Synthesis and Evaluation of In Vitro Cytotoxic Activities of 3-Arylcoumarins Dertivatives in Cancer Cell Lines
Başlık:
Synthesis and Evaluation of In Vitro Cytotoxic Activities of 3-Arylcoumarins Dertivatives in Cancer Cell Lines
Yazar:
Gbadebo, Akintunde J., author.
ISBN:
9780438009998
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (98 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Musiliyu Musa; Lekan Latinwo Committee members: James Adams; LeeShawn Thomas.
Özet:
Coumarin and derivatives are vastly distributed in nature, exhibiting wide varieties of pharmacological activities. As a member of benzopyrone family of compounds, coumarins have attracted much interest in their synthesis and applications in treatment of various diseases. Numerous studies have shown that the biological, pharmacological and therapeutic properties of coumarins depending on the nature of group present and their pattern of substitutions of group(s) present on the core coumarin ring.
In this present investigation, a series of 7,8-diacetylated, 7,8-hydroxylated and un-substituted 3-arylcoumarin derivatives (47-53 and 55-68) were synthesized as potential anticancer agents using a modified Perkins and hydrolysis reaction method. All synthesized compounds were evaluated for their in-vitro cytotoxic effect on human liver (HepG2) and lung (A549) cancer cell lines at various concentrations (0, 10, 15, 25, 50, 75, 100) for 48 h using crystal violet binding assay. Results show that both the 7,8-diacetylated and 7,8-dihydroxylated 3-arylcoumarins showed cytotoxic activity against both cancer cell lines with CC50 (cytotoxic concentration 50) values at micro-molar levels, while the unsubstituted-3-arylcoumarins did not show cytotoxic activity. However, 3-(benzo[d] [1, 3] dioxol-5-yl)-2-oxo-2H-chromene-7, 8-diyldiacetate (47), 3-(naphthalen-1-yl)-2-oxo-2H-chromene-7, 8-diyldiacetate (51), and 3-(3, 5-dimethoxyphenyl)-7, 8-dihydroxy-2H-chromen-2-one (57) emerged as the most active compounds showing differential cytotoxicity in both cancer cell lines. For comparative studies, the cytotoxic activity of compounds 47, 51 and 57 was compared to a reference drug (Docetaxol (54)) in both cell lines. The results show that compounds activity is increased when acetoxy or hydroxyl groups is present at the C-7 and C-8 position, thus exhibiting the high cytotoxic activity. The differential cytotoxicity exhibited in both cancer cells was depended on the group substituted on the C-3 position, while compounds with H didn't show any significant cytotoxicity.
Furthermore, the most active compounds in each cancer cell line was evaluated for their in-vitro cytotoxic mechanism by analyzing their cytotoxic activity on cell cycle progression using flow cytometry, mitochondrial membrane potential (MMP) measurement (DeltaPsim) using Tetramethyl Rhodamine Methyl Ester (TMRM; Rhodamine-123) and reactive oxygen species (ROS) production using 2',7'-Dichlorofluorescin diacetate (DCFDA). 1. Cell cycle results from this investigation showed that compound (51) caused significant cell cycle arrest (p<0.01) at S and G2/M phases, while compound (57) caused significant cell cycle arrest (p<0.01) at G0/G1 phase in HepG2 (liver) cancer cell line. Additionally, compound (47) caused significant (p<0.01) at G0/G1 and S phases, while compound ( 57) significantly caused (p<0.01) at S and G2/M phases in A549 (lung) cancer cell line.
2. MMP/ROS result showed that compounds 47, 51, 57 caused significant loss of MMP after 24 and 48 h treatment in HepG2 (liver) and A549 (lung) cancer cells. An increase generation of ROS accumulation was also observed after treatment with compounds in each cancer cell line.
Overall, our study further confirms previous hypothesis that the nature of the substituent(s) and their pattern of substitution (e.g. 7,8-diacetoxy or 7,8-dihydroxyl group) on the core coumarin rings improved their cytotoxic activity in cancer cells, indicating that these compounds could serve as new leads for the development of novel synthetic anticancer drugs.
Notlar:
School code: 0872
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(687562.1) | 687562-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.