Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Research Article

Design, Synthesis and Biological Potential of 5-(2-Amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol Scaffolds as Promising Antimicrobial and Anticancer Agents

Author(s): Sanjiv Kumar, Balasubramanian Narasimhan*, Siong Meng Lim, Kalavathy Ramasamy, Vasudevan Mani and Syed Adnan Ali Shah

Volume 19, Issue 10, 2019

Page: [851 - 864] Pages: 14

DOI: 10.2174/1389557518666181009141924

Price: $65

Abstract

Background: A series of 5-(2-amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol scaffolds was synthesized by Claisen-Schmidt condensation and characterized by NMR, IR, Mass and elemental analyses.

Methods: The synthesized pyrimidine scaffolds were screened for their antimicrobial activity by tube dilution method as well for antiproliferative activity (human colorectal (HCT116) cancer cell line) by SRB assay.

Results: The antimicrobial screening results demonstrated that compounds, k6, k12, k14 and k20 were found to be the most potent ones against selected microbial species. The anticancer screening results indicated that compounds, k8 and k14 displayed potent anticancer activity against cancer cell line (HCT116).

Conclusion: Further, the molecular docking study carried to find out the interaction between active pyrimidine compounds with CDK-8 protein indicated that compound k14 showed best dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

Keywords: Antibacterial activity, antifungal activity, docking, cytotoxicity, mechanism, pyrimidine scaffolds, synthesis.

