Telah dilakukan kuantifikasi kandungan fenolat total, flavonoid total, uji aktivitas antioksidan (DPPH), serta identifikasi secara kromatografi senyawa fenolat dari golongan kumarin dalam fraksi ...n-heksana Pimpinella alpina Molk. Hasil penelitian menunjukkan bahwa kandungan senyawa fenolat total fraksi n-heksana , yaitu 45,04 mg ekuivalen asam galat/gram fraksi kering. Sedangkan kandungan flavonoid total fraksi n-heksana yaitu 5,58 mg ekuivalen kuersetin/gram fraksi kering. Aktivitas antioksidan dengan metode DPPH diperoleh IC50 yaitu 13485 ppm. Identifikasi dari golongan kumarin dari kromatografi kolom dihasilkan 11 fraksi, berdasarkan hasil profil KLT setelah disemprot dengan pereaksi warna NH3 dan dilihat di bawah lampu UV 365 nm, ditunjukkan bahwa fraksi F1 positif mengandung golongan senyawa kumarin yang ditunjukkan oleh noda berwarna hijau kuning. Bagaimanapun struktur kimia dari senyawa tersebut hingga saat ini belum dapat diusulkan.
The series of seventeen 4-hydroxycoumarin derivatives, substituted at C-3 position with high polar scaffolds, were evaluated as antimicrobial, antioxidant and anticoagulant agents. The in vitro ...antimicrobial activity of compounds 1-10s was determined using the dilution method. During the evaluation of antimicrobial activity, coumarin derivatives showed moderate potential. The compounds 1-10s antioxidant activity in vitro was determined using Total antioxidant capacity assay, DPPH radical scavenging assay, Lipid peroxidation in linoleic acid emulsion inhibition assay, Hydroxyl radical scavenging activity assay and Ferrous ion chelating ability assay. During the evaluation of antioxidant activity, coumarin derivatives presented excellent activity. The anticoagulant activity in vivo was evaluated after the continuous intraperitoneal administration of compounds 1-10s to adult Albino Wistar rats and by measuring the prothrombin time. Administrated compounds presented excellent anticoagulant activity and induced no inflammation or change to the animal liver. Biological results were correlated with various molecular descriptors, obtained after molecular-mechanic and quantum-mechanic optimization of coumarin compounds, which led to eight statistically significant 1D-QSAR equations, describing the antimicrobial (by three equations) and antioxidant activity (by five equations), and two statistically significant 3DQSAR models describing the anticoagulant activity. Obtained QSAR model were used for design of fourthly six new derivatives with improved activity. The antimicrobial activity was predicted for ten new compounds, the antioxidant ability for twenty more, while the anticoagulant activity was proposed for sixteen new derivatives. QSAR studies were accompanied with homology modeling and molecular docking studies, as well with the DFT mechanistic studies which were all used for describing the high biological activity of tested compounds.
Serija od sedamnaest derivata 4-hidroksikumarina, supstituisanih u položaju 3 polarnim funkcionalnim grupama, testirani su kao antimikrobni, antioksidativni i antikoagulativni agensi. Antimikrobna aktivnost testiranih derivata 1-10s određena je dilucionom metodom u in vitro uslovima pri čemu su derivati pokazali umerenu aktivnost. Antioksidativna aktivnost in vitro derivata 1-10s određena je konstatovanjem totalnog antioksidativnog kapaciteta, sposobnosti neutralizacije DPPH, peroksidnog i hidroksi radikala i helatizacionog kapaciteta testiranih agenasa, pri čemu su svi derivati pokazali izrazitu antioksidativnu aktivnost. Antikoagulativna aktivnost in vivo derivata 1-10s ispitivana je nakon intraperitonealne aplikacije derivata na laboratorijskim pacovima Wistar soja i merenjem protrombinskog vremena. Derivati 1-10s pokazali su odličnu antikoagulativnu aktivnost nakon višednevne aplikacije, nisu izazvali inflamaciju niti promene na jetri životinja. Biološki rezultati su, nakon optimizacije jedinjenja molekulsko-mehaničkim i kvantno-mehaničkim metodama, poređeni sa njihovim fizičko-hemijskim parametrima, odnosno molekulskim deskriptorima, što je rezultovalo formiranjem osam statistički značajnih 1D-QSAR jednačina koje su obuhvatile studije antimikrobne (tri jednačine) i antioksidativne aktivnosti (pet jednačina), odnosno dva statistički značajna 3D-QSAR modela koji su obuhvatili studije antikoagulativne aktivnosti. QSAR studije iskorišćene su pri dizajnu četrdeset šest novih aktivnijih derivata. Antimikrobna aktivnost predviđena je za deset novih derivata, antioksidativna za dvadeset, dok je za šesnaest novih derivata predviđen nivo antikoagulativne aktivnosti. QSAR studije upotpunjenje su i studijama homologog modelovanja, molekulskog dokovanja i DFT mehanističkim studijama u cilju dodatnog objašnjenja visoke aktivnosti testiranih derivata.
