Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In Vitro Biological Estimation of 1,2,3-Triazolo[4,5-d]pyrimidine Derivatives as Anti-breast Cancer Agent: DFT, QSAR and Docking Studies

Author(s): Oyebamiji A. Kolawole and Semire Banjo*

Volume 21, Issue 1, 2020

Page: [70 - 78] Pages: 9

DOI: 10.2174/1389201020666190904163003

Price: $65

Abstract

Background & Objective: Series of synthesized molecular compounds were considered as anti-breast cancer. The molecular descriptors which describe the microbial activities of the studied compounds were calculated using theoretical approach.

Methods: The calculated parameters obtained EHOMO (eV), ELUMO (eV), dipole moment (Debye), log P, molecular weight (amu), HBA, HBD, Vol and Ovality were screened. The obtained calculated descriptors were used to develop QSAR model for prediction of experimental inhibition concentration (IC50) using SPSS and Gretl software packages for multiple linear regression (MLR) and MATLAB for the artificial neural network (ANN).

Results: From this statistical analysis, MLR and ANN were observed to be predictive, however, ANNQSAR model predicted more efficiently than MLR.

Conclusion: Furthermore, molecular docking study was executed with breast cancer cell line (PDB ID: 1hi7); it was observed that BS20 with binding energy of -7.0 kcal/mol bounded more efficiently than other compounds also, it inhibited more than the standard used (5-FU).

Keywords: 1, 2, 3-triazolo[4, 5-d]pyrimidine analogues, triazole, pyrimidine, DFT, QSAR, docking.