« Previous
Graphical Abstract
[1]
Kotaiah, Y.; Nagaraju, K.; Harikrishna, N.; Rao, C.V.; Yamini, L.; Vijjulatha, M. Synthesis, docking and evaluation of antioxidant and antimicrobial activities of novel 1,2,4-triazolo [3,4-b][1,3,4]-thiadiazol-6-yl) selenopheno [2,3-d]pyrimidines. Eur. J. Med. Chem., 2014, 75, 195-202.
[2]
Mallikarjunaswamy, C.; Mallesha, L.; Bhadregowda, D.G.; Pinto, O. Studies on synthesis of pyrimidine derivatives and their antimicrobial activity. Arab. J. Chem., 2014, 7, 986-993.
[3]
Wang, H.C.; Yan, X.Q.; Yan, T.L.; Li, H.X.; Wang, Z.C.; Zhu, H.L. Design, synthesis and biological evaluation of benzohydrazide derivatives containing dihydropyrazoles as potential EGFR kinase inhibitors. Molecules, 2016, 21(8)pii: E1012
[4]
Liu, Z.; Wang, Y.; Lin, H.; Zuo, D.; Wang, L.; Zhao, Y.; Gong, P. Design, synthesis and biological evaluation of novel thieno [3,2-d]pyrimidine derivatives containing diaryl urea moiety as potent antitumor agents. Eur. J. Med. Chem., 2014, 85, 215-227.
[5]
Kumar, S.; Lim, S.M.; Ramasamy, K.; Vasudevan, M.; Shah, S.A.A.; Selvaraj, M.; Narasimhan, B. Synthesis, molecular docking and biological evaluation of bis-pyrimidine Schiff base derivatives. Chem. Cent. J., 2017, 11(89), 1-16.
[6]
Peyressatre, M.; Prével, C.; Pellerano, M.; Morris, M.C. Targeting cyclin-dependent kinases in human cancers: from small molecules to peptide inhibitors. Cancer, 2015, 7, 179-237.
[7]
Anupama, B.; Dinda, S.C.; Prasad, Y.R.; Rao, A.V. Synthesis and antimicrobial activity of some new 2,4,6-trisubstituted pyrimidines. Int. J. Res. Pharm. Chem., 2012, 2(2), 231-236.
[8]
Chen, Q.; Zhu, X.L.; Jiang, L.L.; Liu, Z.M.; Yang, G.F. Synthesis, antifungal activity and CoMFA analysis of novel 1,2,4-triazolo [1,5-a]pyrimidine derivatives. Eur. J. Med. Chem., 2008, 43, 595-603.
[9]
El-Gaby, M.S.A.; Gaber, A.M.; Atalla, A.A.; Al-Wahab, K.A.A. Novel synthesis and antifungal activity of pyrrole and pyrrolo [2,3-d]pyrimidine derivatives containing sulfonamide moieties. Il Farmaco, 2002, 57, 613-617.
[10]
Xu, X.; Wang, J.; Yao, Q. Synthesis and quantitative structure-activity relationship (QSAR) analysis of some novel oxadiazolo [3,4-d]pyrimidine nucleosides derivatives as antiviral agents. Bioorg. Med. Chem. Lett., 2015, 25, 241-244.
[11]
Tian, Y.; Du, D.; Rai, D.; Wang, L.; Liu, H.; Zhan, P.; Clercq, E.D.; Pannecouque, C.; Liu, X. Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: Design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo [1,5-a]pyrimidine derivatives. Bioorg. Med. Chem., 2014, 22, 2052-2059.
[12]
Tozkoparan, B.; Ertan, M.; Kelicen, P.; Demirdamar, R. Synthesis and anti-inflammatory activities of some thiazolo [3,2-a]pyrimidine derivatives. Il Farmaco, 1999, 54, 588-593.
[13]
Agarwal, A. Srivastava. K.; Puri, S.K.; Chauhan, P.M. Synthesis of 2,4,6-trisubstituted pyrimidines as antimalarial agents. Bioorg. Med. Chem., 2005, 13, 4645-4650.
[14]
Kumar, D.; Khan, S.I.; Tekwani, B.L.; Ponnan, P.; Rawat, D.S. 4-Aminoquinoline-pyrimidine hybrids: synthesis, antimalarial activity, heme binding and docking studies. Eur. J. Med. Chem., 2015, 89, 490-502.
[15]
Flefel, E.M.; El-Sayed, W.A.; Mohamed, A.M.; El-Sofany, W.I.; Awad, H.M. Synthesis and anticancer activity of new 1-thia-4-azaspiro[4.5]decane, their derived thiazolopyrimidine and 1,3,4-thiadiazole thioglycosides. Molecules, 2017, 22, 1-13.
[16]
Amer, S.; El-Wakiel, N.; El-Ghamry, H. Synthesis, spectral, antitumor and antimicrobial studies on Cu (II) complexes of purine and triazole Schiff base derivatives. J. Mol. Struct., 2013, 1049, 326-335.
[17]
Bhalgat, C.M.; Ali, M.I.; Ramesh, B.; Ramu, G. Novel pyrimidine and its triazole fused derivatives: synthesis and investigation of antioxidant and anti-inflammatory activity. Arab. J. Chem., 2014, 7, 986-993.
[18]
Suryawanshi, S.N.; Kumar, S.; Shivahare, R.; Pandey, S.; Gupta, S.; Tiwari, A. Design, synthesis and biological evaluation of aryl pyrimidine derivatives as potential leishmanicidal agents. Bioorg. Med. Chem. Lett., 2013, 23, 5235-5238.
[19]
Amin, K.M.; Awadalla, F.M.; Eissa, A.A.M. Abou- Seri, A.M.; Hassan, G.S. Design, synthesis and vasorelaxant evaluation of novel coumarin-pyrimidine hybrids. Bioorg. Med. Chem., 2011, 19, 6087-6097.
[20]
Chen, P.J.; Yang, A.; Gu, Y.F.; Zhang, X.S.; Shao, K.P.; Xue, D.Q.; He, P.; Jiang, T.F.; Zhang, Q.R. Liu. H.M. Synthesis, in vitro antimicrobial and cytotoxic activities of novel pyrimidine-benzimidazol combinations. Bioorg. Med. Chem. Lett., 2014, 24, 2741-2743.
[21]
Mohana, K.N.; Kumar, B.N.P.; Mallesha, L. Synthesis and biological activity of some pyrimidine derivatives. Drug Invent Today, 2013, 5, 216-222.
[22]
Yejella, R.P.; Atla, S.R. A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted pyrimidines. Chem. Pharm. Bull., 2011, 59(9), 1079-1082.
[23]
Fares, M.; Abou-Seri, S.M.; Abdel-Aziz, H.A.; Abbas, S.E.S.; Youssef, M.M.; Eladwy, R.A. Synthesis and antitumor activity of pyrido [2,3-d]pyrimidine and pyrido [2,3-d][1,2,4]triazolo [4,3-a] pyrimidine derivatives that induce apoptosis through G1 cell-cycle arrest. Eur. J. Med. Chem., 2014, 83, 155-166.
[24]
El-Sayed, N.S.; El-Bendary, E.R.; Saadia, M.; El-Ashry, S.M.; El-Kerdawy, M.M. Synthesis and antitumor activity of new sulfonamide derivatives of thiadiazole [3,2-a]pyrimidines. Eur. J. Med. Chem., 2011, 46, 3714-3720.
[25]
Asiri, A.M.; Khan, S.A. Synthesis and anti-bacterial activities of a bis-chalcone, derived from thiophene and its bis-cyclized products. Molecules, 2011, 16, 523-531.
[26]
Parveen, H.; Hayat, F.; Mukhtar, S.; Salahuddin, A.; Khan, A.; Islam, F.; Azam, A. Synthesis, characterization and biological evaluation of novel 2,4,6-trisubstituted bis-pyrimidine derivatives. Eur. J. Med. Chem., 2011, 46, 4669-4675.
[27]
Cappuccino, J.C.; Sherman, N. Microbiology-a laboratory manual. Addison Wesley, California, p. 263. 1999.
[28]
Indian Pharmacopoeia Commission, Pharmacopoeia of India, vol. I. Controller of publication, ministry of health department, Govt of India, New Delhi, p. 37. 2007.
[29]
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[30]
Kaur, R.; Kaur, P.; Sharma, S.; Singh, G.; Mehndiratta, S.; Bedi, P.M.; Nepali, K. Anti-cancer pyrimidines in diverse scaffolds: a review of patent literature. Rec. Pat. Anti-Canc., 2015, 10(1), 23-71.
[31]
Singh, J.; Kumar, M.; Mansuri, R.; Sahoo, G.C.; Deep, A. Inhibitor designing, virtual screening and docking studies for methyltransferase: a potential target against dengue virus. J. Pharm. Bioallied Sci., 2016, 8(3), 188-194.
[32]
Maddila, S.; Gorle, S.; Seshadri, N.; Lavanya, P.; Jonnalagadda, S.B. Synthesis, antibacterial and antifungal activity of novel benzothiazole pyrimidine derivatives. Arab. J. Chem., 2016, 9, 681-687.
[33]
Sharma, V.; Chitranshi, N.; Agarwal, A.K. Significance and biological importance of pyrimidine in the microbial world. Int. J. Med. Chem., 2014, 2014202784

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy