Author(s):
Parthiban Brindha Devi, Shivanika Mani
Email(s):
pbrindhadevi@gmail.com
DOI:
10.5958/0974-360X.2021.00120.7 
Address:
Parthiban Brindha Devi*, Shivanika Mani
Department of Bio-Engineering, B. Tech Biotechnology, School of Engineering,
Vels Institute of Science, Technology and Advanced Studies, Pallavaram, Chennai-117
*Corresponding Author
Published In:
Volume - 14,
Issue - 2,
Year - 2021
ABSTRACT:
The hereditary unit of information, Deoxyribonucleic Acid (DNA) is present as compact structure chromatin, with the help of the histone and non-histone proteins. The equilibrium between the acetylation and deacetylation of the histone and non-histone proteins is essential for the regulation of the transcription and is controlled by the Histone Acetyltransferase (HAT) and Histone Deacteylase (HDAC) respectively. Imbalance of such leads to abnormal gene expression, even causing cancer development. HDAC activity is to remove the acetyl group, resulting hypoacetylation of histone protein, thus tightening the DNA wrapping around the nucleosomes, thereby decreasing the chances of Transcription factor binding. The aim of the study is to evaluate the drug likeliness and the determination of the action of secondary metabolites against the active site of the HDAC-2 by Insilco approach. It would be an initiative towards the development of opting natural compound as a lead for the treatment of disease caused due to the HDAC protein. In the present study, docking results discovered the binding of secondary metabolites with the Histone Deacetylase 2. Among those compounds, “Sphingosine 1-phosphate” and “oxamflatin” have binding energies greater than -11.88kCal/mol at the active site region of HDAC2 and gratify Lipinski’s rule, the basis for the lead to be used as an oral drug. Hence, it can be concluded that the secondary metabolites could be potent drugs for HDAC inhibitor
Cite this article:
Parthiban Brindha Devi, Shivanika Mani. A Promising Histone Deactelase Inhibitors from secondary metabolites-An In-silico Approach. Research J. Pharm. and Tech. 2021; 14(2):673-684. doi: 10.5958/0974-360X.2021.00120.7
Cite(Electronic):
Parthiban Brindha Devi, Shivanika Mani. A Promising Histone Deactelase Inhibitors from secondary metabolites-An In-silico Approach. Research J. Pharm. and Tech. 2021; 14(2):673-684. doi: 10.5958/0974-360X.2021.00120.7 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2021-14-2-16
REFERENCES:
1. Berger A, Venturelli S, Kallnischkies M, Böcker A, Busch C, Weiland T, Noor S, Leischner C, Weiss TS, Lauer UM, Bischoff SC. Kaempferol, a new nutrition-derived pan-inhibitor of human histone deacetylases. The Journal of Nutritional Biochemistry. 2013 Jun 1;24(6):977-85.
2. Bhalla KN. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. Journal of Clinical Oncology. 2005 Jun 10;23(17):3971-93.
3. Biçaku E, Marchion DC, Schmitt ML, Münster PN. Selective inhibition of histone deacetylase 2 silences progesterone receptor–mediated signaling. Cancer Research. 2008 Mar 1;68(5):1513-9.
4. Blander G, Guarente L. The Sir2 family of protein deacetylases. Annual Review of Biochemistry. 2004 Jul;73(1):417-35.
5. Crabb SJ, Howell M, Rogers H, Ishfaq M, Yurek-George A, Carey K, Pickering BM, East P, Mitter R, Maeda S, Johnson PW. Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin A. Biochemical Pharmacology. 2008 Aug 15;76(4):463-75.
6. Farooqi AA, Naqvi SK, Perk AA, Yanar O, Tabassum S, Ahmad MS, Mansoor Q, Ashry MS, Ismail M, Naoum GE, Arafat WO. Natural agents-mediated targeting of histone deacetylases. Archivum Immunologiae Et Therapiae Experimentalis. 2018 Feb 1;66(1):31-44.
7. Ghosh AK, Kulkarni S. Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylase. Organic Letters. 2008 Jul 29;10(17):3907-9.
8. Ha MK, Song YH, Jeong SJ, Lee HJ, Jung JH, Kim B, Song HS, Huh JE, Kim SH. Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1 in hypoxic rheumatoid synoviocytes. Biological and Pharmaceutical Bulletin. 2011 Sep 1;34(9):1432-7.
9. Hait NC, Allegood J, Maceyka M, Strub GM, Harikumar KB, Singh SK, Luo C, Marmorstein R, Kordula T, Milstien S, Spiegel S. Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science. 2009 Sep 4;325(5945):1254-7.
