Research Article | Volume: 9, Supplement 1, March, 2019

Synthesis and antibacterial evaluation of new azo-pyrimidine derivatives

Mohamed A. Abdelgawad   

Open Access   

Published:  Mar 08, 2019

DOI: 10.7324/JAPS.2019.S102
Abstract

The synthesis of potent antibacterial agents, free from side effects and resistant to bacterial enzymes, is the main objective for drug designers. Also, the multi-target drugs have an important role in advanced drug synthesis. The azo-malonate compounds II a & b were prepared from the diazo coupling reaction of aniline derivatives with the acidic methylene group of diethyl malonate. The new azo-malonate derivatives II a–c were reacted with urea or thiourea in the presence of sodium ethoxide, afforded the target new azo-pyrimidine compounds III a & b and IV a & b. The structure of the new compounds was elucidated by using NMR, IR, mass spectroscopy, and elemental analysis. The minimum inhibitory concentration of new azo-compounds III a & b and IV a & b was evaluated for their antibacterial activity. Two new synthesized azo-compounds showed weak (III b) to strong (IV b) antibacterial activity. The molecular operating environment docking program was used for the prediction of the compound IV b action mechanism.


Keyword:     Antibacterial pyrimidine diethyl malonate pyrimidinone.


Citation:

Abdelgawad MA. Synthesis and antibacterial evaluation of new azo-pyrimidine derivatives. J Appl Pharm Sci, 2019; 9(S1):009–016.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

Abd-El Gawad NM, Georgey HH, Ibrahim NA, Amin NH, Abdelsalam RM. Synthesis of novel pyrazole and dihydropyrazoles derivatives as potential anti-inflammatory and analgesic agents. Arch Pharm Res, 2012; 35(5):807–21. https://doi.org/10.1007/s12272-012-0507-y

Abdelgawad MA, Bakr RB, Omar HA. Design, synthesis and biological evaluation of some novel benzothiazole/benzoxazole and/or benzimidazole derivatives incorporating a pyrazole scaffold as antiproliferative agents. Bioorg Chem, 2017; 74:82–90. https://doi.org/10.1016/j.bioorg.2017.07.007

Abdelgawad MA, Labib MB, Ali WAM, Kamel G, Azouz AA, EL-Nahass ES. Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: histopathological and docking studies. Bioorg Chem, 2018; 78:103–14. https://doi.org/10.1016/j.bioorg.2018.03.011

Awadallah FM, Piazza GA, Gary BD, Keeton AB, Canzoneri JC. Synthesis of some dihydropyrimidine-based compounds bearing pyrazoline moiety and evaluation of their antiproliferative activity. Eur J Med Chem, 2013; 70:273–9. https://doi.org/10.1016/j.ejmech.2013.10.003

Bakulev VA, Berseneva VS, Belskaia NP, Morzherin YY, Zaitsev A, Dehaen W, Luytenb I, Toppet S. Reactions of 5-mercaptoazoles and pyridine-2-thiones with acetylenic esters. Selectivity of the formation of novel fused thiazin-4-ones and thiazolidin-4-ones. Org Biomol Chem, 2003; 1:134–9. https://doi.org/10.1039/b207854f

Bansal S, Bala M, Suthar SK, Choudhary S, Bhattacharya S, Bhardwaj V, Singla S, Joseph A. Design and synthesis of novel 2-phenyl-5-(1,3- diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity. Eur J Med Chem, 2014; 80:167–74. https://doi.org/10.1016/j.ejmech.2014.04.045

Belal A, Abdelgawad MA. New benzothiazole/benzoxazole-pyrazole hybrids with potential as COX inhibitors: design, synthesis and anticancer activity evaluation. Res Chem Intermediat, 2017; 43 (7):3859–72. https://doi.org/10.1007/s11164-016-2851-x

Cheng CC, Roth B. Recent progress in the medicinal chemistry of 2,4-diaminopyrimidines. Prog Med Chem 1982; 19:269–331. https://doi.org/10.1016/S0079-6468(08)70332-1

Etman HA, Sadek MG, Khalil AGM. Synthesis of some new heterocycles derived from 3-amino-5hydrazinopyrazole dihydrochloride. Res J Pharm Biol Chem Sci, 2015; 6(2):247–54.

