Synergistic Interactions of Atractylodes lancea Rhizome Compounds in the Treatment of Cholangiocarcinoma | Chapter 7 | Contemporary Research and Perspectives in Biological Science Vol. 3

 

Background: Cholangiocarcinoma (CCA)is the primary type of bile duct cancer with high morbidity and mortality, particularly in patients with advanced stages. Numerous studies have been carried out in efforts to discover effective cancer chemotherapeutic agents from plant sources with low toxicity. Treatment of CCA remains unsatisfactory due to the lack of sensitive and specific diagnostic tools for early detection and effective chemotherapeutics.

Purpose: The primary purpose of this study is to investigate cytotoxic interactions between the three major constituents of the rhizomes of Atractylodeslancea (Thunb)DC., i.e., β-eudesmol (BE), atractylodin (AT), and hinesol (HS) against CCA cell line. 

Methods: The bioactive constituents of AL rhizome under investigation, ie, BE, AT, HS, and 5-FU were purchased from Wako (Wako Ltd., Osaka, Japan). Cytotoxic activities against the human CCA cells CL-6 of the dual (BE:AT, BE:HS, and AT:HS) and triple (BE:AT:HS) combinations were evaluated using the assay. The cytotoxic interaction of each dual combination was assessed at five concentration ratios (10:0, 7:3, 5:5, 3:7, and 0:10) using isobologram analysis. The fractional inhibitory concentration index of each combination pair (representing combination scores) and the sum FIC of five distinctive ratios were calculated as the ratio of IC50 of the combination and that of each compound alone. For triple combination, the concentration ratio used in the experiment was 1:1.5:2.5(BE:AT:HS), and analysis of the interaction was performed using polygonogram analysis at the IC50 and IC90 concentrations (concentration that inhibits cell growth by 50% and 90%, respectively).

Results: The study was the first that confirmed the cytotoxic synergistic interaction of the three major compounds from AL rhizome on the human CCA cell line CL-6. The BE:AT combination produced the additive effect with a sum FIC (fractional inhibitory concentration) of 0.967±0.02 (mean±SD). The BE:HS and AT:HS combinations produced a synergistic effect with sum FICs of 0.685±0.08 and 0.767±0.09, respectively. The mixture of the three compounds produced synergistic interaction with CI (combination index) values of 0.519±0.10 and 0.65±0.17 (mean±SD) at the IC₅₀ and IC₉₀ concentration levels, respectively. 

Conclusion: The multi-ingredient characteristics of the plant extract would be expected to optimize therapy regarding both efficacy (synergistic anti-CCA activity) and tolerability (buffering effect). Results obtained would guide further development of AL as a potential anti-CCA chemotherapeutics concerning the appropriate pharmaceutical dosage form.

 

Author (s) Details

Pongsakorn Martviset
Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand and Faculty of Medical Technology, Rangsit University, Pathumthani 12000, Thailand.

 

Kesara Na-Bangchang
Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand, Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand and Drug Discovery and Development Center, Thammasat University, Pathumthani 12121, Thailand.

 

Please see the book here:- https://doi.org/10.9734/bpi/crpbs/v3/2408

Synthesis, Antibacterial and Cytotoxicity Assessment of Modified Uridine Molecules | Chapter 11 | Current Advances in Chemistry and Biochemistry Vol. 6

 Nucleoside derivatives continue to play an important role in the treatment of various diseases; therefore, in light of the importance of nucleoside analogues, we synthesized a series of nucleoside molecules, namely, uridine derivatives. The direct acylation of uridine molecules with N-acetylsulfanilyl chloride produced the corresponding 5-O-N-acetylsulfanilyluridine with ribose sugar moiety. The 5 -O-N-acetylsulfanilyluridine derivative was further transformed into a series of 2,3 -di-O-acyl derivatives containing a wide range of functionalities in a single molecular framework to produce newer products. The purity and structure of the products obtained have been confirmed. All uridine derivatives were tested in vitro for antibacterial activity against six human pathogenic bacterial strains. The study found that the selectively acylated derivatives 5 -O-Nacetylsulfanilyl-2,3 -di-O-lauroyluridine (7) and 5 -O-Nacetylsulfanilyl-2,3 -di-O-pivaloyluridine (10) inhibited Staphylococcus aureus and Bacillus cereus the best. Another interesting finding was that uridine derivatives were found to be more effective against Gram-positive bacteria than Gram-negative bacteria. Furthermore, the test compounds were tested for cytotoxicity using a brine shrimp lethality bioassay, and the compounds demonstrated varying rates of mortality at different concentrations. As a result, these synthesized derivatives have the potential to be used as antibacterial agents and are promising drug candidates for future therapeutic applications.

Author (s) Details

Asraful Alam
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

Md Anowar Hosen
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

Mariam Islam
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

Jannatul Ferdous
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

Yuki Fujii
Laboratory of Functional Morphology, Graduate School of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.

Yuki Fujii
Laboratory of Functional Morphology, Graduate School of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.

Sarkar M. A. Kawsar
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh

View Book :- https://stm.bookpi.org/CACB-V6/article/view/1443