10. Harms KL, Chen X. Histone deacetylase 2 modulates p53 transcriptional activities through regulation of p53-DNA binding activity. Cancer Research. 2007 Apr 1;67(7):3145-52.
11. Hassig CA, Schreiber SL. Nuclear histone acetylases and deacetylases and transcriptional regulation: HATs off to HDACs. Current Opinion in Chemical Biology. 1997 Oct 1;1(3):300-8.
12. Huang BH, Laban M, Leung CH, Lee L, Lee CK, Salto-Tellez M, Raju GC, Hooi SC. Inhibition of histone deacetylase 2 increases apoptosis and p21 Cip1/WAF1 expression, independent of histone deacetylase 1. Cell Death and Differentiation. 2005 Apr;12(4):395.
13. Inoue S, Mai A, Dyer MJ, Cohen GM. Inhibition of histone deacetylase class I but not class II is critical for the sensitization of leukemic cells to tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis. Cancer research. 2006 Jul 1;66(13): 6785-92.
14. Jaibu AE, Sundaram RS, Krishnaveni K, Sambathkumar R. Targeted Cancer Therapy: Promises and Reality. Research Journal of Pharmacy and Technology. 2018;11(4):1407-12.
15. Jung M, Hoffmann K, Brosch G, Loidl P. Analogues of trichosтatin a and trapoxin B as histone deacetylase inhibitors. Bioorganic and Medicinal Chemistry Letters. 1997 Jul 8;7(13): 1655-8.
16. Kaur N, Singh K. 3D-QSAR and Molecular Docking Studies of N-(2-Aminophenyl)-Benzamide Derivatives as Inhibitors of HDAC2. Research Journal of Pharmacy and Technology. 2014;7(7):760-70.
17. Kedar MS, Shirbhate MP, Chauhan R, Sharma S, Verma A. Design Synthesis and Evaluation of Anticancer Pyrazole Derivatives of Chalcone Scaffold. Research Journal of Pharmacy and Technology. 2020;13(1):342-6.
18. Kim H, Kim SN, Park YS, Kim NH, Han JW, Lee HY, Kim YK. HDAC inhibitors downregulate MRP2 expression in multidrug resistant cancer cells: implication for chemosensitization. International Journal of Oncology. 2011 Mar 1;38(3): 807-12.
19. Kim YB, Lee KH, Sugita K, Yoshida M, Horinouchi S. Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase. Oncogene. 1999 Apr; 18(15): 2461.
20. Kwon, Ho Jeong, et al. "Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase." Proceedings of the National Academy of Sciences 95.7 (1998): 3356-3361.
21. Kyrylenko S, Kyrylenko O, Suuronen T, Salminen A. Differential regulation of the Sir2 histone deacetylase gene family by inhibitors of class I and II histone deacetylases. Cellular and Molecular Life Sciences CMLS. 2003 Sep 1;60(9):1990-7.
22. Lehrmann H, Pritchard LL, Harel-Bellan A. Histone acetyltransferases and deacetylases in the control of cell proliferation and differentiation.
23. Li Y, Li X, Guo B. Chemopreventive agent 3, 3′-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. Cancer Research. 2010 Jan 15;70(2):646-54.
24. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 1997 Jan 15;23(1-3):3-25.
25. Nandan BL, Sequeira VM, Verma K, Ramanathan K. Exploring beta-tubulin-protein interactome using computational techniques. Research Journal of Pharmacy and Technology. 2015;8(12):1679-84.
26. Nayak SK, Khatik GL, Narang R, Monga V. Role of Mdm2 Cascade in Human Cancers. Research Journal of Pharmacy and Technology. 2017;10(7):2236-42.
27. Nishino N, Jose B, Shinta R, Kato T, Komatsu Y, Yoshida M. Chlamydocin–hydroxamic acid analogues as histone deacetylase inhibitors. Bioorganic and Medicinal Chemistry. 2004 Nov 15;12(22):5777-84.
28. Oehme I, Deubzer HE, Wegener D, Pickert D, Linke JP, Hero B, Kopp-Schneider A, Westermann F, Ulrich SM, von Deimling A, Fischer M. Histone deacetylase 8 in neuroblastoma tumorigenesis. Clinical Cancer Research. 2009 Jan 1;15(1):91-9.
29. Ononye SN, VanHeyst MD, Oblak EZ, Zhou W, Ammar M, Anderson AC, Wright DL. Tropolones as lead-like natural products: the development of potent and selective histone deacetylase inhibitors. ACS Medicinal Chemistry Letters. 2013 Jun 11;4(8):757-61.