Gadhaveb A, Gaikar R, Kuchekar S, Karale B. Synthesis and antimicrobial evaluations of some novel fluorinated chromones and pyrazoles. Indian J Chem, 2015; 54(3):383–90.

Kalluraya B, Isloor AM, Frank PV, Jagadeesha RL. Synthesis and pharmacological activity of 4-(substituted)-2-[4-aryl-hydrazono-3- methyl-5-oxo-2-pyrazolin-1-yl]-thiazoles. Indian J Heterocycl Chem, 2004; 13(3):245–8.

Koca M, Servi S, Kirilmis C, Ahmedazade M, Kazaz C, Özbek B, Ötük G. Synthesis and antimicrobial activity of (benzofuran-2-yl) (3-phenyl-3-methylcyclobutyl) ketoxime derivatives. Eur J Med Chem, 2005; 40:1351–8. https://doi.org/10.1016/j.ejmech.2005.07.004

Mallikarjunaswamya C, Malleshab L, Bhadregowda DG, Pintoa O. Studies on synthesis of pyrimidine derivatives and their antimicrobial activity. Arab J Chem, 2017; 10(Supplement 1):S484–90. https://doi.org/10.1016/j.arabjc.2012.10.008

Mandha SR, Siliveri S, Alla M, Bommena VR, Bommineni MR, Balasubramanian S. Eco-friendly synthesis and biological evaluation of substituted pyrano[2,3-c]pyrazoles. Bioorg Med Chem Lett, 2012; 22:5272–8. https://doi.org/10.1016/j.bmcl.2012.06.055

Rahmi K, Metin B, Seckin B, Arslan BG. Synthesis, characterization and antiglaucoma activity of some novel pyrazole derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide. Eur J Med Chem, 2010; 45:4769–73. https://doi.org/10.1016/j.ejmech.2010.07.041

Sader HS, Flamm RK, Jones RN. Antimicrobial activity of daptomycin tested against Gram-positive pathogens collected in Europe, Latin America, and selected countries in the Asia-Pacific Region. Diagn Microbiol Infect Dis, 2013; 75:417–22. https://doi.org/10.1016/j.diagmicrobio.2013.01.001

Saundane AR, Verma VA, Vijaykumar K. Synthesis of some new indolo[2,3-c] isoquinolinyl pyrazoles, -1,3,4-oxadiazoles and their biological activities. Med Chem Res, 2013; 22:3787–93. https://doi.org/10.1007/s00044-012-0366-6

Sayed HH, Hashem AI, Yousif NM, El-Sayed WA. Conversion of 3-Arylazo-5-phenyl-2(3H)-furanones into other heterocycles of anticipated biological activity. Arch Pharm Chem Life Sci, 2007; 340:315–9. https://doi.org/10.1002/ardp.200700043

Schneider P, Hawser S, Islam K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett, 2003; 13(23):4217–21. https://doi.org/10.1016/j.bmcl.2003.07.023

Riyadh SM, Farghaly TA, Abdallah MA, Abdalla MM, Abd El-Aziz MR. New pyrazoles incorporating pyrazolylpyrazole moiety: Synthesis, anti-HCV and antitumor activity. Eur J Med Chem, 2010; 45:1042–50. https://doi.org/10.1016/j.ejmech.2009.11.050

Tarek, N, Hassan HM, AbdelGhani SM, Radwan IA, Hammouda O, El-Gendy AO. Comparative chemical and antimicrobial study of nine essential oils obtained from medicinal plants growing in Egypt. Beni-Suef Univ J Basic Appl Sci, 2014; 3:149–56. https://doi.org/10.1016/j.bjbas.2014.05.009

Vinita S, Nitin C, Ajay KA. Significance and biological importance of pyrimidine in the microbial world. Int J Med Chem, 2014; ID 202784:1–32.

Zaini E, Sumirtapura YC, Halim A, Fitriani L, Soewandhi SN. Formation and characterization of sulfamethoxazole-trimethoprim cocrystal by milling process. J Appl Pharm Sci, 2017; 7(12):169–73.

Article Metrics
613 Views 102 Downloads 715 Total

Year

Month

Related Search

By author names