Prangos aricakensis'ten izole edilen yeni olası antibakteriyel molekül, Daukosterol: Antibakteriyel aktivite ve DD-peptidaz ve giraz üzerinden moleküler yerleştirme yaklaşımları

Serbay Şafak Gökçimen; Yaşar İpek; Tevfik Ozen; İbrahim Demirtas; Lütfi Behçet

doi:10.18016/ksutarimdoga.vi.1683529

EN TR

A new possible antibacterial compound isolated from Prangos aricakensis, Daucosterol: Antibacterial activity and molecular docking approaches via DD-peptidase and gyrase

Abstract

Prangos species have been used for years to treat various ailments due to their chemical components. Eastern Türkiye is home to the locally endemic species Prangos aricakensis. This work is the first to isolate the daucosterol molecule from P. aricakensis stems. Daucosterol's structure was ascertained by 1D and 2D NMR analysis. Daucosterol has been studied to have many effects in many areas, such as antibacterial, immune system strengthening, and anti-cancer. Studies have been conducted on the molecule's antibacterial activity in vitro and its predicted molecular docking with antibiotic target proteins in silico. Compared to standard antibiotics, daucosterol had better effects against Bacillus cereus (512 μg/mL) and Listeria monocytogenes (1024 μg/mL). Additionally, daucosterol (512 μg/mL) and amoxicillin (512 μg/mL) demonstrated comparable efficacy against Enterococcus faecalis and Klebsiella pneumoniae. To predict the antibacterial effect of daucosterol in a computer environment, molecular docking interactions of daucosterol with DD-peptidase and gyrase (antibiotic target proteins) were studied and compared with tetracycline as a control antibiotic. Daucosterol and DD-peptidase showed perfect binding affinity, as -9.00, and daucosterol and gyrase had -8.90 kcal/mol. Results showed that the daucosterol molecule interacted with antibiotic target proteins and can be used as an in vitro antibacterial agent.

Keywords

Prangos aricakensis'ten izole edilen yeni olası antibakteriyel molekül, Daukosterol: Antibakteriyel aktivite ve DD-peptidaz ve giraz üzerinden moleküler yerleştirme yaklaşımları

Öz

Prangos türleri kimyasal bileşenlerinden dolayı yıllardır çeşitli rahatsızlıkların tedavisinde kullanılmıştır. Türkiye’nin doğusu, yerel olarak endemik tür olan Prangos aricakensis'e ev sahipliği yapmaktadır. Bu çalışma, daukosterol molekülünün P. aricakensis gövde kısmından izole edildiği ilk çalışmadır. Daukosterol'ün yapısı 1D ve 2D NMR analiziyle belirlenmiştir. Daukosterol’ün antibakteriyel, immün sistemi güçlendirici ve anti-kanser gibi birçok alanda etkisinin araştırıldığı bilinmektedir. Molekülün in vitro antibakteriyel aktivitesi ve in silico antibiyotik hedef proteinlerle öngörülen moleküler yerleşimi üzerine çalışmalar yürütülmüştür. Standart antibiyotiklerle karşılaştırıldığında, daukosterol Bacillus cereus'a (512 μg/mL) ve Listeria monocytogenes'e (1024 μg/mL) karşı iyi etkilere sahip çıkmıştır. Ayrıca, daukosterol (512 μg/mL) ve amoksisilin (512 μg/mL), Enterococcus faecalis ve Klebsiella pneumoniae'ye karşı karşılaştırılabilir etkinlik göstermiştir. Bilgisayar ortamında Daukosterol’ün antibakteriyel etkisini tahmin etmek için daukosterol’ün DD-peptidaz ve giraz (antibiyotik hedef proteinleri) ile moleküler yerleştirme etkileşimleri incelendi ve kontrol antibiyotik olarak tetrasiklinin bu hedef proteinlerle olan etkileşimleri ile karşılaştırıldı. Daukosterol ve DD-peptidaz -9.00 kcal/mol ile çok iyi bağlanma afinitesi gösterirken daukosterol ve giraz ise -8.90 kcal/mol ile iyi bir etkileşime sahip görünmektedir. Sonuçlar daukosterol molekülünün antibiyotik hedef proteinlerle etkileyici etkileşimlere sahip olduğunu ve in vitro antibakteriyel reaktif olarak kullanılabileceğini gösterdi.

Anahtar Kelimeler

Supporting Institution

TÜBİTAK

Project Number

221Z330

Ethical Statement

Gerek yoktur.

