INTERACTION OF PTERIDOPHYTIC BIOACTIVE COMPOUNDS WITH FUNGAL DIHYDROFOLATE REDUCTASE ENZYME AS INHIBITOR

Year 2023, , 1170 - 1176, 20.09.2023

Manohar Singh , Mansi Raghav , Akanksha Singh , Akanksha Kumari , Prıya Bansal , Surya Prakash , Abhıshek Kumar

https://doi.org/10.33483/jfpau.1270767

Abstract

Objective: Fungal infections which are relatively common mainly invades the body of an immunosuppressed patients and people undergoing therapy. These pathogens act through different pathways like the Dihydrofolate reductase (DHFR) has a role in the folate synthetic pathway which is responsible for DNA synthesis. Since the early ages herbal remedies were used and have been tested for treating these fungal infections. Previous studies have revealed the use of bioactive molecules of pteridophytes to demonstrate antifungal activity.
Material and Method: In the present study different pteridophytes were selected from available library which showed the presence of bioactive phytoconstituents. In-silico studies on DHFR target (PDB ID: 6DRS and PDB ID: 3QLW) was carried out using PyRx program (India) to determine the affinity of bioactive molecules against the fungal strain.
Result and Discussion: Molecular docking was performed with 11 bioactive molecules showing activity against the selected target proteins. So, we can conclude that the selected bioactive molecules are active against fungal strain and can be further investigated for both in-vivo and in-vitro studies.

Keywords

Dihydrofolate reductase (DHFR), fungal infection, molecular docking, pteridophytes

Supporting Institution

KIET SCHOOL OF PHARMACY, KIET GROUP OF INSTITUTIONS, DELHI-NCR, GHAZIABAD-201206, UTTAR PRADESH, INDIA

Project Number

NA

Thanks

Author acknowledges the KIET Group of Institutions, Ghaziabad, for the infrastructural support

PTERİDOPİTİK BİYOAKTİF BİLEŞİKLERİN İNHİBİTÖR OLARAK MANTAR DİHİDROFOLAT REDÜKTAZ ENZİMİ İLE ETKİLEŞİMİ

Abstract

Amaç: Nispeten yaygın olan mantar enfeksiyonları esas olarak immün sistemi baskılanmış hastaların ve tedavi gören kişilerin vücudunu istila eder. Bu patojenler, DNA sentezinden sorumlu olan folat sentezinde rol oynayan dihidrofolat redüktaz (DHFR) gibi farklı yolaklar üzerinden etki gösterir. İlk çağlardan beri bitkisel ilaçlara bu mantar enfeksiyonlarını tedavi etmek için kullanılmış ve test edilmiştir. Önceki çalışmalar, antifungal aktiviteyi göstermek için biyoaktif pteridofit moleküllerinin kullanıldığını ortaya koymaktadır.
Gereç ve Yöntem: Bu çalışmada, biyoaktif fito bileşenlerinin varlığını gösteren mevcut kütüphaneden farklı pteridofitler seçilmiştir. Biyoaktif moleküllerin mantar suşuna karşı afinitesini belirlemek için Pyrx (Hindistan) programı kullanılarak, DHFR hedefi (PDB ID 6DRS ve PDB ID 3QLW) üzerine in-siliko çalışmalar gerçekleştirilmiştir.
Sonuç ve Tartışma: Seçilen hedef proteinlere karşı aktivite gösteren 11 biyoaktif molekül ile molekler yerleştirme çalışması gerçekleştirilmiştir. Buna göre, seçilen biyoaktif moleküllerin mantar suşuna karşı aktif olduğu ve hem in-vivo hem de in vitro çalışmalar için daha fazla araştırılabileceği sonucuna varılmıştır.

Keywords

Dihidrofolat redüktaz (DHFR), mantar enfeksiyonu, moleküler yerleştirme, pteridofitler

