Türkiye'de yetişen bazı Tanacetum L. türleri üzerinde fitokimyasal araştırmalar ve biyoaktivite çalışmaları
Phytochemical and bioactivity studies on the some Tanacetum L. species growing in Turkey
Yazar: HÜSEYİN SERVİ
Danışman: PROF. DR. ZEHRA NÜKET ÖCAL SUNGUROĞLU ; PROF. DR. NEZHUN GÖREN
Yıldız Teknik Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı / Organik Kimya Bilim Dalı
Derece: Doktora, 2016
Konu: Kimya = Chemistry
Dizin: Antioksidanlar = Antioxidants ; Biyolojik aktivite = Biological activity

Özet:
Bitkiler yetiştikleri doğal ortamlardan Prof.Dr. Nezhun Gören ve arkadaşları tarafından farklı yıllarda toplanmıştır. Tanacetum balsamita L. ssp. balsamitoides (Schultz Bip.) Grierson (ISTE 79241a) bitkisi Van, Güzeldere, Çuh Gediği'nden 2000 yılında, Tanacetum mucroniferum Hub.-Mor.& Grierson (ISTE 85425) bitkisi Erzincan, Sakaltutan yöresinden 2008 yılında toplanmıştır. Bitkiler laboratuarda uygun koşullarda kurutulmuş, sırasıyla hekzan, etil asetat ve metanol ekstreleri elde edilmiştir. 
Bu çalışmada, bitkilerin etil asetat ve metanol ekstreleri üzerine karşılaştırmalı olarak fitokimyasal araştırmalar yapılmıştır. Etil asetat ve metanol ekstrelerinden kolon kromatografisi, MPLC, HPTLC ve Preparatif İnce Tabaka kromatografisi gibi kromatografik yöntemler kullanılarak sekonder metabolitler izole edilmiş ve saflaştırılmıştır. Sekonder metabolitlerin stereokimyasal yapıları UV, IR, NMR (1H-NMR,13C-NMR, APT, COSY, HMBC, HSQC, NOESY), MS (EI, CI, HR) ve bazı kimyasal reaksiyonlarla belirlenmiştir. İzolasyon çalışmalarında dördü yeni olmak üzere toplam kırk üç madde elde edilmiş ve yapıları aydınlatılmıştır. Tanacetum balsamita L. ssp. balsamitoides bitkisinin etil asetat ekstresinden 1α-Acetoxy-11β(H),13-dihydrodouglanin, Taurin, β-Sitosterol, Santonin, Chrysanthemolide, Pallensis, 1-Acetylerivanin, 1,10-Epoxyspiciformin, 8α-Hydroxysantamarin, Tamirin, 1α-Acetoxy-3-epi-erivanin, Artemin, Artesin, Germacranolide with an 1,5-ether linkage, 1α-Hydroxy-deacetylirinol-4α,5β-epoxide, 1α,8α-Dihydroxy-10-epi-arbusculin A, Tavulin, 5-Hydroxy-3′,4′,6,7-tetramethoxyflavone, Cirsilineol, 5,3′-Dihydroxy-6,7,4′,5′-tetramethoxyflavone, Umbelliferone maddeleri izole edilmiştir. 1α-Acetoxy-3-epi-erivanin maddesi doğal bir kaynaktan ilk defa tarafımızdan izole edilmiştir. Tanacetum balsamita L. ssp. balsamitoides bitkisinin MeOH ekstresinden Chrysanthemolide, Pallensis, 1,10-Epoxyspiciformin, Taurin, 1-Acetylerivanin, Tavulin, Tanachin, Deacetyl-β-cyclopyrethrosin, Cirsimaritin, 5,7,3′-Trihydroxy-6,4′,5′-trimethoxyflavone, Isofraxidin, 7-Methoxycoumarin ve Scopoletin maddeleri izole edilmiştir. Tanacetum mucroniferum bitkisinin etil asetat ekstresinden Arsanin, 9α-Acetoxyartecanin, Mucronolide, Ajanolide A Epoxide, α-Amyrin, Salvigenin, 5-Hydroxy-3′,4′,6,7-tetramethoxyflavone, Cirsilineol, Scoparone, Cirsimaritin, Jaceosidin, 5,3′,4′-Trihydroxy-3,6,7,5′-tetramethoxyflavone maddeleri izole edilmiştir. Mucronolide ve Ajanolide A epoxide maddeleri doğal bir kaynaktan ilk defa tarafımızdan izole edilmiştir. Tanacetum mucroniferum bitkisinin MeOH ekstresinden 1α,3β,10α-Trihydroxy-7α,11αH-germacra-4-en-12-6α-olide, Ajanolide A epoxide, Mucronolide, Scopoletin, Umbelliferone, Scoparone, 5-Hydroxy-3′,4′,6,7-tetramethoxyflavone maddeleri izole edilmiştir. 1α,3β,10α-Trihydroxy-7α,11αH-germacra-4-en-12-6α-olide maddesi doğal bir kaynaktan ilk defa tarafımızdan izole edilmiştir.
Tanacetum mucroniferum bitkisinin toprak üstü kısımlarından elde edilen ve GC/MS ile bileşimi belirlenen uçucu yağın asetilkolinesteraz inhibisyonu, antioksidan ve sitotoksik aktiviteleri araştırılmıştır. Bitkinin uçucu yağı yüksek oranda asetilkolinesteraz inhibisyonu göstermiştir. Uçucu yağ çok düşük oranda PRAP (Phosphomolybdenum Reducing Antioxidant Power) antioksidan aktivite göstermiş ve hücre hatlarına karşı herhangi bir sitotoksik aktivite göstermemiştir.

Abstract:
The plants were collected from their natural habitats in different years by Prof.Dr.Nezhun Gören and her colleagues. Tanacetum balsamita L. ssp. balsamitoides (Schultz Bip.) Grierson was collected from Güzeldere-Çuh breach (Van) in 2000, Tanacetum mucroniferum Hub.-Mor.& Grierson was collected from Sakaltutan region (Erzincan) in 2008. The plants were dried at appropriate conditions in the laboratory. The dried plants were extracted with hexan, ethylacetate and methanol respectively. 
Comparative phytochemical investigation was carried out on the ethylacetate and methanol extracts of the plants. The secondary metabolites were isolated and purified by means of chromatographic methods such as column chromatography (CC), Medium Pressure Liquid Chromatography (MPLC), High Pressure Thin Layer Chromatography (HPTLC), preparative thin layer chromatography (TLC). Stereochemical structure of secondary metabolites were identified by means of spectral methods such as UV, IR, NMR (1H-NMR,13C- NMR, APT, COSY, HMBC, HSQC, NOESY), MS (EI, CI, HR) and some chemical reactions were carried out. Totally forty three compounds were isolated four of them being new. Their structures were determined by spectral methods. 1α-Acetoxy-11β(H),13-dihydrodouglanin, Taurin, β-Sitosterol, Santonin, Chrysanthemolide, Pallensis, 1-Acetylerivanin, 1,10-Epoxyspiciformin, 8α-Hydroxysantamarin, Tamirin, 1α-Acetoxy-3-epi-erivanin, Artemin, Artesin, Germacranolide with an 1,5-ether linkage, 1α-Hydroxy-deacetylirinol-4α,5β-epoxide, 1α,8α-Dihydroxy-10-epi-arbusculin A, Tavulin, 5-Hydroxy-3′,4′,6,7-tetramethoxyflavone, Circilineol, 5,3′-Dihydroxy-6,7,4′,5′-tetramethoxyflavone and Umbelliferone were isolated from the ethylacetate extract of Tanacetum balsamita L. ssp. balsamitoides. 1α-Acetoxy-3-epi-erivanin was isolated from a natural source for the first time by us. Chrysanthemolide, Pallensis, 1,10-Epoxyspiciformin, Taurin, 1-Acetylerivanin, Tavulin, Tanachin, Deacetyl-β-cyclopyrethrosin, Cirsimaritin, 5,7,3′-Trihydroxy-6,4′,5′-trimethoxyflavone, Isofraxidin, 7-Methoxycoumarin and Scopoletin were isolated from the methanol extract of Tanacetum balsamita L. ssp. balsamitoides. Arsanin, 9α-Acetoxyartecanin, Mucronolide, Ajanolide A epoxide, α-Amyrin, Salvigenin, 5-Hydroxy-3′,4′,6,7-tetramethoxyflavone, Cirsilineol, Scoparone, Cirsimaritin, Jaceosidin, 5,3′,4′-Trihydroxy-3,6,7,5′-tetramethoxyflavone were isolated from the ethylacetate extract of Tanacetum mucroniferum. Mucronolide and  Ajanolide A epoxide were isolated from a natural source for the first time by us. 1α,3β,10α-Trihydroxy-7α,11αH-germacra-4-en-12-6α-olide, Ajanolide A epoxide, Mucronolide, Scopoletin, Umbelliferone, Scoparone, 5-Hydroxy-3′,4′,6,7-tetramethoxyflavone were isolated from the methanol extract of Tanacetum mucroniferum.1α,3β,10α-Trihydroxy-7α,11αH-germacra-4-en-12-6α-olide was isolated from a natural source for the first time by us.
Composition of the essential oils obtained from flowers of Tanacetum mucroniferum was determined by GC/MS. The essential oil was investigated for their acetylcholinesterase inhibition, PRAP antioxidant and cytotoxic activities. The essential oil of Tanacetum mucroniferum showed high acetylcholinesterase inhibition. The essential oil showed very low PRAP (Phosphomolybdenum Reducing Antioxidant Power) acitivity and didn't show considerable cytotoxic activity against cell lines.