SYNTHESIS AND ANTICANCER SCREENING OF TRIAZINE ANALOGUES
Keywords:Cancer, Triazine Analogues, MCF-7, K-562, Anticancer activity, EGFR
Objective: The study was aimed to investigate the cytotoxic effect of S-5H-[1,2,4]-triazino (5,6-b) indol-3-yl-3,4-phenylethane-thioate derivatives as epidermal growth factor Receptor (EGFR) inhibitors.
Methods: In the present study 14 novel triazine analogues were synthesized and characterized using different spectroscopic techniques such as FT-IR, NMR and Mass Spectroscopy. The anticancer activity was performed using MCF-7 (breast cancer) and K-562 (leukaemia) cell lines. Further, molecular docking was carried out using Vlife Molecular Docking Software (MDS) on crystal structure of epidermal growth factor receptor (EGFR) to identify the binding mode of interaction with an active site.
Results: Compounds MA-7, MA-8, MA-12, MA-13 and MA-14 show potent activity against cancer cell lines in the range of<10 to 84.4 µg/ml. Further molecular docking on EGFR also supports that there is a strong correlation between in silico and in vitro biological activity. The results of this study may be further useful for lead optimization process.
Conclusion: The results of this study indicates that the synthesized triazine analogues can give a potential lead as an anticancer agent.
Subrahmanyam V, Vanita P, Jhansi K. A short note on cancer. J Carcinog Mutagen 2011;2:128.
McBee Jr WC, Gardiner AS, Edwards RP, Lesnock JL, Bhargava R. MicroRNA analysis in human papillomavirus (HPV)-associated cervical neoplasia and cancer. J Carcinog Mutagen 2000;1. ), Pune for mass providing LC/MS services.
Augustin HG. Antiangiogenic tumour therapy: will it work? Trends Pharm Sci 1998;19:216-22.
Hinck L, Näthke I. Changes in cell and tissue organization in cancer of the breast and colon. Curr Opi Cell Bio 2000;26:87-95.
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99.
Racil Z, Razga F, Drapalova J, Buresova L, Zackova D, Palackova M, et al. Mechanism of impaired glucose metabolism during nilotinib therapy in patients with chronic myelogenous leukemia. Haematol Haematol 2013;98:e124-6.
Sharma GN, Dave R, Sanadya J, Sharma P, Sharma KK. Various types and management of breast cancer: an overview. J Adv Pharm Tech Res 2010;1:109.
Perou, Charles M, Therese Sørlie, Michael B Eisen, Matt Van De Rijn, Stefanie S Jeffrey, Christian A Rees, et al. Molecular portraits of human breast tumours. Nature 2000;406:747.
Hallek M, Cheson BD, Catovsky D, Caligaris Cappio F, Dighiero G, Dohner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the international workshop on chronic lymphocytic leukemia updating the national cancer institute–working group 1996 guidelines. Blood 2008;111:5446-56.
Else M, Ruchlemer R, Osuji N, Del Giudice I, Matutes E, Woodman A, et al. Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow‐up of 12.5 y. Cancer Interdisciplinary Int J Am Soc 2005;104:2442-8.
Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, et al. A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Can Res 2004;64:6652-9.
Campbell P, Morton PE, Takeichi T, Salam A, Roberts N, Proudfoot LE, et al. Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR. J Inves Derm 2014;134:2570-8.
Yun UJ, Sung JY, Park SY, Ye SK, Shim J, Lee JS, et al. Oncogenic role of rab escort protein 1 through EGFR and STAT3 pathway. Cell Death Dis 2017;8:e2621.
Zwick E, Hackel PO, Prenzel N, Ullrich A. The EGF receptor as central transducer of heterologous signalling systems. Trends Pharm Sci 1999;20:408-12.
Aswar UM, Kalshetti PP, Shelke SM, Bhosale SH, Bodhankar SL. Effect of newly synthesized 1, 2, 4-triazino [5, 6-b] indole-3-thione derivatives on olfactory bulbectomy induced depression in rats. Asi Pac J Trop Biomed 2012;2:992-8.
Babu TMC, Rajesh SS, Bhaskar BV, Devi S, Rammohan A, Sivaraman T, et al. Molecular docking, molecular dynamics simulation, biological evaluation and 2D QSAR analysis of flavonoids from syzygium alternifolium as potent anti-helicobacter pylori agents. RSC Adv 2017;7:18277-92.
Noolvi MN, Patel HM. A comparative QSAR analysis and molecular docking studies of quinazoline derivatives as tyrosine kinase (EGFR) inhibitors: A rational approach to anticancer drug design. J Saudi Chem Soc 2013;17:361-79.
Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 2006;1:1112.
Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. JNCI: J Nat Can Ins 1990;82:1107-12.
Variya B, Modi S, Savjani J, Patel S. In silico molecular docking and pharmacokinetic prediction of gallic acid derivatives as PPAR-γ agonists. Int J Pharm Pharml Sci 2017;9:102-7.
Shinde MG, Modi SJ, Kulkarni VM. Synthesis, pharmacological evaluation, molecular docking and in silico ADMET prediction of nitric oxide releasing biphenyls as anti-inflammatory agents. J Appl Pharm Sci 2017;7:37-47.