Kumarin i njegovi derivati su široko rasprostranjeni u prirodi i nalazimo ih u mnoštvu različitih biljaka, voća i povrća. Kumarin i njegovi derivati pokazuju niz bioloških aktivnosti, međutim njegova ...upotreba je ograničena, a dopuštena koncentracija u namirnicama određena zakonom. Vrlo su se često kao model za proučavanje toksičnosti kumarina koristili štakori, ali novija istraživanja pokazuju da je metabolizam, a samim time i štetnost kumarina, kod ljudi i štakora, različita. Ovaj rad daje pregled osnovnih bioloških svojstava kumarina i njegovih derivata, kao i opis i specifičnosti metabolizma kumarina kod ljudi u odnosu na štakore.
Euphorbia heteradena Jaub. & Spach (Euphorbiaceae), a plant endemic to Turkey, has not been investigated previously. The $CH_2Cl_2$ extract of the aerial parts of Euphorbia heteradena yielded ...24-methylenecycloartanol, cycloart-25-en-3$\beta$ ,24-diol, cycloart-22-en-$3\beta$ ,25-diol, vomifoliol, vomifoliol 9-O-$\beta$ -D-glucopyranoside, 3,4,3'-tri-O-methoxy ellagic acid, syringic acid and scopoletin. The structures of the isolates were identified by high field spectroscopic methods including 1D and 2D NMR techniques.
Benzopiran kumarinleri doğal bitkilerden sentezlenen ve pek çok özellik gösteren önemli bileşiklerdir.
Bu moleküller, kromofor özelliklerinden dolayı en çok boya kimyasında kullanılmaktadırlar.
...Kuvvetli oksijen köprüleri içeren bu makro halkalı bileşikler, alkali ve toprak alkali metaller ile (+)
yüklü kompleksler oluşturmaktadırlar. Pedersen, yüksek seçiciliği olan taç eter moleküllerin keşfi
ve kullanımı ile ilgili olarak yaptığı çalışmalardan ötürü 1987 Nobel Kimya ödülünü almıştır.
Kumarin türevlerinin optik özellikleri ile makro halkalı taç eterlerin katyon bağlama özelliklerini
bir araya getirerek uygulama alanlarını genişletmek üzere Tiftikçi ve Erk tarafından bir seri molekül
sentezlenmiştir (Tiftikçi ve Erk,2004). Literatüre son yıllarda kazandırılan bu moleküllerin
elektronik ve optik özelliklerinin bilinmesi daha sonra yapılacak olan sentezlere de ışık tutacaktır.
Bu özelliklerin teorik yöntemlerle anlaşılmasına yönelik yapılan bu çalışmada ayrıca kumarin halkasının
makro halkaya bağlanma pozisyonuna, kumarin halkası üzerindeki sübstitüsyona, makro
halka büyüklüğüne ve katyonun büyüklüğüne bağlı olarak moleküllerin UV soğurma spektrumlarındaki
ve katyon bağlama enerjilerindeki değişiklikler de incelenmiştir. Bağlanma enerjileri ya da
moleküllerin iyon seçiciliği $Li^+, Na^+, ve K^+$ iyonları için Yoğunluk Fonksiyoneli Teorisi (YFT) yöntemiyle
B3LYP/6-31g(d) seviyesinde gaz fazında, su ve asetonitril için ortamın dielektrik sabiti değiştirilerek
çözücü ortamında hesaplanmıştır. Elde edilen sonuçlar mevcut olan deneysel sonuçlarla
karşılaştırılmıştır. Katyonlu ve katyonsuz moleküllerin 0 Kelvin'deki gaz fazı ve çözücüye göre düzeltilmiş
elektronik enerjileri, sıfır enerjisi göz önüne alınarak hesaplanmıştır. Katyon bağlama reaksiyonunun
entalpisi ve serbest enerjisi ise baz fonksiyonundan gelen hatalara göre düzeltilerek
rapor edilmiştir. Bağlanma enerjilerinin daha yüksek bazda tekrarlanan hesaplarla baz fonksiyonuna
bağlı olarak nasıl değiştiği incelenmiştir.