Thanks

Türkiye Bilimsel ve Teknolojik Araştırma Kurumunun çalışmalarımıza desteğine teşekkürler

References

Abdollahnezhad, H., Bahadori, M. B., Pourjafar, H., & Movahhedin, N. (2021). Purification, characterization, and antioxidant activity of daucosterol and stigmasterol from Prangos ferulacea. Lett. Appl. Biosci, 10, 2174-2180. https://doi.org/10.33263/lianbs102.21742180
Abdullah, S. A., Mohammed, M. J., Marah, S., & Ozen, T. (2024). Metal ion complexes of 2-thioxoimidazolidine-4-one derivatives mixed ligand synthesis, characterization, in-vitro biological activities and in-silico studies. Journal of the Indian Chemical Society, 101(10), 101344. https://doi.org/10.1016/ j.jics.2024.101344
Andrews, J. M. (2001). Determination of minimum inhibitory concentrations. Journal of antimicrobial Chemotherapy, 48(suppl_1), 5-16. https://doi.org/10.1093/jac/48.suppl_1.5
Bandow, J. E., Brötz, H., Leichert, L. I. O., Labischinski, H., & Hecker, M. (2003). Proteomic approach to understanding antibiotic action. Antimicrobial agents and chemotherapy, 47(3), 948-955. https://doi.org/10.1128/aac.47.3.948-955.2003
Behçet, L., Yapar, Y., & Olgun, Ş. (2019). Prangos aricakensis (Apiaceae), a new species from eastern Turkey. Phytotaxa, 401(1), 55-63. https://doi.org/10.11646/phytotaxa.401.1.5
Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N., & Bourne, P. E. (2000). The protein data bank. Nucleic acids research, 28(1), 235-242. https://doi.org/10.1107/ 97809553602060000722
BIOVIA, D. S. (2019). BIOVIA Discovery Studio Visualize 2019, version 2019. Dassault Systèmes BIOVIA: San Diego, CA, USA. https://doi.org/10.1016/b978-0-12-816954-4.00002-4
Bruno, M., Ilardi, V., Lupidi, G., Quassinti, L., Bramucci, M., Fiorini, D., Venditti, A., & Maggi, F. (2019). The nonvolatile and volatile metabolites of Prangos ferulacea and their biological properties. Planta medica, 85(11/12), 815-824. https://doi.org/10.1055/a-0873-8622

