The Antifungal Potential of Monoterpen and Monoterpenoids: Bioinformatics- Supported Trend Analysis

Öz

Aim: From the past to the present, plant compounds ranging from annual plants to perennial trees have been frequently preferred for disease treatment, either directly or indirectly. Plant secondary metabolites are also used for this purpose in the treatment of various fungal infections in plants, animals, and humans. The current study aims to reveal the frequency of antifungal effects of monoterpenoid compounds found in terpenes, one of the three main groups of plant secondary metabolites, in research conducted over the past 20 years. Materials and Methods: Data on studies investigating the antifungal effects of 20 different monoterpenoid compounds known to be obtained from a wide variety of plant groups in the literature were obtained from the PubMed database using the rentrez package in the R programming language. The data were subjected to normality tests and correlation matrices using the same programming language. Results: When the title “monoterpenoids” was provided together with the keyword “antifungal,” it was determined to be at the highest level of research. The highest average annual number of studies was determined to be 111.90±50.76 for thymol. The lowest annual number of articles was determined for the compound fenchol (0.24±0.43). The annual numbers of articles for 11 of the 20 compounds showed a normal distribution, and positive correlations were detected using correlation matrices for compounds that had been subject to a high number of studies. Conclusion: It was determined that the number of studies evaluated under the antifungal subheading of thymol, carvacrol, menthol, linalool, camphor, and menthol compounds was relatively higher than others. The fact that these compounds, which also have historical significance, are included in intensive antifungal effect studies is predictable, while the evaluation of monoterpenoids in the antibacterial and antimicrobial subheadings with a similar trend analysis may complement the data obtained from the current study.

Anahtar Kelimeler

• Antifungal activity
• plant secondary metabolites
• monoterpenoids
• R programming language
• rentrez

Monoterpen ve Monoterpenoidlerin Antifungal Karakterlerinin Belirlenmesinde Biyoinformatik Destekli Trend Analizi

Öz

Amaç: Geçmişten günümüze tek yıllık bitkilerden çok yıllık ağaçlara kadar çok geniş bir ölçekte bitkisel bileşikler doğrudan veya dolaylı olarak hastalık tedavisinde sıklıkla tercih edilmiştir. Bitki, hayvan ve insanlarda çeşitli fungal enfeksiyonların tedavisinde de bitkisel sekonder metabolitler bu amaç doğrultusunda kullanılmaktadır. Mevcut çalışma, üç temel bitkisel sekonder metabolit grubundan terpenlerde yer alan monoterpenoid bileşiklerinin antifungal etkilerinin son 20 yıldaki araştırmalardaki sıklığının ortaya koyulmasını amaçlamaktadır. Gereç ve Yöntem: Literatürde çok çeşitli bitki gruplarından elde edilebildiği bilinen 20 farklı monoterpenoid bileşiğinin antifungal etkilerine dair araştırmalara dair veriler R programlama dili aracılığıyla rentrez paketi kullanılarak pubmed veritabanından çekilmiştir. Çekilen veriler yine aynı programlama dili ile normal dağılım testleri ve korelasyon matrislerine tabi tutulmuştur. Bulgular: Monoterpenoidler üst başlığı “antifungal” anahtar kelimesi ile birlikte verildiğinde en yüksek araştırma seviyesinde olduğu belirlendi. Yıllık ortalama en yüksek araştırma sayısı 111,90±50,76 ile thymol olduğu belirlendi. En düşük yıllık makale sayısı ise fenchol (0,24±0,43) bileşiği için belirlendi. 20 bileşenden 11 tanesine ait makalelerin yıllık sayılarının normal dağılım gösterdiği, yüksek sayıda araştırmaya tabi olmuş bileşikler için korelasyon matrisleri ile pozitif korelasyon tespit edildi. Sonuç: Thymol, carvacrol, menthol, linalool, camphor ve menthol bileşiklerine ait antifungal alt başlığından derğlendirilen araştırmaların sayısının diğerlerine göre göreceli olarak daha fazla olduğu belirlendi. Tarihsel öneme de sahip bu bileşiklerin yoğun antifungal etki araştırmalarında yer bulmaları tahmin edilebilir bir durumu ifade ederken, monoterpenoidlerin benzer bir trend analizi ile antibakteriyel ve antimikrobiyal alt başlıklarında da değerlendirilmesi mevcut çalışmadan elde edilen verileri tamamlayıcı nitelikte olabilir.

Anahtar Kelimeler

• Antifungal aktivite
• bitkisel sekonder metabolitler
• monoterpenoidler
• R programlama dili
• rentrez