The coumarins of benzopyran are important compounds
which are synthesized from natural plants
and have a good number of features. These molecules
are mostly used at dye chemistry because of
their chromophoric features. Macrocyclic ether
molecules which are known as good cation binding
compounds, are first discovered in 1967 by Charles
J. Pedersen who won 1/3 of the Chemistry Nobel
Prize for the development and use of molecules with
structure-specific interactions of high selectivity
These molecules contain strong oxygen bridges and
have a tendency to form positively charged complexes
with alkaline and soil alkaline metals in solution.
Being aware of the electronic and optical features
of these molecules, which have been shown
recent literatures, will illuminate the forthcoming
syntheses. To bring optical features of the coumarin
derivatives and the cation binding features of macrocyclic
crown ethers together, a series of new
molecules are synthesized by Tiftikçi and Erk to expand
the application areas of both type of molecules
(Tiftikçi; Erk, 2004). In this study which is done to
understand these features with theoretical methods,
the binding position of the coumarin to the macrocyclic,
the substitution on the coumarin, the magnitude
of macrocyclic and according to the magnitude
of the cation, the changes on the UV absorption
spectrums of molecules and the cation binding energy
are also analyzed. The energy of binding or the
ion selectivity of the molecules are calculated with
the following methods; for $Li^+, Na^+, ve K^+$ ions with
the method of DFT (Density Functional Theory) at
the B3LYP/6-31g(d) level at gas phase, for water
and asetonitril, by changing the constant dielectric
at the solvent medium. The outcomes which are yield
are compared with the existing experimental outcomes.
The gas phase at the 0 Kelvin of the molecules
with and without cations and their corrected
electronic energy according to the solvent are calculated
by regarding the zero energy. Also, the enthalpies
and free energy of the cation binding reaction
are reported by correcting according to the errors
coming from the base function (BSSE). Depending
on the base function, how the binding energies
change with repeated calculations at a higher base
is examined.
In this study cationic recognition of the computerized
form of crown ethers, which were synthesized
before, has been investigated. For that reason optimization
of the molecules has been carried out. Geometries
of the studied molecules optimized using
Density Functional Theory method (Devlin vd,
1994,1996) B3LYP (Becke 3 Parameter Lee-Yang-
Parr) functional (Lee vd, 1998), and 6-31g(d) bases
functional. Using optimized molecules with Time
Dependent Density Functional Theory methods Exited
states were optimized. Using exited states values
which were computed by TDDFT method, UV
graphics drawn with a computer software written in
Fortran. The attained values are normalized to 1
and graphs are plotted according to wave lengths.
UV spectra peaks are analyzed to find source and
reasons of the peak it could happen is investigated
(Erk vd., 1998). To investigate interactions with Na+
cation, BSSE correlation energy method used for
calculation of reaction energies. To investigate effect
of solvent water and asetonitril used as solvent.
Reaction energies of water and asetonitril were also
calculated. Attained results are compared with the
experimental results. To confirm optimized geometries,
experimental X-ray results of 18crown6 Na+
molecules compared with results of the study.
There is a concordant between experimental X-Ray
data and theoretical optimized geometry. So the
method applied in this study has been chosen correctly
for those molecules'. For studies carried out
in asetonitril, when UV peaks are compared with
experimental data, it has been understood that there
is accommodation between them. With comparing
experimental and theoretical data It has been tried
to proof the correctness of the applied methods.
These evidences could be used in further studies as
basis. The UV absorption is shifted to visible region
when coumarin ring is added to alone crown ethers.
