Cytotoxic Activities of Isolated Compounds from Prangos uechtritzii Boiss & Hausskn

Year 2024, Issue: Special Issue / International Multidisciplinary Symposium on Drug Research and Development, DRD-2023, 27 - 33, 01.07.2024

Gökay Albayrak Fadime Aydın Köse Şüra Baykan

https://doi.org/10.52794/hujpharm.1372020

Abstract

Prangos uechtritzii Boiss&Hausskn is an endemic plant of Türkiye, and the
plant roots are rich in coumarins. This study aims to evaluate the cytotoxic activities
of the 16 natural compounds along with the n-hexane (PH), chloroform
(PC), and methanol (PM) extracts of P. uechtritzii. For this purpose, fourteen
coumarin derivatives; umbelliferone(1), 6-formylumbelliferone(2), suberosin(3),
7-demethylsuberosin(4), (+)-ulopterol(5), tamarin(6), psoralen(7), imperatorin(
8), (+)-oxypeucedanin(9), (+)-oxypeucedanin hydrate(10), (+)-oxypeucedanin
methanolate(11), (+)-marmesin(12), (-)-prantschimgin(13), and (-)-adicardin(
14); two polyacetylenes (-)-panaxynol(15), (+)-falcarindiol(16) and three
extracts (PH, PC, and PM) were tested for their cytotoxicity against two healthy
(HK-2, NIH/3T3), and four cancer (MCF-7, A-549, SH-SY5Y, PC-3) cells by
WST-1 method. Doxorubicin was used as a positive control. PH and PC showed
cytotoxic effects on all the cell lines with IC50 values of 8.16-91.56 μg/mL.
PH displayed a selective effect on SH-SY5Y cells [Selectivity Index (SI)= 2.5]
compared to NIH/3T3. PC exhibited cytotoxic effects on PC-3 cells (SI=2) compared
to both NIH/3T3, and HK-2. PM didn’t display cytotoxicity at 100 μg/mL.
(-)-Panaxynol, (+)-falcarindiol, 6-formylumbelliferone, 7-demethylsuberosin,
and suberosin exhibited effects with IC50 values of 8.65-87.91 μM, while others
didn’t work at 100 μM. So, P. uechtritzii could be a promising natural source in
the development of new drugs for cancer treatment.

Keywords

Prangos uechtritzii, coumarin, cytotoxicity

Ethical Statement

The authors declare that there are no conflicts of interest.

Supporting Institution

TÜBİTAK

Project Number

219S127

Thanks

This study was supported by TUBITAK (The Scientific and Technological Research Council of Türkiye) under Grant number: 219S127.

Prangos uechtritzii Boiss & Hausskn'dan İzole Edilmiş Bileşiklerin Sitotoksik Aktiviteleri

Abstract

Prangos uechtritzii Boiss&Hausskn Türkiye'nin endemik bir bitkisidir ve bitki kökleri kumarinler açısından zengindir. Bu çalışma, P. uechtritzii'nin n-hekzan (PH), kloroform (PC) ve metanol (PM) ekstreleri ile birlikte 16 doğal bileşiğin sitotoksik aktivitelerini değerlendirmeyi amaçlamaktadır. Bu amaçla on dört kumarin türevi; umbelliferon(1), 6-formilumbelliferon(2), suberosin(3), 7-demetilsuberosin(4), (+)-ulopterol(5), tamarin(6), psoralen(7), imperatorin(8), (+ )-oksipösedanin(9), (+)-oksipösedanin hidrat(10), (+)-oksipösedanin metanolat(11), (+)-marmesin(12), (-)-prantşimgin(13) ve (-)- adikardin(14); iki poliasetilen (-)-panaksinol(15), (+)-falkarindiol(16) ve üç ekstre (PH, PC ve PM), iki sağlıklı (HK-2, NIH/3T3) ve dört kanserli (MCF-7, A-549, SH-SY5Y, PC-3) hücre hattına karşı WST-1 yöntemi kullanılarak sitotoksisite açısından test edilmiştir. Pozitif kontrol olarak doksorubisin kullanılmıştır. PH ve PC, 8.16-91.56 µg/mL IC50 değerleriyle tüm hücre hatlarında sitotoksik etki göstermiştir. PH, NIH/3T3'e kıyasla SH-SY5Y hücreleri üzerinde seçici bir etki göstermiştir [Seçicilik İndeksi (SI)= 2.5]. PC, hem NIH/3T3 hem de HK-2 ile karşılaştırıldığında PC-3 hücreleri (SI=2) üzerinde sitotoksik etkiler sergilemiştir. PM 100 µg/mL'de sitotoksisite göstermemiştir. (-)-Panaksinol, (+)-falkarindiol, 6-formilumbelliferon, 7-demetilsuberosin ve suberosin, IC50= 8.65-87.91 µM değerlerinde etkiler sergilerken diğerleri 100 µM'de etki göstermemiştir. Sonuçlara göre P. uechtritzii, kanser tedavisine yönelik yeni ilaçların geliştirilmesinde umut verici bir doğal kaynak olabilir.

