Abstract
This report describes the novel approach for the synthesis and exploration of hybrid molecules containing pyrimidine-based imidazole scaffolds as potent antimicrobial agents. The targeted compounds N-(4-arylidene-2-mercapto-5-oxo-4,5-dihydro-1H-imidazol-1-yl)-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamides (5a–l) were achieved by the Knoevenagel condensation of a key precursor (4) with different aldehydes in good yields having moderate to excellent antimicrobial activity. The structural identification of final products was carried out by known classical spectral techniques like IR, 1H NMR, 13C NMR, and mass spectra. The obtained data indicated that the majority of the tested compounds exhibited good antibacterial activity over antifungal activity, particularly compounds 5j and 5b (having MIC values 12.5 μg/mL) showed a comparable effect to a standard antibacterial and antifungal agents.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alam O, Khan SA, Siddiqui N, Ahsan W, Verma SP, Gilani SJ (2010) Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides: synthesis and pharmacological evaluation. Euro J Med Chem 45(11):5113–5119
Atwal KS, Swanson BN, Unger SE, Floyd DM, Moreland S, Hedberg A, O’Reilly B (1991) Dihydropyrimidine calcium channel blockers. 3. 3-carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents. J Med Chem 34:806–811
Babizhayev MA (2006) Biological activities of the natural imidazole-containing peptidomimetics n-acetylcarnosine, carcinine and l-carnosine in ophthalmic and skin care products. Life Sci 78:2343–2357
Barrow JC, Nantermet PG, Selnick HG, Glass KL, Rittle KE, Gilbert KF, Steele TG, Homnick CF, Freidinger RM (2000) In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha (1A) receptor antagonists for the treatment of benign prostatic hyperplasia. J Med Chem 43:2703–2718
Baviskar AT, Madaan C, Preet R, Mohapatra P, Jain V, Agarwal A, Guchhait SK, Kundu CN, Banerjee UC, Bharatam PV (2011) N-fused imidazoles as novel anticancer agents that inhibit catalytic activity of topoisomerase IIα and induce apoptosis in G1/S phase. J Med Chem 54(14):5013–5030
Cho H, Ueda M, Shima K, Mizuno A, Hayashimatsu M, Ohnaka Y, Takeuchi Y, Hamaguchi M, Aisaka K, Hidaka T, Kawai M, Takeda M, Ishihara T, Funahashi T, Satoh F, Morita M, Noguchi T (1989) Dihydropyrimidines: novel calcium antagonists with potent and long-lasting vasodilative and antihypertensive activity. J Med Chem 32:2399–2406
Congiu C, Cocco MT, Onnis V (2008) Design, synthesis, and in vitro antitumor activity of new 1,4-diarylimidazole-2-ones and their 2-thione analogues. Bioorg Med Chem Lett 18:989–993
Desai NC, Joshi VV, Rajpara KM, Vaghani HV, Satodiya HM (2013a) Microwave-assisted synthesis and antimicrobial screening of new imidazole derivatives bearing 4-thiazolidinone nucleus. Med Chem Res 22:1893–1908
Desai NC, Rajpara KM, Joshi VV (2013b) Synthesis of pyrazole encompassing 2-pyridone derivatives as antibacterial agents. Bioorg Med Chem Lett 23:2714–2717
Desai NC, Vaghani HV, Shihora PN (2013c) A new hybrid approach and in vitro antimicrobial evaluation of novel 4(3H)-quinazolinones and thiazolidinone motifs. J Fluor Chem 153:39–47
Diaa AI, Amira ME (2010) Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. Euro J Med Chem 45(3):1158–1166
Ding HX, Liu KKC, Sakya SM (2013) Synthetic approaches to the new drugs. Bioorg Med Chem 21:2795–2825
Grover GJ, Dzwonczyk S, McMullen DM, Normandin DE, Parham CS, Sleph PG, Moreland S (1995) Pharmacologic profile of the dihydropyrimidine calcium channel blockers SQ 32,547 and SQ 32,946. J Cardiovasc Pharmacol 26:289–294
Gupta RR, Kumar M, Gupta V (2005) Five-membered heterocycles with more than two heteroatoms. Heterocyclic chemistry, vol 2, II edn. Springer (India) Pri. Lim, New Delhi, p 540