Project Number

NA

References

• 1. Mujwar, S., Tripathi, A. (2022). Repurposing benzbromarone as antifolate to develop novel antifungal therapy for Candida albicans. Journal of Molecular Modelling, 28, 193. [CrossRef]
• 2. Hainer, B.L. (2003). Dermatophyte infections. American Family Physician, 67(1), 101-108.
• 3. Basak, T., Nath, V., Kumar, V., Goyal, A.K. (2021). In silico identification of antifungal compounds as mutant DHFRase inhibitors: structure-based approach, molecular dynamics simulation and structural integrity analysis. Journal of Computational Biophysics and Chemistry, 20(6), 589-602. [CrossRef]
• 4. Ghannoum, M.A., Rice, L.B. (1999). Antifungal agents: Mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clinical Microbiology Reviews, 12(4), 501-517. [CrossRef]
• 5. Chawla, P., Teli, G., Gill, R.K., Narang, R.K. (2021). An insight into synthetic strategies and recent developments of dihydrofolate reductase inhibitors. Chemistry Europe, 6(43), 12101-12145. [CrossRef]
• 6. DeJarnette, C., Luna-Tapia, A., Estredge, L.R., Palmer, G.E. (2020). Dihydrofolate reductase is a valid target for antifungal development in the human pathogen Candida albicans. mSphere, 5(3), e00374-20. [CrossRef] 7. Kaushik, K., Agarwal, S. (2019). The role of herbal antifungal agents for the management of fungal diseases: A systematic review. Asian journal of pharmaceutical and clinical research, 12(7), 34-40. [CrossRef]
• 8. Baskaran, X.R., Vigila, A.V.G., Zhang, S.Z., Feng, S.X., Liao, W.B. (2018). A review of the use of pteridophytes for treating human ailments. Journal of Zhejiang University-SCIENCE B, 19(2), 85-119.
• 9. Mimica-Dukic, N., Simin, N., Cvejic, J., Jovin, E., Orcic, D., Bozin, B. (2008). Phenolic compounds in field horsetail (Equisetum arvense L.) as natural antioxidants. Molecules, 13(7), 1455-1464.
• 10. Vastinge-Tuominen, M., Perera-Ivarsson, P., Shen, J., Bohlin, L., Rolfsen, W. (2004). The fern Polypodium decumanum, used in the treatment of psoriasis, and its fatty acid constituents as inhibitors of leukotriene b4 formation. Prostaglandins Leukotrienes and Essential Fatty Acids, 50(5), 279-284. [CrossRef]
• 11. Semwal, P., Painuli, S., Painuli, K.M., Antika, G., Tumer, T.B., Thapliyal, A., Setzer, W.N., Martorell, M., Alshehri, M.M., Taheri, Y., Daştan, S.D., Ayatollahi, S.A., Petkoska, A.T., Sharifi-Rad, J., Cho, W.C. (2021). Diplazium esculentum (Retz.) Sw.: Ethnomedicinal, phytochemical, and pharmacological overview of the himalayan ferns. Oxidative Medicine and Cellular Longevity, 2021, 1917890. [CrossRef]
• 12. Lin, L.J., Huang, X.B., Lv, Z.C. (2016). Isolation and identification of flavonoids components from pteris vittata l. SpringerPlus, 5(1), 1649. [CrossRef]
• 13. Chaturvedi, M., Kajal, N., Yadav, J.P. (2021). In silico approach for identification of natural compounds as potential COVID 19 main protease (Mpro) inhibitors. Virus Disease, 32, 325-329. [CrossRef]
• 14. Aliye, M., Dekebo, A., Tesso, H., Abdo, T., Eswaramoorthy, R., Melaku, Y. (2021). Molecular docking analysis and evaluation of the antibacterial and antioxidant activities of the constituents of Ocimum cufodontii. Scientific Reports, 11(1), 10101. [CrossRef]
• 15. Azam, S.S., Abbasi, S.W. (2013). Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines. Theoretical Biology and Medical Modelling, 10, 63. [CrossRef]
• 16. Ferreira, L.G., Dos Santos, R.N., Oliva, G., Andicopulo, A.D. (2015). Molecular docking and structure-based drug design strategies. Molecules, 20, 13384-13421. [CrossRef]
• 17. Susmi, T.F., Khan, M.R., Rahman, A., Mahmud, S., Saleh, A., Reza, A., Rahi, S. (2022). In vitro antioxidant and cytotoxicity activities and in silico anticancer property of methanolic leaf extract of Leucas indica. Informatics in Medicine Unlocked, 31, 100963. [CrossRef]
• 18. Pathak, R.K., Gupta, A., Shukla, R., Baunthiyal, M. (2018). Identification of new drug-like compounds from millets as Xanthine oxidoreductase inhibitors for treatment of Hyperuricemia: A molecular docking and simulation study. Computational Biology and Chemistry, 76, 32-41. [CrossRef]
• 19. James, J.P., Ail, P.D., Crasta, L., Kamath, R.S., Shura, M.H., Sindhu, T.J. (2023). In silico ADMET and molecular interaction profiles of phytochemicals from medicinal plants in Dakshina Kannada. Journal of Health and Allied Sciences NU (accepted). [CrossRef]
• 20. Article, O., Markandeyan, D., Kannaiyan, S., Suresh, S., Nimmakayala, R., Ilamurugan, R., Santhalingam, K., Paul, B. (2016). Virtual screening of phytochemicals for methotrexate like dihydrofolate reductase and aminoimidazole-4-carboxamide ribonucleotide (aicar) transformylase inhibitory property using molegro virtual docker. International Journal of Pharmacy and Pharmaceutical Sciences, 8(5), 83-87.