« Previous Next »
Graphical Abstract

[1]
Rana, N.; Nagham, M.A.; Majid, J. Synthesis, identification of heterocyclic compounds and study of biological activity. Asian J. Res. Chem, 2014, 7(7), 664-676.
[2]
Clayden, G. Warren and Wothers, Organic Chemistry, 1st ed; Oxford University: New York, 2001.
[3]
Theophil, E. Siegfried, Hanpt, M. The Chemistry of Hetero cycles, 2th Ed.; Wiley, VCH, 2003.
[4]
Joule, J.A.; Mills, K. Hetero Cyclic Chemistry, 5th ed; Wiley & Sons LTD: U.K, 2010.
[5]
Louis, D.Q.; John, A.T. Fundamentals of Hetero Cyclic Chemistry, 9th ed; Wiley: New York, 2010.
[6]
Paula, Y.B. Organic Chemistry; 6th Ed., United State of America, 34
[7]
Mohammed, I.A.; Mustapha, A. Synthesis of new azo compounds based on N-(4-hydroxypheneyl)maleimide and N-(4-methylpheneyl)maleimide. Molecules, 2010, 15(10), 7498-7509.
[http://dx.doi.org/10.3390/molecules15107498] [PMID: 20975631]
[8]
Pradnya, R.G.; Sanjay, P.W.; Ashok, P.M.; Kishor, P.B.; Nitin, B.C. Synthesis and antimicrobial activities of 1-Naphthylamine based acetophenone semicarbazones. Med. Chem. Drug Discov., 2012, 3(1), 11-19.
[9]
Wu, J.; Hu, L.; Du, Y.; Kong, F.; Pan, Y. Prognostic role of LSD1 in various cancers: Evidence from a meta-analysis. OncoTargets Ther., 2015, 8, 2565-2570.
[10]
Miles, W.O. Lepesant. J.M.; Bourdeaux. J.; Texier, M.; Kerenyi, M.A.; Nakakido, M.; Hamamoto, R.; Orkin, S.H.; Dyson, N.J.; Di Stefano, L. The LSD1 family of histone demethylases and the pumilio posttranscriptional repressor function in a complex regulatory feedback loop. Mol. Cell. Biol., 2015, 35, e4199-e4211.
[11]
Gupta, R.; Gupta, A.K.; Paul, S. 1,3,4-Oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid: Synthesis and preliminary evaluation of biological properties. Indian J. Chem. Sect. B, 2000, 39, 847.
[12]
El Wassimy, M.T.M.; Abdel-Rahman, M.; Ghattas, A.B.A.G.; Abdallah, O.A.A. Synthesis and reactions of n-chloromethyl-1,2,4-triazoles with sulfur and oxygen nucleophiles. Phosphorus Sulfur Silicon Relat. Elem., 1992, 70, 99-108.
[http://dx.doi.org/10.1080/10426509208049156]
[13]
Basu, N.K.; Rose, F.L. S-triazolopyridazines: Synthesis as potential therapeutic agents. J. Chem. Soc., 1963, 5660.
[http://dx.doi.org/10.1039/jr9630005660]
[14]
El-Dawy, M.A.; Omar, A.M.; Ismail, A.M.; Hazzaa, A.A. Potential broad spectrum anthelmintics IV: design, synthesis, and antiparasitic screening of certain 3,6-disubstituted-(7H)-s-triazolo-[3,4-b][1,3,4]thiadiazine derivatives. J. Pharm. Sci., 1983, 72(1), 45-50.
[http://dx.doi.org/10.1002/jps.2600720111] [PMID: 6827463]
[15]
Mishra, A.; Srivastava, K.; Tripathi, R.; Puri, S.K.; Batra, S. Search for new pharmacophores for antimalarial activity., Part III: Synthesis and bioevaluation of new 6-thioureido-4-anilinoquinazolines Eur. J. Med. Chem., 2009, 44, 4404e4412.
[16]
Lazrak, F.; Essassi, E.M.; Kandri Rodi, Y.; Misbahi, K.; Pierrot, M. Synthese de nouveaux systemes condenses renfermant Le 1,2,4-triazole, la 1,3-thiazine, la 1,3-thiazepine et la 1,3,5,7-dithiadiazocine. Phosphorus Sulfur Silicon Relat. Elem., 1792, 4, 1799-1808.
[17]
Lazrak, F.; Ahabchane, N.H.; Keita, A.; Essassi, E.M.; Pierrot, M. Synthesis and crystal structure of 3-methoxycarbonyl-5-methyl-1-p-tolyl-1,2,4-triazolo [3,4-c]-1,2,4-triazole. Indian J. Chem. Section B Org. Med. Chem., 2002, 41(4), 821-825.
[http://dx.doi.org/10.1002/chin.200233143]
[18]
Song, M.X.; Deng, X.Q. Recent developments on triazole nucleus in anticonvulsant compounds: A review. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 453-478.
[http://dx.doi.org/10.1080/14756366.2017.1423068] [PMID: 29383949]
[19]
Ma, L.Y.; Pang, L.P.; Wang, B.; Zhang, M.; Hu, B.; Xue, D.Q.; Shao, K.P.; Zhang, B.L.; Liu, Y.; Zhang, E.; Liu, H.M. Design and synthesis of novel 1,2,3-triazole-pyrimidine hybrids as potential anticancer agents. Eur. J. Med. Chem., 2014, 86, 368-380.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.010] [PMID: 25180925]
[20]
Mavrova, A.Ts.; Wesselinova, D.; Tsenov, J.A.; Lubenov, L.A. Synthesis and antiproliferative activity of some new thieno[2,3-d]pyrimidin-4(3H)-ones containing 1,2,4-triazole and 1,3,4-thiadiazole moiety. Eur. J. Med. Chem., 2014, 86, 676-683.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.032] [PMID: 25222878]
[21]
Sun, N-B.; Fu, J-Q.; Weng, J-Q.; Jin, J-Z.; Tan, C-X.; Liu, X-H. Microwave assisted synthesis, antifungal activity and DFT theoretical study of some novel 1,2,4-triazole derivatives containing the 1,2,3-thiadiazole moiety. Molecules, 2013, 18(10), 12725-12739.
[http://dx.doi.org/10.3390/molecules181012725] [PMID: 24132196]
[22]
Tadikonda, R.; Nakka, M.; Rayavarapu, S.; Kalidindi, S.P.K.; Vidavalur, S. Ligand-free copper (0) catalyzed direct C–H arylation of 1, 2, 4-triazoles and 1, 3, 4-oxadiazoles with aryl iodides in PEG-400. Tetrahedron Lett., 2015, 56(5), 690-692.
[http://dx.doi.org/10.1016/j.tetlet.2014.12.064]