Cho, E. J., Choi, J. Y., Lee, K. H., & Lee, S. (2012). Isolation of antibacterial compounds from Parasenecio pseudotaimingasa. Horticulture, Environment, and Biotechnology, 53, 561-564. https://doi.org/10.1007/s13580-012-0040-4
Delnavazi, M.-R., Hadjiakhoondi, A., Delazar, A., Ajani, Y., Tavakoli, S., & Yassa, N. (2015). Phytochemical and Antioxidant Investigation of the Aerial Parts of Dorema glabrum Fisch. & CA Mey. Iranian journal of pharmaceutical research: IJPR, 14(3), 925. https://doi.org/10.1007/s00044-014-1138-2
Dhamodiran, M., Chinnaperumal, K., Venkatesan, G., Alshiekheid, M. A., & Suseem, S. (2024). Isolation, structural elucidation of bioactive compounds and their wound-healing ability, antibacterial and in silico molecular docking applications. Environmental Research, 252, 119023. https://doi.org/10.1016/ j.envres.2024.119023
El Omari, N., Jaouadi, I., Lahyaoui, M., Benali, T., Taha, D., Bakrim, S., El Menyiy, N., El Kamari, F., Zengin, G., & Bangar, S. P. (2022). Natural Sources, Pharmacological Properties, and Health Benefits of Daucosterol: Versatility of Actions. Applied Sciences, 12(12), 5779. https://doi.org/10.3390/app12125779
Esmaeili, M. A., & Farimani, M. M. (2014). Inactivation of PI3K/Akt pathway and upregulation of PTEN gene are involved in daucosterol, isolated from Salvia sahendica, induced apoptosis in human breast adenocarcinoma cells. South African Journal of Botany, 93, 37-47. https://doi.org/10.1016/j.sajb.2014.03.010
Gao, C.-y., Lu, Y.-h., Tian, C.-r., Xu, J.-g., Guo, X.-p., Zhou, R., & Hao, G. (2011). Main nutrients, phenolics, antioxidant activity, DNA damage protective effect and microstructure of Sphallerocarpus gracilis root at different harvest time. Food chemistry, 127(2), 615-622. https://doi.org/10.1016/j.foodchem.2011.01.053
Gao, P., Huang, X., Liao, T., Li, G., Yu, X., You, Y., & Huang, Y. (2019). Daucosterol induces autophagic-dependent apoptosis in prostate cancer via JNK activation. Bioscience Trends, 13(2), 160-167. https://doi.org/10.5582/bst.2018.01293
Gökçimen, S. Ş., İpek, Y., Behçet, L., Demirtaş, İ., & Özen, T. (2024). Isolation, characterization and evaluation of oxypeucedanin and osthol from local endemic Prangos aricakensis Behçet and Yapar root as antioxidant, enzyme inhibitory, antibacterial and DNA protection: molecular docking and DFT approaches. Journal of Biomolecular Structure and Dynamics, 1-18. https://doi.org/10.1080/07391102.2024.2303387
Gu, Y., Yang, X., Shang, C., Thao, T. T. P., & Koyama, T. (2021a). Inhibition and interactions of alpha-amylase by daucosterol from the peel of Chinese water chestnut (Eleocharis dulcis). Food & Function, 12(18), 8411-8424. https://doi.org/10.1039/d1fo00887k
Gu, Y., Yang, X., Shang, C., Thao, T. T. P., & Koyama, T. (2021b). Inhibitory properties of saponin from Eleocharis dulcis peel against α-glucosidase. RSC advances, 11(25), 15400-15409. https://doi.org/10.1039/d1ra02198b
Jang, J., Kim, S.-M., Yee, S.-M., Kim, E.-M., Lee, E.-H., Choi, H.-R., Lee, Y.-S., Yang, W.-K., Kim, H.-Y., & Kim, K.-H. (2019). Daucosterol suppresses dextran sulfate sodium (DSS)-induced colitis in mice. International Immunopharmacology, 72, 124-130. https://doi.org/10.1016/j.intimp.2019.03.062
Lai, G. F., Wang, Y. F., Lu, C. H., Cao, J. X., Xu, Y. L., & Luo, S. D. (2003). Three novel triterpenoids from the aerial part of Helwingia chinensis. Helvetica Chimica Acta, 86(6), 2136-2141. https://doi.org/10.1002/hlca.200390170
Landgren, M., Oden, H., Kühn, I., Österlund, A., & Kahlmeter, G. (2005). Diversity among 2481 Escherichia coli from women with community-acquired lower urinary tract infections in 17 countries. Journal of antimicrobial Chemotherapy, 55(6), 928-937. https://doi.org/10.1093/jac/dki122
Lee, J.-H., Lee, J. Y., Park, J. H., Jung, H. S., Kim, J. S., Kang, S. S., Kim, Y. S., & Han, Y. (2007). Immunoregulatory activity by daucosterol, a β-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. Vaccine, 25(19), 3834-3840. https://doi.org/10.1016/ j.vaccine.2007.01.108
Li, T., Yin, X., Pan, W., Yang, J., & Liang, G. (2010). Chemical constituents of Humulus scandens. Zhong yao cai= Zhongyaocai= Journal of Chinese medicinal materials, 33, 55-57.
Marah, S., İpek, Y., Ozen, T., Demirtas, İ., & Behçet, L. (2025). Bioactivity-guided isolation of inositol as acetylcholinesterase inhibitory from endemic Campanula baskilensis Behcet: In vitro bioactivity, PCA analysis, and silico supporting studies. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, 28(3), 717-735. https://doi.org/10.18016/ksutarimdoga.vi.1632935
Mozaffarian, V. (1996). A dictionary of Iranian plant names. Tehran: Farhang Moaser, 396.
Nayel, N., Marah, S., Ozen, T., Yıldız, I., Erenler, R., & Behcet, L. (2024). Characterization and Comparative Investigation of In Vitro Bioactivities for Lactuca anatolica Root Aqueous Extract and Their Green-Chemical Synthesized Nanoparticles; Molecular Docking Studies. BioNanoScience, 14(3), 2854-2871. https://doi.org/10.1007/s12668-024-01353-9
Nguedia, M. Y., Tueche, A. B., Yaya, A. J. G., Yadji, V., Ndinteh, D. T., Njamen, D., & Zingue, S. (2020). Daucosterol from Crateva adansonii DC (Capparaceae) reduces 7, 12‐dimethylbenz (a) anthracene‐induced mammary tumors in Wistar rats. Environmental toxicology, 35(10), 1125-1136. https://doi.org/10.1002/tox.22948
Özek, G., Bedir, E., Tabanca, N., Ali, A., Khan, I. A., Duran, A., Başer, K. H., & Özek, T. (2018). Isolation of eudesmane type sesquiterpene ketone from Prangos heyniae H. Duman & MF Watson essential oil and mosquitocidal activity of the essential oils. Open Chemistry, 16(1), 453-467. https://doi.org/10.1515/chem-2018-0051
Peshin, T., & Kar, H. (2017). Isolation and Characterization of β-Sitosterol-3-O-β-D-glucoside from the Extract of the Flowers of Viola odorata. Br. J. Pharm. Res, 16(4), 1-8. https://doi.org/10.9734/bjpr/2017/33160
Pratt, R. (2008). Substrate specificity of bacterial DD-peptidases (penicillin-binding proteins). Cellular and Molecular Life Sciences, 65, 2138-2155. https://doi.org/10.1007/s00018-008-7591-7
Ramprasath, V. R., & Awad, A. B. (2015). Role of phytosterols in cancer prevention and treatment. Journal of AOAC International, 98(3), 735-738. https://doi.org/10.5740/jaoacint.sgeramprasath
Ruan, S., Tu, C.-H., & Bourne, C. R. (2024). Friend or Foe: Protein Inhibitors of DNA Gyrase. Biology, 13(2), 84. https://doi.org/10.3390/biology13020084
Schmidt, B., Ribnicky, D. M., Poulev, A., Logendra, S., Cefalu, W. T., & Raskin, I. (2008). A natural history of botanical therapeutics. Metabolism, 57, S3-S9. https://doi.org/10.1016/j.metabol.2008.03.001
Stefani, T., Garza-González, E., Rivas-Galindo, V. M., Rios, M. Y., Alvarez, L., & Camacho-Corona, M. d. R. (2019). Hechtia glomerata Zucc: Phytochemistry and activity of its extracts and major constituents against resistant bacteria. Molecules, 24(19), 3434. https://doi.org/10.3390/molecules24193434
Toner, E., Adalja, A., Gronvall, G. K., Cicero, A., & Inglesby, T. V. (2015). Antimicrobial resistance is a global health emergency. Health security, 13(3), 153-155. https://doi.org/10.1089/hs.2014.0088
Toubi, Y., Abrigach, F., Radi, S., Souna, F., Hakkou, A., Alsayari, A., Bin Muhsinah, A., & Mabkhot, Y. N. (2019). Synthesis, antimicrobial screening, homology modeling, and molecular docking studies of a new series of Schiff base derivatives as prospective fungal inhibitor candidates. Molecules, 24(18), 3250. https://doi.org/10.3390/ molecules24183250
Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455-461. https://doi.org/10.1002/jcc.21334
Vassallo, J., Besinis, A., Boden, R., & Handy, R. (2016). Evaluation of the minimum inhibition concentration (MIC) assay for environmental assessment of nanomaterials. https://doi.org/10.1016/j.toxlet.2016.06.1934
Wang, G.-Q., Gu, J.-F., Gao, Y.-C., & Dai, Y.-J. (2016). Daucosterol inhibits colon cancer growth by inducing apoptosis, inhibiting cell migration and invasion and targeting caspase signalling pathway. Bangladesh Journal of Pharmacology, 11(2), 395-401. https://doi.org/10.3329/bjp.v11i2.25754
Xu, C., Luo, Z., & Zhang, X. (2010). Progress in Computing Technology of Molecular Docking. 12th Annual Meeting of China Association for Science and Technology on Information and Communication Technology and Smart Grid,
Zhang, H., Song, Y., & Feng, C. (2020). Improvement of cerebral ischemia/reperfusion injury by daucosterol palmitate-induced neuronal apoptosis inhibition via PI3K/Akt/mTOR signaling pathway. Metabolic brain disease, 35, 1035-1044. https://doi.org/10.1007/s11011-020-00575-6
Zhao, C., She, T., Wang, L., Su, Y., Qu, L., Gao, Y., Xu, S., Cai, S., & Shou, C. (2015). Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner. Life sciences, 137, 37-43. https://doi.org/10.1016/j.lfs.2015.07.019

