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PHARMASPIRE - Volume 11, Issue 3, July - September, 2019

Pages: 88-92

Date of Publication: 14-Jun-2022

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Synthesis, structural identification, and biological evaluation of naphthalene-based pyrimidine

Author: Gurpreet Singh, Vikramdeep Monga

Category: Pharmaceutics


Increasing drug resistance in bacteria and cancer has alarmed the rings to develop newer, safer, and effective treatments against them. In a quest to identify new leads, we synthesized some naphthalene-based pyrimidines and evaluated their antibacterial and cytotoxic potential. The molecules were synthesized through the condensation of naphthalene-based chalcone with guanidine hydrochloride in methanol under reflux conditions. The antibacterial evaluation led to the identification of compound 5b as the most potent molecule of the series. Compound 5c was found to be the most potent against colo-205, while 5a displayed the highest activity against A-549.

Keywords: Pyrimidines, naphthalene, antibacterial, cytotoxicity, chalcones


1. Hassanpour SH, Dehghani M. Review of cancer from the perspective of molecular. J Cancer Res Pract 2017;17:127-9.

2. Siegel R, Naishadham D. Cancer statistics. Cancer J Clin 2013;63:11-30.

3. Nurgali K, Jagoe RT, Abalo R. Adverse effects of cancer chemotherapy. Front Pharmacol 2018;9:245-7.

4. Zhao G, Rodriguez BL. Molecular targeting of liposomal nanoparticles to tumor microenvironment. Int J Nanomed 2013;8:61-71.

5. Renwick MJ, Brogan DM, Mossialos E. A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics. J Antibiot (Tokyo) 2016;69:73-88.

6. Kinch MS, Patridge E, Plummer M, Hoyer D. An analysis of FDA-approved drugs for infectious disease: Antibacterial agents. Drug Discov Today 2014;19:1283-7.

7. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: Confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 2007;6:29-40.

8. Blaser M. Stop the killing of beneficial Bacteria. Nature 2011;476:393-4.

9. Brown ED, Wright GD. Antibacterial drug discovery in the resistance era. Nature 2016;529:336-43.

10. Brown DJ. Pyrimidines; their benzo derivatives. In: Katritzky AR, Rees CW, editors. Comprehensive Heterocyclic Chemistry. Vol. 3. Oxford: Pergamon Press; 1984. p. 443.

11. Roth B, Cheng C. In: Ellis GP, West GB, editors. Progress in Medicinal Chemistry. Vol. 19. New York: Elsevier Biomedical Press; 1982. p. 267.

12. El-Gaby EA, Abdel-Hamide SG, Ghorab MM, El-Sayed SM. Synthesis and anticancer activity in vitro of some new pyrimidines. Acta Pharm 1999;49:149-58.

13. Nasr MN, Gineinah MM. Pyrido2,3-dpyrimidines and pyrimido5’,4’:5,6pyrido2,3-dpyrimidines as new antiviral agents: Synthesis and biological activity. Arch Pharm 2002;335:289-95.

14. Baraldi PG, Pavani MG, Nunez M, Brigidi P, Vitali B, Gambari R, et al. Antimicrobial and antitumor activity of N-heteroimine-1,2,3-dithiazoles and their transformation in triazolo-, imidazo-and pyrazolopyrimidines. Bioorg Med Chem 2002;10:449-56.

15. Sondhi SM, Johar M, Rajvanshi S, Dastidar SG, Shukla R, Raghubir R, et al. Anticancer, anti-inflammatory and analgesic activity evaluation of heterocyclic compounds synthesized by the reaction of 4-isothiocyanato-4-methylpentan2-one with substituted o-phenylenediamines, o-diaminopyridine and (un) substituted o-diaminopyrimidines. Aust J Chem 2001;54:69-74.

16. Mangalagiu G, Ungureanu M, Grosu G, Mangalagiu I, Petrovanu M. New pyrrolo-pyrimidine derivatives with antifungal or antibacterial properties. Ann Pharm Fr 2001;59:139-40.

17. Batovska DI, Todorova IT. Trends in utilization of the pharmacological potential of chalcones. Curr Clin Pharmacol 2010;5:1-29.

18. de Mello TF, Bitencourt HR, Pedroso RB, Aristides SM, Lonardoni MV, Silveira TG. Leishmanicidal activity of synthetic chalcones in Leishmania (viannia) Braziliensis. Exp Parasitol 2014;136:27-34.

19. Mishra N, Arora P, Kumar B, Mishra LC, Bhattacharya A, Awasthi SK, et al. Synthesis of novel substituted 1,3-diaryl propenone derivatives and their antimalarial activity in vitro. Eur J Med Chem 2008;43:1530-5.

20. Sinha S, Medhi B, Sehgal R. Chalcones as an emerging lead molecule for antimalarial therapy: A review. J Mod Med Chem 2013;1:64-77.

21. Powers DG, Casebier DS, Fokas D, Ryan WJ, Troth JR, Cofen DL. Automated parallel synthesis of chalcone-based screening libraries. Tetrahedron 1998;54:4085-96.

22. Kumar R, Mohanakrishnan D, Sharma A, Kaushik NK, Kalia K, Sinha AK, et al. Reinvestigation of structure-activity relationship of methoxylated chalcones as antimalarials: Synthesis and evaluation of 2,4,5-trimethoxysubstituted patterns as lead candidates derived from abundantly available natural β-asarone. Eur J Med Chem 2010;45:5292-303.

23. Go ML, Liu M, Wilairat P, Rosenthal PJ, Saliba KJ, Kirk K. Antiplasmodial chalcones inhibit sorbitol-induced hemolysis of Plasmodium falciparum infected erythrocytes. Antimicrob Agents Chemother 2004;48:3241-5.

24. Chen M, Theander TG, Christensen SB, Hviid L, Zhai L, Kharazmi A. Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection. Antimicrob Agents Chemother 1994;38:1470-5.

25. Liu M, Wilairat P, Go ML. Antimalarial alkoxylated and hydroxylated chalones: Structure-activity relationship analysis. J Med Chem 2001;44:4443-52.