[23]
Al-Soud, Y.A.; Al-Dweri, M.N.; Al-Masoudi, N.A. Synthesis, antitumor and antiviral properties of some 1,2,4-triazole derivatives. Farmaco, 2004, 59(10), 775-783.
[http://dx.doi.org/10.1016/j.farmac.2004.05.006] [PMID: 15474054]
[24]
Sztanke, K.; Tuzimski, T.; Rzymowska, J.; Pasternak, K.; Kandefer-Szerszeń, M. Synthesis, determination of the lipophilicity, anticancer and antimicrobial properties of some fused 1,2,4-triazole derivatives. Eur. J. Med. Chem., 2008, 43(2), 404-419.
[http://dx.doi.org/10.1016/j.ejmech.2007.03.033] [PMID: 17531354]
[25]
Sasikumar, A.; Mohanasrinivasan, V.; Kumar, A.K.A.; Krishnaswamy, D. Design, synthesis, and evaluation of the anticancer properties of a novel series of α-(benzoylamino)-β-substituted acrylic amide derivatives of pyrazolo[1,5-a]pyrimidine. J. Heterocycl. Chem., 2018, 55, 214.
[http://dx.doi.org/10.1002/jhet.3029]
[26]
Amr, A.E.E.; Sabry, N.M.; Abdulla, M.M. Synthesis, and analgesic and antiparkinsonian activities of thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine derivatives from 2-chloro-6-ethoxy-4-acetylpyridine. Monatsh Chem. Chemical, 2008, 138, 699.
[27]
Prakash, O.; Bhardwaj, V.; Kumar, R.; Tyagi, P.; Aneja, K.R. Organoiodine (III) mediated synthesis of 3-aryl/hetryl-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidines as antibacterial agents. Eur. J. Med. Chem., 2004, 39(12), 1073-1077.
[http://dx.doi.org/10.1016/j.ejmech.2004.06.011] [PMID: 15571869]
[28]
Xie, F.; Zhao, H.; Zhao, L.; Lou, L.; Hu, Y. Synthesis and biological evaluation of novel 2,4,5-substituted pyrimidine derivatives for anticancer activity. Bioorg. Med. Chem. Lett., 2009, 19(1), 275-278.
[http://dx.doi.org/10.1016/j.bmcl.2008.09.067] [PMID: 19028425]
[29]
Agarwal, N.; Srivastava, P.; Raghuwanshi, S.K.; Upadhyay, D.N.; Sinha, S.; Shukla, P.K.; Ji Ram, V. Chloropyrimidines as a new class of antimicrobial agents. Bioorg. Med. Chem., 2002, 10(4), 869-874.
[http://dx.doi.org/10.1016/S0968-0896(01)00374-1] [PMID: 11836092]
[30]
Jaman, A.A.; Gopinath, S.K.; Vijay, N.B. Synthesis, antimicrobial activities of pyrano [2,3-d] pyrimidine derivatives. Int. J. Chem. Physic. Sci. IJCPS, 2018, 7
[31]
Shipra, B.; Sumitra, C.; Kapil, B. Biological screening of some novel pyrimidine compounds. Acta Scientific Pharmaceut. Sci., 2018, 2(6)
[32]
Al-Issa, S.A. Synthesis and anticancer activity of some fused pyrimidines and related heterocycles. Saudi Pharm. J., 2013, 21(3), 305-316.
[http://dx.doi.org/10.1016/j.jsps.2012.09.002] [PMID: 23960847]
[33]
Sarmistha, M.; Raju, D. Natural products for the management and prevention of breast cancer; Evidence-Based Complement. Alternat. Med, 2018, p. 8324696.
[34]
Weil, R.J.; Palmieri, D.C.; Bronder, J.L.; Stark, A.M.; Steeg, P.S. Breast cancer metastasis to the central nervous system.. Am. J. Pathol., 2005, 167(4), 913e20.,
[http://dx.doi.org/10.1016/S0002-9440(10)61180-7]
[35]
Berliere, M.; Roelants, F.; Watremez, C.; Docquier, M.A.; Piette, N.; Lamerant, S.; Megevand, V.; Van Maanen Piette, A. P.; Gerday, A.; Duhoux, F.P. The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy. Breast, 2018, 37, 114, e118.,
[http://dx.doi.org/10.1016/j.breast.2017.10.017]
[36]
Li, Z.H.; Yang, D.X.; Geng, P.F.; Zhang, J.; Wei, H.M.; Hu, B.; Guo, Q.; Zhang, X.H.; Guo, W.G.; Zhao, B.; Yu, B.; Ma, L.Y.; Liu, H.M. Design, synthesis and biological evaluation of [1,2,3]triazolo [4,5-d]pyrimidine derivatives possessing a hydrazone moiety as antiproliferative agents. Eur. J. Med. Chem., 2016, 124, 967-980.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.022] [PMID: 27771599]
[37]
Wim, B.; Ibnelwaleed, A.H.; Mohamed, M.; Abdulmujeeb, T.O.; Mohammed, A.S.; Golibjon, R.B. Ind. Eng. Chem. Res., 2018, 57, 10095-10104.https://pubs.acs.org/doi/10.1021/acs.iecr.8b01928
[38]
Derek, T.A.; Jesus, G.E.; Shishi, L.; Spencer, D.D.; Abigail, G.D. Predicting reaction performance in C-N cross-coupling using machine learning. Science, 2018, 360(6385), 186-190.http://science.sciencemag.org/content/early/2018/02/14/science.aar5169
[39]
Abolghasem, B.; Eslam, P.; Mehdi, N.; Saadat, V. QSAR modeling of antimalarial activity of urea derivatives using genetic algorithm-multiple linear regressions. J. Saudi Chem. Soc., 2016, 20(3), 282-290.
[40]
Taourati, A.I.; Ghamali, M.; Chtita, S.; Zaki, H.; Benlyass, M.; Guenoun, F.; Lakhlifi, T.; Bouachrine, M. QSAR studies of the inhibitory activity of a series of substituted indole and derivatives againt Isoprenylcysteine Carboxyl Methyltransferase (ICMT). Int. J. Pharmaceut. Sci. Invent., 2017, 6(1), 6-13.
[41]
Oyebamiji, A.K.; Oyedeji, F.O.; Adejoro, I.A.; Adeleke, B.B. Anti-fungal activities of 2,4-dintrophenyl hydrazones derivatives: DFT and docking approaches. Acad. Arena, 2018, 10(6), 12-16.

Rights & Permissions Print Cite
Article Metrics
23
4
1
© 2024 Bentham Science Publishers | Privacy Policy