MOLECULAR DOCKING STUDY, SYNTHESIS AND INVI-TRO EVALUATION OF ANTITUMOR ACTIVITY OF NOVEL NAPHTHYLIDENE BASE OF BENZOIC ACID DERIVATIVES
Keywords:In vitro anticancer, Histone deacetylase 8, synthesis, Molecular Docking
Cancer therapies targeted developing cell cycle-based mechanism that emulates the body’s natural process in order to stop the growth of cancer cells. This approach can limit the damage to normal cells and the accompanying side effects caused by conventional chemotherapeutic agents. Inhibition of histone deacetylase (HDAC) enzymes is emerging as an innovative and effective approach for the treatment of cancer. Nineteen compounds of naphthylidene base of benzoic acid derivatives were designed and tested in silico for their interaction with histone deacetylase (HDAC8) enzyme. 19 ligands docked with Histone deacetylase 8 Human HDAC8 (PDB ID: 1T69) using Glide program (Version 5.0, Schrodinger, LLC, New York, 2008) and designed, synthesized and evaluated for their ability to inhibit cell proliferation in cancer cell lines. Based on the docking score 4-((2-hydroxynaphthalen-1-yl)methyleneamino) benzoic acid showed highest docking score of -5.8214, which is important for HDAC8 inhibition. In this present investigation, molecular docking, design, synthesize and evaluated for in vitro antitumor activity to identify novel active compound targeting the HDAC8 protein. Among the 19 compounds A19 showed promising activity against human cervical cancer cell line.
Monneret C., Histone deacetylase inhibitors. Eur J Med Chem, 40: 1–13, 2005.
Kouzarides T., Histone acetylases and deacetylases in cell proliferation. Curr Opin Genet Dev. 9: 40-8, 1999.
Naresh K., Geetha Ramakrishnan V., Sarma Jagarlapudi S., QSAR Studies of N-(2-Aminophenyl)- Benzamide derivatives as Histone deacetylase2 Inhibitors. Int J PharmTech Res. 4: 1110-1121, 2012.
Ioakimidis L., Loizos T., Amin M., Saira N., Johannes R., Benchmarking the reliability of QikProp. Correlation between experimental and predicted values. QSAR & Comb Sci. 27(4): 445-456, 2008.
Wang W., Yuqing Z., Elizabeth RR., Donald LH., Hui W., Ruiwen Z., In vitro anti-cancer activity and structure–activity relationships of natural products isolated from fruits of Panax ginseng. Cancer Chemother Pharmacol. 59(5): 589-601, 2007.
Boyd MR., Paull KD., Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res. 34: 91-109, 1995.
Tamm I., Yan Wang ED., Sausville DA., Scudiero NV., Tilman O., John CR., IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 58(23): 5315-5320, 1998.
Johnson JI., Decker S., Zaharevitz D., Rubinstein LV., Venditti JM., Schepartz S., Kalyandrug S., Christian M., Arbuck S., Hollingshead M., Sausville EA., Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 84(10): 1424, 2001.
Shoemaker M., Bobbi Hamilton SH., Dairkee IC., Michael JC., In vitro anticancer activity of twelve Chinese medicinal herbs. Phytotherapy Res. 19(7): 649-651, 2005.
Kelter G., Nigel JS., Katja S., Heinz Herbert F., Matthias T., In-vitro anti-tumor activity studies of bridged and unbridged benzyl-substituted titanocenes. Anti-Cancer Drugs. 16(10): 1091-1098, 2005.
Seeram NP., Lynn SA., Susanne MH., Yantao N., Yanjun Z., Muraleedharan GN., David H., In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 16(6): 360-367, 2005.
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