Malignancies Lesions And Demotes Hyperplastic Polyps: A 5 Year Multicentric Study Among Cameroonian Dyspeptic Patients". Asian Pac. J. Cancer Prev. 24 (1): 171-183, 2023.

Kim, J.; Wang, T.; "Helicobacter pylori and gastric cancer". Gastro. End. Clin. North Am., 31(3): 451-465, 2021.

Shirani, M.; Pakzad, R.; Haddadi, M.H.; Akrami, S.; Asadi, A.; Kazemian, H. et al.; "The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis". BMC Infect. Dis., 23(1): 1-30, 2023.

Khanipour, E.; Bagherian, R.; Mohammadi, N.; Khoeiniha, M.H.; Saffari, F.; Parsarad, E. et al.; "Comparative Evaluation of Clinical, Endoscopic and Histopathological Findings of Helicobacter Pylori Associated Gastroduodenitis in Children". Int. J. Pediatr., 9(3): 13257-13268, 2021.

Johnson, K.S.; Yang, C.; Carter, J.E.; Worthington, A.K.; Robinson, E.K.; Lopez-Magaña, R. et al.; "Helicobacter pylori Chronic-Stage Inflammation Undergoes Fluctuations That Are Altered in tlpA Mutants". Infect Immun., 91(1): e00322-22,‏ 2023.

Su-Arcaro, C.; Liao, W.; Bieniek, K.; Constantino, M.A.; Decker, S.M.; Turner, B.S. et al.; "Unraveling the Intertwined Effect of pH on Helicobacter pylori Motility and the Microrheology of the Mucin-Based Medium It Swims in”. Microorganisms, 11(11): 2745, 2023.

Karaliute, I.; Ramonaite, R.; Bernatoniene, J.; Petrikaite, V.; Misiunas, A.; Denkovskiene, E. et al.; "Reduction of gastrointestinal tract colonization by Klebsiella quasipneumoniae using antimicrobial protein KvarIa". Gut Patho., 14 (1): 17, 2022.

Bhattamisra, S.K.; Yan, L; Lee, C.; Kuean, H.; Candasamy, M.; Liew Y. K. ; et al.; "Protective activity of geraniol against acetic acid and Helicobacter pylori-induced gastric ulcers in rats". J. Tradit. Complementary Med., 9 (3): 206-214, 2019.

Keogan, D.; "The Development of Metallohydroxamates as Novel Anti-Bacterial and Anti-Leishmanial Agents". [PhD Thesis], Dublin: Royal College of Surgeons in Ireland; 2018.

Li, M.; Ding, W.; Baruah, B.; Crans, D.; Wang, R.; "Inhibition of protein tyrosine phosphatase 1B and alkaline phosphatase by bis (maltolato) oxovanadium (IV)". J. Inorg. Biochem., 102 (10): 1846-1853 , 2008.‏

Karplus, P.A.; Matthew, A.P.; Robert, P.H.; "70 years of crystalline urease: what have we learned?". Acc. Chem. Res., 30 (8): 330-337, 1997.

Mobley, H.L.; Michael, D.I.; Robert, P.H.; "Molecular biology of microbial ureases", Microbiol. Rev., 59 (3): 451-480, 1995.‏

SarveAhrabi, Y.; "Anti-Helicobacter pylori Activity of New Derivatives of 1, 3, 4-Oxadiazole: In Silico Study". Avicenna J. Clin. Microbiol. Infect., 8(4): 135-138, 2021.‏

Siwach, A.; Prabhakar, K.; Verma; "Therapeutic potential of oxadiazole or furadiazole containing compounds". BMC chem., 14: 1-40,‏ 2020.

Lelyukh, M.I.; "Biological activity of heterocyclic systems based on functionally substituted 1, 3, 4-thia (oxa) diazoles (a review)". Farmatsevtychnyi zhurnal 6: 43-53, 2019.

Ghani, U.; Nisar, U.; "New potent inhibitors of tyrosinase: novel clues to binding of 1, 3, 4-thiadiazole-2 (3H)-thiones, 1, 3, 4-oxadiazole-2 (3H)-thiones, 4-amino-1, 2, 4-triazole-5 (4H)-thiones, and substituted hydrazides to the dicopper active site". Bioorg. Med. Chem., 18 (11): 4042-4048, 2010.

Hamoud, M. ; Osman, N.A.; Rezq, S.; Abd, El-Wahab, H.A.; Abdalla, E.A.; Abdel-Fattah, H. A. et al.; "Design and synthesis of novel 1, 3, 4-oxadiazole and 1, 2, 4-triazole derivatives as cyclooxygenase-2 inhibitors with anti-inflammatory and antioxidant activity in lps-stimulated RAW264. 7 macrophages". Bioorg. Chem., 124: 105808, 2022.

Kadambar, A.K.; Kalluraya, B.; Singh, S.; Agarwal, V.; Revanasiddappa, B.C.‏; "One‐pot three‐component azide‐alkyne cycloaddition: Synthesis of new pyrazole, 1, 2, 3‐triazole, and oxadiazole tethered and their anti‐inflammatory, quantitative structure‐activity relationship, and docking studies”. J. Heterocycl. Chem., 58 (2): 654-664, 2021.

Özdemir, A.; Sever, B.; Altıntop, M.D.; Temel, H.E.; Atlı, Ö.; Baysal, M. et al.; "Synthesis and evaluation of new oxadiazole, thiadiazole, and triazole derivatives as potential anticancer agents targeting MMP-9". Mol. 22 (7): 1109, 2017.