For that reason the optical properties of crown
ethers can be investigated. Moreover if coumarin
rings are added to aromatic groups like phenyl, the
maximum UV peaks are shifted to red region. If
more functional groups are added to the crown ether
ring, the cation binding energy of the crown ether
will decrease. For that reason cation binding also
decreases.
U ovom radu je izvršena sinteza derivata kumarina s potencijalnom antifungalnom i antioksidacijskom aktivnošću. Naime, prema dosadašnjim istraživanjima, pretpostavlja se da se sintetskom ...modifikacijom polaznog spoja 7-hidroksi-4-metilkumarina mogu poboljšati njegova antifungalna i antioksidacijska svojstva. Sintetskim putem dobivena je serija Schiffovih baza s različitim supstituentima, kao i tiosemikarbazida i tiazolidinona. Antioksidacijska aktivnost je ispitana DPPH metodom spektrofotometrijski, EPR-om (DPPH i galvinoksil radikal) i fosfomolibden metodom. Rezultati su pokazali da se supstitucijom hidroksilne skupine 7-hidroksi-4-metilkumarina može značajno povećati antioksidacijska aktivnost polaznog kumarina, osobito prisutnošću supstituenata koji sadrže dihidroksifenilnu skupinu i tiosemikarbazidnu skupinu. Derivati kumarina su ispitani i na antifungalno djelovanje prema najčešćim plijesnima namirnica, Aspergillus flavus, A. ochraceus, Fusarium graminearum i F. verticillioides. Novosintetizirani derivati kumarina su se pokazali i kao izvrsna antifungalna sredstva, osobito Schiffove baze s hidroksilnim skupinama, te su, ovisno o primijenjenoj plijesni, pokazali i 100% inhibiciju rasta pojedine plijesni. Supstitucijom 7-hidroksi-4-metilkumarina u položaju 7 antifungalna aktivnost prema ispitanim plijesnima, osobito prema F. verticillioides, se povećala u odnosu na polazni kumarin. Spojevi koji u isto vrijeme posjeduju izvrsnu antioksidacijsku i antifungalnu aktivnost su Schiffove baze s dihidroksifenilnom skupinom i tiosemikarbazidi s fenilnom skupinom (supstituiranom ili ne).
In this work synthesis of coumarin derivatives with potential antifungal and antioxidant activity was performed. According to recent research work, synthethic modification of 7-hydroxy-4-methylcoumarin can improve its antifungal and antioxidant activity. A series of new coumarin derivatives, Schiff bases, thiosemicarbazides and thaizolidinones was prepared by conventional synthetic routes. Antioxidant activity of the compounds was evaluated using DPPH radical scavenging method, which was performed spectrophotometrically, by EPR spectroscopy (DPPH radical and galvinoxyl radical) and phosphomolybdenum method. The results indicated that the substitution of hydroxyl group of 7-hydroxy-4-methylcoumarin with dihidroxyphenyl or thiosemicarbazide group can increase an antioxidant activity of the starting compound. Antifungal investigation of coumarin derivatives against most relevant mycotoxigenic food molds, Aspergillus flavus, A. ochraceus, Fusarium graminearum and F. verticillioides, was also performed. The results revealed strong antifungal properties of the derivatives, Schiff bases especially. Several compounds effected a 100% inhibition against selected fungi, especially Schiff bases containing hydroxyl groups. Substitution of 7-hydroxy-4-methylcoumarin in position 7 can increase antifungal activity of the starting compound, especially against F. verticillioides. Compounds showing potent antioxidant and antifungal activity were Schiff bases with dihydroxyphenyl substituents and thiosemicarbazides with unsubstituted or substituted phenyl groups.
U radu je opisana sinteza estera aminokiselina s kumarinskim ostatkom 3-15. Ispitano je antivirusno djelovanje sintetiziranih spojeva na HIV-1 i goveđi virus diareje (BVDV) te in vitro citotoksičnost ...spojeva 3-10 i 12 na tumorskim linijama CD4 humanih T-stanica. Spoj 14 pokazao je inhibiciju HIV-1 s EC50 > 1.6 microg mL-1, dok je spoj 9 djelotvoran na leukemiju (MT4) s CC50 = 24 micromol L-1.
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