30. Orlikova B, Schnekenburger M, Zloh M, Golais F, Diederich M, Tasdemir D. Natural chalcones as dual inhibitors of HDACs and NF-κB. Oncology reports. 2012 Sep 1;28(3):797-805.
31. Pal-Bhadra M, Ramaiah MJ, Reddy TL, Krishnan A, Pushpavalli SN, Babu KS, Tiwari AK, Rao JM, Yadav JS, Bhadra U. Plant HDAC inhibitor chrysin arrest cell growth and induce p21 WAF1 by altering chromatin of STAT response element in A375 cells. BMC Cancer. 2012 Dec;12(1):180.
32. Pandey M, Kaur P, Shukla S, Abbas A, Fu P, Gupta S. Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: in vitro and in vivo study. Molecular carcinogenesis. 2012 Dec; 51(12): 952-62.
33. Park SY, Kim KB, Ahn SH, Kim HH. Antidepressive effects of Gami-Shinkiwhanin immobilization stressed aging mice. Research Journal of Pharmacy and Technology. 2018;11(5):1909-16.
34. Phillip CJ, Giardina CK, Bilir B, Cutler DJ, Lai YH, Kucuk O, Moreno CS. Genistein cooperates with the histone deacetylase inhibitor vorinostat to induce cell death in prostate cancer cells. BMC Cancer. 2012 Dec;12(1):145.
35. Ravi A, Raj MG, Arunachalam S, Sathiavelu M. Marine environment: A potential source for anticancer drugs. Research Journal of Pharmacy and Technology. 2017;10(5):1543-50.
36. Ropero S, Fraga MF, Ballestar E, Hamelin R, Yamamoto H, Boix-Chornet M, Caballero R, Alaminos M, Setien F, Paz MF, Herranz M. A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Nature Genetics. 2006 May;38(5):566.
37. Saha D, Maity T, Jana M, Mandal S. Cancer treatment strategy-an overview. Asian Journal of Pharmacy and Technology. 2011; 1(2): 28-33.
38. Saijo K, Katoh T, Shimodaira H, Oda A, Takahashi O, Ishioka C. Romidepsin (FK 228) and its analogs directly inhibit phosphatidylinositol 3‐kinase activity and potently induce apoptosis as histone deacetylase/phosphatidylinositol 3‐kinase dual inhibitors. Cancer Science. 2012 Nov;103(11):1994-2001.
39. Salminen A, Tapiola T, Korhonen P, Suuronen T. Neuronal apoptosis induced by histone deacetylase inhibitors. Molecular Brain Research. 1998 Oct 30;61(1-2):203-6.
40. Soflaei SS, Momtazi-Borojeni AA, Majeed M, Derosa G, Maffioli P, Sahebkar A. Curcumin: a natural pan-HDAC inhibitor in cancer. Current Pharmaceutical Design. 2018 Jan 1;24(2):123-9.
41. Son IH, Chung IM, Lee SI, Yang HD, Moon HI. Pomiferin, histone deacetylase inhibitor isolated from the fruits of Maclura pomifera. Bioorganic and Medicinal Chemistry Letters. 2007 Sep 1;17(17):4753-5.
42. Sun LP, Chen AL, Hung HC, Chien YH, Huang JS, Huang CY, Chen YW, Chen CN. Chrysin: a histone deacetylase 8 inhibitor with anticancer activity and a suitable candidate for the standardization of Chinese propolis. Journal of Agricultural and Food Chemistry. 2012 Nov 15;60(47):11748-58.
43. Upadhyay A, Mishra A, Chaudhury S, Chattopadhyay P. Mitochondrial Anti-Oxidant Enzymes Caused by Cigarette Smoke in Experimental Wistar Rat. Research Journal of Pharmacy and Technology. 2009;2(4):690-3.
44. Varghese TA, Jayasri MA, Suthindhiran K. Marine A ctinomycetes as potential source for histone deacetylase inhibitors and epigenetic modulation. Letters in applied microbiology. 2015 Jul; 61(1): 69-76.
45. Venkatachalam S, Jaiswal A, De A, Vijayakumar RK. Repurposing Drugs for Management of Alzheimer Disease. Research Journal of Pharmacy and Technology. 2019 Jun 1;12(6): 3078-88.
46. Vickers CJ, Olsen CA, Leman LJ, Ghadiri MR. Discovery of HDAC inhibitors that lack an active site Zn2+-binding functional group. ACS Medicinal Chemistry Letters. 2012 Apr 30;3(6):505-8.
47. Yoshida M, Horinouchi S. Trichostatin and Leptomycin: Inhibition of Histone Deacetylation and Signal‐Dependent Nuclear Export. Annals of the New York Academy of Sciences. 1999 Dec;886(1):23-35.