Thakkar, S.S.; Thakor, P.; Doshi, H.; Ray, A.; "1, 2, 4-Triazole and 1, 3, 4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities". Bioorg. Med. Chem., 25 (15): 4064-4075, 2017.

Hofny, H.A.; Mohamed, M.F.; Gomaa, H.A.; Abdel-Aziz, S.A.; Youssif, B.G.; El-Koussi, N.A.‏; "Design, synthesis, and antibacterial evaluation of new quinoline-1, 3, 4-oxadiazole and quinoline-1, 2, 4-triazole hybrids as potential inhibitors of DNA gyrase and topoisomerase IV". Bioorg. Chem., 112: 104920, 2021.

Archana, A.; "Synthesis of Novel Triazolyl / Oxadiazolyl / Thiadiazolyl-Piperazine as Potential Anticonvulsant Agents". Drug Res. 71 (4): 199-203., 2021.

Iqbal, A.K.; Khan, A.Y.; Kalashetti, M.B.; Belavagi, N.S.; Gong, Y.D.; Khazi, I.A.; "Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole / triazole / oxadiazole ring". Eur. J. Med. Chem., 53: 308-315, 2012.

Sravanthi, B.; Himavathi, G.; Suresh, M.; "Design, Synthesis of Novel Heterocyclics Bearing 1, 2, 4–Triazole, 1, 3, 4–Oxadiazole Conjugates as Potent Antibacterial and Antitubercular Agents a Computational Molecular Docking Techniques". Syn. of Nov. Heter. Bear., 1 (2,) 2022.

John, S.E.; Sharma, A.; Gulati, S.; Bora, D.; Shankaraiah,‏ N.; "Synthesis of cis-stilbene-based 1, 2, 4-triazole/1, 3, 4-oxadiazole conjugates as potential cytotoxic and tubulin polymerization inhibitors", New J Chem., 47(10): 4687-4697, 2023.

Bektas, H.; Albay, C.; Menteşe, E.; Sokmen, B.; Kurt, Z.; Şen; D.; "Synthesis, Antioxidant and Antiurease Activities of Some New 5, 6-dichloro-2-(4-fluorobenzyl)-1H-benzimidazole Derivatives Containing Furan, Oxadiazole, Triazole and Thiadiazole Moieties". Lett. Drug Des. Discov., 16 (8): 939-947, 2019.

Guda, D.R.; Park, S.J.; Lee, M.W.; Kim, T.J.; Lee, M.E.; "Syntheses and anti-allergic activity of 2-((bis (trimethylsilyl) methylthio / methylsulfonyl) methyl)-5-aryl-1, 3,4-oxadiazoles". Eur. J. Med. Chem., 62: 84-88, 2013.‏

Bitla, S.; Sagurthi, S.R.; Dhanavath, R.; Puchakayala, M.R.; Birudaraju, S.; Gayatri, A.A. et al.; "Design and synthesis of triazole conjugated novel 2, 5-diaryl substituted 1, 3, 4-oxadiazoles as potential antimicrobial and anti-fungal agents". J. Mol. Struct., 1220: 128705, 2020.

Weatherburn, M.W.; "Phenol-Hydrochloride Reaction for Determination of Ammonia". Anal. Biochem., 39(8): 971-4, 1967.

Muhammad, H.; Muhammad, S.; Muhammad, T.; Rama, N.H.; Zaib, S.; Aslam, M.A. et al.; "Synthesis, Urease Inhibition, Antioxidant And Antibacterial Studies of Some 4-Amino-5-Aryl-3H-1,2,4 Triazole3-Thiones And Their 3,6-Disubstituted 1,2,4-Triazolo[3,4-B]1,3,4 Thiadiazole Derivatives". J. Braz. Chem. Soc., 23(5): 854-860, 2012.

Murray, D.P.; "Guiide To Protein Purification Methods In Enzymologist". 2nd edition; Gulf Professional Publishing, California Institute of Technology Pasadena, California, USA, AP, V. 182, 1990.

Kaplan, N.O.; Sidney, P.C.; “Method Enzymology”, Eds., California institute of technology pasadena, california, USA, Vol. 10., 1955.‏

Sharma, R.; "Enzyme Inhibition and Bioapplications". Chapter1,Janeza Trdine 9,51000 Rijeka, Croatia, 2012.

Nguyen, S.P.; Do, T.C.; Tran, T.T.; Pham, T.K.; Tran, V.D.; Nguyen, K.T.; "Characteristics of basal gastric juice in Helicobacter pylori-associated gastritis before and after eradication therapy". Trop. J. Pharm. Res., 21 (10): 2241-2246, 2022.‏

Tsay, F.W.; Ping, I.H.; "H. pylori infection and extra-gastroduodenal diseases". J. Biomed. Res., 25: 1-8, 2018.

Alzahrani S.; Lina T. T.; Gonzalez J.; Pinchuk I. V.; Beswick E. J. and Reyes V. E.; "Effect of Helicobacter pylori on gastric epithelial cells". World J. Gastroenterol., 20 (36): 12767, 2014.‏

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Published

2024-03-15

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The Effect of 1,3,4-Oxadiazol and 1,2,4-Triazole Compounds on Urease and Pepsin Enzymes. ANJS 2024, 27 (1), 42-64. https://doi.org/10.22401/smg3at04.