ANTI CANCER STUDIES OF SELECTIVE MANNICH BASES BY IN SILICO METHOD
Objective: To evaluate the anticancer activities of selective Mannich bases by in silico methods.
Methods: X-ray crystallographic structure of Estrogen receptor protein (PDB ID 2YAT) was downloaded from the protein data bank (PDB) and is docked with the target Mannich bases using Accelyrs Discovery Studio client version 2.5 software.
Results: Based on the in silico analysis results of the target compounds with standard drug tamoxifen, the best-docked compound is identified and its anticancer activity is confirmed by using in vitro MTS analysis using Raju and Jurkat cell lines.
Conclusion: The mannich base compound N-[(Diphenylamino) methyl] acetamide showed fourfold higher activity than standard drug tamoxifen, may be used to overcome the drug resistance of Estrogen receptor protein.
2. Guoshun Luo, Mingqi Chen, Weiting Lyu, Ruheng Zhao, Hua Xiang. Design, synthesis, biological evaluation and molecular docking studies of novel 3-aryl-4-anilino-2H-chromen-2-one derivatives targeting ERÎ± as anti-breasr cancer agents. Bioinorg Med Chem Lett 2017;27:2668-73.
3. Venumadhav Janganati, Jessica Ponder, Shraddha Thakkar, Craig T Jordan, Peter A Crooks. Succinamide derivatives of melampomagnolide B and their anti-cancer activities. Bioinorg Med Chem 2017;25:3694-705.
4. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 2001;46:3-26.
5. K Meenakshi, N Gopal, M Sarangapani. Synthesis, characterization and antimicrobial activity of some novel schiff and mannich bases of isatin. Int J Pharm Pharm Sci 2014;6:318-22.
6. Pandeya SN, Lakshmi VS, Pandey A. Biological activity of mannich bases. Indian J Pharm Sci 2003;65:213-22.
7. Gheorghe Roman. Mannich bases in medicinal chemistry and drug design. Eur J Med Chem 2015;89:743-816.
8. Suman Bala, Neha Sharma, Anu Kajal, Sunil Kamboj, Vipin Saini. Mannich bases: an important pharmacophore in the present scenario. Intl J Med Chem 2014. http://dx.doi.org/ 10.1155/ 2014/191072.
9. Jeyabaskar Suganya, Mahendran Radha, Devi Leimarembi Naorem, Marimuthu Nishandhini. In silico docking studies of selected flavonoids-natural healing agents against breast cancer. Asian Pac J Cancer Prev 2014;15:8155-9.
10. Alpha Kumaraswamy Naidu Chitrala, Suneetha Yeguvapalli. Prediction and analysis of ligands for estrogen-related receptor. Asian Pac J Cancer Prev 2013;14:2371-5.
11. Pete Donnell, Murad Banaji, Anca Marginean, Casian Pantea. CoNtRol: an open source framework for the analysis of chemical reaction networks. Bioinformatics 2014;30:1633-4.
12. Benson JR, Jatoi I. The global breast cancer burden. Future Oncol 2012;8:697-702.
13. Fuqua SA. The role of estrogen receptors in breast cancer metastasis. J Mammary Gland Biol Neoplasia 2001;6:407-17.
14. Izadi P, Noruzinia M, Fereidooni F, Nateghi MR. Association of poor prognosis subtypes of breast cancer with estrogen receptor alpha methylation in Iranian women. Asian Pac J Cancer Prev 2012;13:4113-7.
15. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 2001;46:3-26.
16. Idhayadhulla A, Surendra Kumar R, Jamal Abdul Nasser A, Selvin J, Aseer Manilal. Synthesis of some mannich base derivetives derivatives and their antimicrobial activity study. Arabian J Chem 2014;7:994-9.
17. Yan Li, Xiaoming Qiang, Li Luo, Xia Yang, Yong Deng Aurone. Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-Î²-amyloid aggregation and neuroprotective properties for the treatment of Alzheimer's disease. Eur J Med Chem 2017;126:762-75.
18. Mona Piplani, Harish Rajak, Prabodh Chander Sharma. Synthesis and characterization of N-Mannich based prodrugs of ciprofloxacin and norfloxacin: In vitro anthelmintic and cytotoxic evaluation. J Adv Res 2017;8:463-70.