Details

Primary Language

Turkish

Subjects

Pharmaceutical Botany

Journal Section

Research Article

Authors

Serbay Şafak Gökçimen
0000-0002-3147-7042
Türkiye

Yaşar İpek
0000-0002-1041-267X
Türkiye

Tevfik Ozen ^*
0000-0003-0133-5630
Türkiye

İbrahim Demirtas
0000-0001-8946-647X
Türkiye

Lütfi Behçet
0000-0001-8334-7816
Türkiye

Early Pub Date

October 18, 2025

Publication Date

January 1, 2026

Submission Date

April 26, 2025

Acceptance Date

August 22, 2025

Published in Issue

Year 2026 Volume: 29 Number: 1

DOI

https://doi.org/10.18016/ksutarimdoga.vi.1683529

IZ

https://izlik.org/JA39ZH95XC

Cite

RIS / Bibtex

APA

Gökçimen, S. Ş., İpek, Y., Ozen, T., Demirtas, İ., & Behçet, L. (2026). Prangos aricakensis’ten izole edilen yeni olası antibakteriyel molekül, Daukosterol: Antibakteriyel aktivite ve DD-peptidaz ve giraz üzerinden moleküler yerleştirme yaklaşımları. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 29(1), 40-50. https://doi.org/10.18016/ksutarimdoga.vi.1683529