Kaynakça

1. 1] Reichling, J. (2010). Plant-microbe interactions and secondary metabolites with antibacterial, antifungal and antiviral properties. Annual plant reviews volume 39: Functions and biotechnology of plant secondary metabolites, 39, 214-347.
2. [2] Coleman, J. J., Ghosh, S., Okoli, I., & Mylonakis, E. (2011). Antifungal activity of microbial secondary metabolites. PloS one, 6(9), e25321.
3. [3] Ruparelia, J., Rabari, A., Mitra, D., Panneerselvam, P., Das- Mohapatra, P. K., & Jha, C. K. (2022). Efficient applications of bacterial secondary metabolites for management of biotic stress in plants. Plant Stress, 6, 100125.
4. [4] Ribera, A. E., & Zuñiga, G. (2012). Induced plant secondary metabolites for phytopatogenic fungi control: a review. Journal of soil science and plant nutrition, 12(4), 893-911.
5. [5] Pusztahelyi, T., Holb, I. J., & Pócsi, I. (2015). Secondary metabolites in fungus-plant interactions. Frontiers in plant science, 6, 573.
6. [6] Tiwari, R., & Rana, C. S. (2015). Plant secondary metabolites: a review. International Journal of Engineering Research and General Science, 3(5), 661-670.
7. [7] Tiring, G., Satar, S., & Özkaya, O. (2021). Sekonder metabolitler. Bursa Uludağ Üniversitesi Ziraat Fakültesi Dergisi, 35(1), 203-215.
8. [8] Alaca, F., & Arslan, N. (2012). Sekonder metabolitlerin bitkiler açısından önemi. Ziraat Mühendisliği, (358), 48-55.

9. [9] Pereira, F. D. O., Mendes, J. M., Lima, I. O., Mota, K. S., Oliveira, W. A., & Lima, E. D. O. (2015). Antifungal activity of geraniol and citronellol, two monoterpenes alcohols, against Trichophyton rubrum involves inhibition of ergosterol biosynthesis. Pharmaceutical Biology, 53(2), 228–234. https:// doi.org/10.3109/13880209.2014.913299
10. [10] Gazdağlı, A., Sefer, Ö., Yörük, E., Varol, G. I., Teker, T., & Albayrak, G. (2018). Investigation of camphor effects on Fusarium graminearum and F. culmorum at different molecular levels. Pathogens, 7(4), 90.
11. [11] Singh, S., Fatima, Z., Ahmad, K., & Hameed, S. (2018). Fungicidal action of geraniol against Candida albicans is potentiated by abrogated CaCdr1p drug efflux and fluconazole synergism. PLOS ONE, 13(8), e0203079.
12. [12] Shaban, M., Al-Dhaheri, R. S., Al-Shaer, M., & Al- Marzouqi, A. H. (2020). Carvacrol modulates the expression and activity of antioxidant enzymes in Candida auris. Journal of Medical Microbiology, 69(5), 697–705.
13. [13] Scariot, F. J., Foresti, L., Delamare, A. P. L., & Echeverrigaray, A. S. (2020). Activity of monoterpenoids on the in vitro growth of two Colletotrichum species and the mode of action on C. acutatum. Pesticide Biochemistry and Physiology, 170, 104698.
14. [14] Salehi, B., Mishra, A. P., Shukla, I., Sharifi‐Rad, M., Contreras, M. D. M., Segura‐Carretero, A., & Sharifi‐Rad, J. (2018). Thymol, thyme, and other plant sources: Health and potential uses. Phytotherapy research, 32(9), 1688-1706.
15. [15] Marchese, A., Orhan, I. E., Daglia, M., Barbieri, R., Di Lorenzo, A., Nabavi, S. F., & Nabavi, S. M. (2016). Antibacterial and antifungal activities of thymol: A brief review of the literature. Food chemistry, 210, 402-414.
16. [16] Jyoti, Dheer, D., Singh, D., Kumar, G., Karnatak, M., Chandra, S., & Shankar, R. (2019). Thymol chemistry: A medicinal toolbox. Current Bioactive Compounds, 15(5), 454- 474.
17. [17] Can Baser, K. H. (2008). Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Current pharmaceutical design, 14(29), 3106-3119.
18. [18] Herman, A., Tambor, K., & Herman, A. (2016). Linalool affects the antimicrobial efficacy of essential oils. Current microbiology, 72(2), 165-172.
19. [19] Memar, M. Y., Raei, P., Alizadeh, N., Aghdam, M. A., & Kafil, H. S. (2017). Carvacrol and thymol: strong antimicrobial agents against resistant isolates. Reviews and Research in Medical Microbiology, 28(2), 63-68.
20. [20] dos Santos, É. R., Maia, J. G. S., Fontes-Júnior, E. A., & do Socorro Ferraz Maia, C. (2022). Linalool as a therapeutic and medicinal tool in depression treatment: a review. Current Neuropharmacology, 20(6), 1073-1092.
21. [21] Matasyoh, J. C., Kiplimo, J. J., Karubiu, N. M., & Hailstorks, T. P. (2007). Chemical composition and antimicrobial activity of essential oil of Tarchonanthus camphoratus. Food chemistry, 101(3), 1183-1187.
22. [22] İşcan, G. (2017). Antibacterial and Anticandidal Activities of Common Essential Oil Constituents. Records of Natural Products, 11(4).
23. [23] Alves, M. F., Blank, A. F., Gagliardi, P. R., Arrigoni-Blank, M. de F., Nizio, D. A. de C., Brito, F. de A. & Sampaio, T. S. (2018). Essential oils of Myrcia lundiana Kiaersk and their major compounds show differentiated activities against three phytopathogenic fungi. Bioscience Journal, 34(5), 1200–1209
24. [24] Mathur, A., Meena, A., & Luqman, S. (2024). Monoterpenoids: An upcoming class of therapeutic agents for modulating cancer metastasis. Phytotherapy research, 38(2), 939-969