Keywords

Prangos uechtritzii, kumarin, sitotoksisite

Project Number

219S127

References

• 1. Albayrak G, Demir S, Kose FA, Baykan S. New coumarin glycosides from endemic Prangos heyniae H. Duman & M.F. Watson. Nat Prod Res. 2023;37(2):227–39.
• 2. Bulut G, Tuzlacı E, Doğan A, Şenkardes I. An ethnopharmacological review on the Turkish Apiaceae species. J Fac Pharm Istanbul Univ. 2014;44(2):163–79.
• 3. Menemen Y. Türkiye bitkileri listesi:(damarlı bitkiler). 1st ed. Guner A, editor. İstanbul: Nezahat Gökyiğit Botanik Bahçesi Yayınları; 2012. 75–76 p.
• 4. Mottaghipisheh J, Kiss T, Tóth B, Csupor D. The Prangos genus: A comprehensive review on traditional use, phytochemistry, and pharmacological activities. Phytochem Rev. 2020;19:1449–70.
• 5. Zengin G, Mahomoodally MF, Yıldıztugay E, Jugreet S, Khan SU, Dall’Acqua S, et al. Chemical composition, biological activities and in silico analysis of essential oils of three endemic Prangos species from Turkey. Molecules. 2022;27(5):1676.
• 6. Dall’Acqua S, Sut S, Zengin G, Peron G, Elbasan F, Yildiztugay E, et al. Phytochemical screening, antioxidant, and enzyme inhibitory properties of three Prangos species (P. heyniae, P. meliocarpoides var. meliocarpoides, and P. uechtritzii) depicted by comprehensive LC-MS and multivariate data analysis. Antioxidants. 2022;11(9):1712.
• 7. Uzel A, Dirmenci T, Çelik A, Arabacı T. Composition and antimicrobial activity of Prangos platychlaena and P. uechtritzii. Chem Nat Compd. 2006;42(2):169–71.
• 8. Başer KHC, Demirci B, Demirci F, Bedir E, Weyerstahl P, Marschall H, et al. A new bisabolene derivative from the essential oil of Prangos uechtritzii fruits. Planta Med. 2000;66(7):674–7.
• 9. Zidorn C, Jöhrer K, Ganzera M, Schubert B, Sigmund EM, Mader J, et al. Polyacetylenes from the Apiaceae vegetables carrot, celery, fennel, parsley, and parsnip and their cytotoxic activities. J Agric Food Chem. 2005 Apr 6;53(7):2518–23.
• 10. Albayrak G, Demir S, Koyu H, Baykan S. Anticholinesterase compounds from endemic Prangos uechtritzii. Chem Biodivers. 2022;19:e202200557.
• 11. Alan E, Albayrak G, Sevin G, Yetik-Anacak G, Baykan S. Relaxation mechanisms of chloroform root extracts of Prangos heyniae and Prangos uechtritzii on mouse corpus cavernosum. Andrologia. 2022;54(11):e14604.
• 12. Nematollahi-Mahani SN, Rezazadeh-Kermani M, Mehrabani M, Nakhaee N. Cytotoxic effects of Teucrium polium. on some established cell lines. Pharm Biol. 2007;45(4):295–8.
• 13. Lopachin RM, Gavin T. Molecular mechanisms of aldehyde toxicity: A chemical perspective. Chem Res Toxicol. 2014;27(7):1081–91.
• 14. Gacche RN, Jadhav SG. Antioxidant activities and cytotoxicity of selected coumarin derivatives: Preliminary results of a structure-activity relationship study using computational tools. J Exp Clin Med. 2012;4(3):165–9.
• 15. Cheung SSC, Hasman D, Khelifi D, Tai J, Smith RW, Warnock GL. Devil’s club falcarinol-type polyacetylenes inhibit pancreatic cancer cell proliferation. Nutr Cancer. 2019;71(2):301– 11.
• 16. Meot-Duros L, Cérantola S, Talarmin H, Le Meur C, Le Floch G, Magné C. New antibacterial and cytotoxic activities of falcarindiol isolated in Crithmum maritimum L. leaf extract. Food Chem Toxicol. 2010 Feb 1;48(2):553–7.
• 17. Young JF, Duthie SJ, Milne L, Christensen LP, Duthie GG, Bestwick CS. Biphasic effect of falcarinol on CaCo-2 cell proliferation, DNA damage, and apoptosis. J Agric Food Chem. 2007 Feb 7;55(3):618–23.
• 18. G. Zaini R, Brandt K, R. Clench M, L. Le Maitre C. Effects of bioactive compounds from carrots (Daucus carota L.), polyacetylenes, beta-carotene and lutein on human lymphoid leukaemia Cells. Anticancer Agents Med Chem. 2012 Jun 5;12(6):640–52.
• 19. Stig P, Eric L, Christensen LP. Differential effects of falcarinol and related aliphatic C-17-polyacetylenes on intestinal cell proliferation. J Agric Food Chem. 2009 Sep 23;57(18):8290– 6.
• 20. Jin HR, Zhao J, Zhang Z, Liao Y, Wang CZ, Huang WH, et al. The antitumor natural compound falcarindiol promotes cancer cell death by inducing endoplasmic reticulum stress. Cell Death Dis. 2012 Aug 23;3(8):e376–e376.
• 21. Quan CC, Lee JP, Jin WY, Youn UJ, Kim HJ, Ik SL, et al. Cytotoxic constituents from Angelicae sinensis radix. Arch Pharm Res. 2007 May 31;30(5):565–9.