Kumar A, Sharma P, Kumari P, Kalal BL (2011) Exploration of antimicrobial and antioxidant potential of newly synthesized 2,3-disubstituted quinazoline-4(3H)-ones. Bioorg Med Chem Lett 21(14):4353–4357
Nakamura T, Kakinuma H, Umemiya H, Amada H, Miyata N, Taniguchi K, Bando K, Sato M (2004) Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors. Bioorg Med Chem Lett 14:333–336
Nantermet PG, Barrow JC, Lindsley SR, Young M, Mao S, Carroll S, Bailey C, Bosserman M, Colussi D, McMasters DR, Vacca JP, Selnick HG (2004) Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P(1)(′) group. Bioorg Med Chem Lett 14:2141–2145
Ohishi Y, Mukai T, Nagahara M, Yajima M, Kajikawa N, Miyahara K, Takano T (1990) Preparations of 5-alkylmethylidene-3carboxymethylrhodanine derivatives and their aldose reductase inhibitory activity. Chem Pharm Bull 38:1911–1919
Pozharskii AF et al (1997) Heterocycles in life and society. Wiley, New York
Raval JP, Akhaja TN (2011) 1,3-dihydro-2H-indol-2-ones derivatives: design, synthesis, in vitro antibacterial, antifungal and antitubercular study. Eur J Med Chem 46:5573–5579
Rostamizadeh S, Nojavan M, Aryan R, Sadeghian H, Davoodnejad M (2013) A novel and efficient synthesis of pyrazolo[3,4-d]pyrimidine derivatives and the study of their anti-bacterial activity. Chin Chem Lett 24(7):629–632
Rovnyak GC, Atwal KS, Hedberg A, Kimball SD, Moreland S, Gougoutas JZ, O’Reilly BC, Schwartz J, Malley MF (1992) Dihydropyrimidine calcium channel blockers. 4. Basic 3-substituted-4-aryl-1,4-dihydropyrimidine-5-carboxylic acid esters. Potent antihypertensive agents. J Med Chem 35:3254–3263
Samshuddin S, Narayana B, Sarojini BK, Shetty DN, Kumari NS (2012) Synthesis, characterization and biological evaluation of some new functionalized terphenyl derivatives. Int J Med Chem 2012:13. doi:10.1155/2012/530392
Singh K, Arora D, Singh K, Singh S (2009) Genesis of dihydropyrimidinone calcium channel blockers: recent progress in structure–activity relationships and other effects. Mini Rev Med Chem 9:95–106
Sondhia SM, Dinodia M, Rani R, Shukla R, Raghubir R (2009) Synthesis, anti-inflammatory and analgesic activity evaluation of some pyrimidine derivatives. Indian J Chem 49B:273–281
Venkatesan AM, Agarwal A, Abe T, Ushirogochi HO, Santos D, Li Z, Francisco G, Lin YI, Peterson PJ, Yang Y, Weiss WJ, Shales DM, Mansour TS (2008) 5,5,6-Fused tricycles bearing imidazole and pyrazole 6-methylidene penems as broad-spectrum inhibitors of beta-lactamases. Bioorg Med Chem 16:1890–1902
Virsodia V, Pissurlenkar RRS, Manvar D, Dholakia C, Adlakha P, Shah A, Coutinho EC (2008) Synthesis, screening for antitubercular activity and 3D-QSAR studies of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxamides. Eur J Med Chem 43:2103–2115
Vladimir VK, Alicia GB (2009) Recent developments in the design and synthesis of hybrid molecules based on aminoquinoline ring and their antiplasmodial evaluation. Eur J Med Chem 44:3091–3113
Wallis MP, Mahmood N, Fraser WW (1999) Synthesis and anti-HIV activity of C4-modified pyrimidine nucleosides. Il Farmaco 54:83–89
Acknowledgments
We express our sincere gratitude to the Department of Chemistry (UGC Non-SAP & DST-FIST Sponsored), Mahatma Gandhi Campus, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar for providing research and library facilities.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Desai, N.C., Vaghani, H.V., Rajpara, K.M. et al. Novel approach for synthesis of potent antimicrobial hybrid molecules containing pyrimidine-based imidazole scaffolds. Med Chem Res 23, 4395–4403 (2014). https://doi.org/10.1007/s00044-014-1005-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-014-1005-1