MOLECULAR DOCKING STUDIES OF OPENED-CHAIN ANALOGUES OF ANTIMYCIN A ASCASPASES INHIBITORS OF APOPTOSIS IN COLORECTAL CANCER 3

Authors

  • Fadilah Fadilah University of Indonesia
  • Ade Arsianti
  • Kusmardi Kusmardi
  • Aryo Tedjo

Abstract

Objective: Studies of open-chain analogues of antimycin A
as caspase inhibitors of apoptosis by molecular docking approach through computeraided
drug design. The novelty
of this study
is finding the potential
antimycin
A
3
3
analogues which structurally modified against caspases.
Methods: In finding potential caspase inhibitor of apoptosis in colorectal cancer (CRC) by in silico approach has been utilized. Protein structure of
caspase has been downloaded from Protein Data Bank (1SHJ). The minimized of caspase was ready for molecular docking analysis. Analogues of
antimycin A
as lead compounds were designed and assessed using Molsoft drug-likeness. Both protein and lignan derivatives were docked with
Autodock 4.2. The best docking score was shown by the lowest binding energy.
3
Results: Analogues of antimycin A
has been done by evaluating their physicochemical properties as lead compounds. From this assessment, it
showed that analogue 2 (AMD2), intermediate amide 4 (AMD4) showed good compounds to be drug-likeness by following Lipinski's rule of five
(RO5), while intermediate amide 3 (AMD3) and antimycin A
3
(AMY3) showed cannot followed in Lipinski's RO5. From molecular docking result, the
most favorable binding of caspase was AMD4 and AMD2 based on its energy that AMD4 (−7.34 kcal/mol) has the best binding interaction compared
to AMD2 (−7.33 kcal/mol), AMY3 (−7.26 kcal/mol), and AMD3 (−5.23 kcal/mol), respectively.
3
Conclusion: This studies demonstrated that the opened-chain analogues of antimycin A
AMD2 and AMD4 as a promising candidates of caspase
inhibitor of apoptosis in CRC.
Keywords: Open-chain analogue, Antimycin A
3
, Caspase, Apoptosis, Anticolorectal cancer.
3,

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References

Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA

Cancer J Clin 2014;64(2):104-17.

Watson AJ. Apoptosis and colorectal cancer. Recent Adv Basic Sci

;53:1701-9.

Ueki M, Kusumoto A, Hanafi M, Shibata K, Tanaka T, Taniguchi M.

UK-3A, a novel antifungal antibiotic from Streptomyces sp 517-02:

Fermentation, isolation, structural elucidation and biological properties.

J Antibiot (Tokyo) 1997;50(7):551-5.

Miyoshi H, Tokutake N, Imaeda Y, Akagi T, Iwamura H. A model

of antimycin A binding based on structure-activity studies

of synthetic antimycin A analogues. Biochim Biophys Acta

;1229(2):149-54.

Arsianti A, Fadilah F, Kusmardi K, Tanimoto H, Kakiuchi K. Design,

synthesis and cytotoxicity of novel opened chain analogues of

antimycin A3 as potential anticolorectal cancer agents. Asian J Pharm

Clin Res 2015;8(6):120-4.

Jonges LE, Nagelkerke JF, Ensink NG, van der Velde EA, Tollenaar RA,

Fleuren GJ, et al. Caspase-3 activity as a prognostic factor in colorectal

carcinoma. Lab Invest 2001;81(5):681-8.

de Heer P, de Bruin EC, Klein-Kranenbarg E, Aalbers RI, Marijnen CA,

Putter H, et al. Caspase-3 activity predicts local recurrence in rectal

cancer. Clin Cancer Res 2007;13(19):5810-5.

Nogara PA, Saraiva Rde A, Caeran Bueno D, Lissner LJ, Lenz Dalla

Corte C, Braga MM, et al. Virtual screening of acetylcholinesterase

inhibitors using the lipinski’s rule of five and ZINC databank. Biomed

Res Int 2015;2015:870389.

Sanner MF. Python: A programming language for software integration

and development. J Mol Graph Model 1999;17(1):57-61.

Southan C, Stracz A. Extracting and connecting chemical structures

from text sources using chemicalize.org. J Cheminform 2013;5(1):20.

MarvinSketch. Available from: http://www.chemaxon.com/marvin/

sketch/index.jsp.

Fernandez-Recio J, Totrov M, Abagyan R. Screened charge electrostatic

model in protein-protein docking simulations. Pac Symp Biocomput

:552-63.

Norgan AP, Coffman PK, Kocher JP, Katzmann DJ, Sosa CP. Multilevel

parallelization of autodock 4.2. J Cheminform 2011;3(1):12.

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM,

Meng EC, et al. UCSF chimera: A visualization system for exploratory

research and analysis. J Comput Chem 2004;25(13):1605-12.

Martel S, Gillerat F, Carosati E, Maiarelli D, Tetko IV, Mannhold R,

et al. Large, chemically diverse dataset of logP measurements for

benchmarking studies. Eur J Pharm Sci 2013;48(1-2):21-9.

Korinth G, Wellner T, Schaller KH, Drexler H. Potential of the

octanol-water partition coefficient (logP) to predict the dermal

penetration behaviour of amphiphilic compounds in aqueous solutions.

Toxicol Lett 2012;215(1):49-53.

Published

01-05-2016

How to Cite

Fadilah, F., A. Arsianti, K. Kusmardi, and A. Tedjo. “MOLECULAR DOCKING STUDIES OF OPENED-CHAIN ANALOGUES OF ANTIMYCIN A ASCASPASES INHIBITORS OF APOPTOSIS IN COLORECTAL CANCER 3”. Asian Journal of Pharmaceutical and Clinical Research, vol. 9, no. 3, May 2016, pp. 350-2, https://mail.innovareacademics.in/journals/index.php/ajpcr/article/view/11485.

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