INSILICO DESIGN, SYNTHESIS AND CHARACTERIZATION OF SOME NOVEL BENZOTHIAZOLE DERIVATIVES AS ANTI-CANCER AGENTS
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i4.16407Abstract
Objectives: Cancer is a disease characterized by uncontrollable, irreversible, independent, autonomous, uncoordinated and relatively unlimited and abnormal over growth of tissues. Breast cancer is the second most common type of cancer after lung cancer. The aim of the study is to carry out the docking studies, synthesis and anti-tumour activities of Benzothiazole derivatives containing oxadiazole groups or amino groups.
Methods: The docking studies of benzothiazole derivatives were done with known anti-cancer targets like oestrogen receptor by using argus lab and auto dock programmes with the standard drug tamoxifen. Based upon  the results obtained from the molecular modeling, the derivatives were selected for the synthesis. The synthesized compounds were characterized by melting point, TLC, IR, 1H NMR, 13CNMR, MASS spectral data and screened for their in- vitro anti-cancer activities.
Results: The docking scores obtained for benzothiazole derivatives (BT1,BT2,BT3,BT4) and std.tamoxifen from the preliminary docking program by using  argusLab were- 9.68,
-9.4,-9.59, -11.1988,-9.71 and  by using autodock program were -6.29, -5.25,-7.19,-7.48,-3.86
 respectively. All the four derivatives were synthesized, characterized and subjected to in vitro anticancer screening by MTT assay in breast cancer (MCF-7) cell lines. Compounds DBT1, DBT2, DBT3 were the most active compounds against MCF-7 cell lines with IC50 of 70.0, 64.0 and 65.0, respectively.
Conclusion: All the four derivatives show good docking scores when compared to standard drug and can be concluded that all the synthesized benzothiazole ligands show good anti-cancer property.
Keywords: Benzothiazole, Oxadiazole, Estrogen receptor, Anticancer targets.
Downloads
References
Sukhbir L, Khokra M, Kanika A, Mehta H, Aggarwal A, Yadav M. Common Methods to synthesize benzothiazole derivatives and their medical significance. Int J Pharm Sci Res 2011;2(6):1356-77.
Weng JQ, Liu XH, Huang H, Tan CX, Chen J. Synthesis, structure and antifungal activity of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]benzo[d]thiazol-2(3H)-ones. Molecules 2012;17(1):989-1001.
Shanmukha I, Kumar MV, Jayachandran E, Revanasiddappa BC. Antiepileptic activity of some novel substituted fluoro benzothiazole derivatives. Int J Pharm Pharm Sci 2015;7(7):157-9.
Shi DF, Bradshaw TD, Wrigley S, McCall CJ, Lelieveld P, Fichtner I, et al. Antitumor benzothiazoles 3. Synthesis of 2-(4-aminophenyl) benzothiazoles and evaluation of their activities against breast cancer cell lines in vitro and in vivo. J Med Chem 1996;39(17):3375-84.
Venktesh P, Pandeya SN. Synthesis, characterization and anti-inflammatory activity of some 2-amino benzothiazole derivatives. Int J Chem Tech Res 2009;1(4):1354-8.
Pattan SR, Suresh CH, Pujar VD, Reddy VK, Rasal VP, Koti BC. Synthesis and anti-diabetic activity of 2-amino 5’ (4-sulphonylbenzylidine)-2,4-thiazolidinedione]-7-chloro-6-fluorobenzothiazole. Indian J Chem 2005;44(B):2404-8.
Mahfuz A, Nadeem S. Synthesis of new benzothiazole incorporated sulphonamides as potential anticonvulsants. Indian J Heterocycl Chem 2004;13(6):361-4.
Rajeeva B, Srinivasulu N, Shantakumar SM. Synthesis and antimicrobial activity of some new 2-substituted benzothiazole derivatives. EJ Chem 2009;6(2):775-9.
Yar MS, Ansari ZH. Synthesis and in vivo diuretic activity of biphenyl benzothiazole-2-carboxamide derivatives. Acta Pol Pharm Drug Res 2009;66(4):387-92.
Sunder S, Praveen S, Akash Y, Muttu CT, Ranjeeta V. Microwave assisted synthesis of fluoro, chloro, 2-N (substituted schiff’s bases)amino benzothiazoles as potential antimicrobial and antitubercular agents. Pharm Res 2009;1(4):345-56.
Mahran MA, William S, Ramzy F, Sembel AM. Synthesis and in vitro evaluation of new benzothiazole derivatives as schistosomicidal agents. Molecules 2007;12(5):622-33.
Sreenivasa GM, Jayachandran E, Shivakumar B, Jayaraj KK, Vijay K. Synthesis of bioactive molecule fluorobenzothiazole comprising potent heterocyclic moieties for anthelmentic activity. Arch Pharm Sci Res 2009;1(2):150-7.
Deepthy C, Leena KP, Manju P, Jinsha MJ, Jilsha G. In silico drug design and molecular docking studies of some novel benzothiazole derivatives as anti-cancer and anti-inflammatory agents. Int J Pharm Pharm Sci 2014;6(2):203-8.
Kubinyi H. QSAR and 3-D QSAR in drug design: 1. Methodology. Drug Discov Today 1997;2:457-67.
Thomas N, Zachariah SM. In silico drug design and analysis of 4-phenyl-4H-chromene derivatives as anticancer and anti-inflammatory agents. Int J Pharm Sci Rev Res 2013;22:50-4.
Hulka BS, Stark AT. Breast cancer: Cause and prevention. Lancet 1995;346(8979):883-7.
Bhattacharya J, Patel K, Tailor P, Karthikeyan C, Moorthy NS, Trivedi P. Design, synthesis and characterization of novel 1, 3, 4-oxadiazole dimers from benzoic acids. Int J ChemTech Res 2010;2(4):2055-62.
Amrutha BC. Priliminary phytochemical screening and cytotoxic activity of ethanolic extract of Ventilago madraspatana against human breast cancer. Int J Pharmacol Bio Sci 2011;5(2):75-8.
Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, et al. New colorimetric cytotoxic assay for anti-cancer drug screening. J Natl Cancer Inst 1990;82(13):1107-12.
Philip S. New colorimetric cytotoxic assay for anti-cancer drug screening J Nat Cancer Inst 1990;82:1107-12.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
