Facile Synthesis, Characterization of New Quinazolinones with Different Azo Compounds, 1,2,3-Triazole Moieties and Evaluation Their Anti-bacterial Activity.

Ayad Kareem Khan

doi:10.23851/mjs.v28i3.180

Authors

Ayad Kareem Khan Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Mustansiriyah University, Baghdad, Iraq http://orcid.org/0000-0002-2353-6444

DOI:

https://doi.org/10.23851/mjs.v28i3.180

Keywords:

Synthesis, Characterization, Quinazolinone, Azo Compounds 1, 2, 3-Triazole, Anti-bacterial.

Abstract

In the present research, a series of some azo compounds (5-9) and 1,2,3-triazoles derived from 2-methyl quinazolin-4(3H)-one were synthesized successfully by stepwise routes includes the following: 3-amino-2-methylquinazolin-4(3H)-one (3) prepared firstly by conversion of 2-aminobenzoic acid into methyl 2-aminobenzoate (1) followed by reaction with acetic anhydride to form methyl -2-acetamidobenzoate (2). The amide then allowed reacting with hydrazine hydrate to give compound (3). Diazotization reaction with sodium nitrite in the presence of hydrochloric acid yield the 3-(chlorodiazenyl)-2-methylquinazolin-4(3H)-one(4). Diazonium salt (4) then enter two different routes. The first route was its conversion into azo compounds (5-9) by reaction with coupling components.The second route included formation of 1,2,3- triazole derivatives by interconversion of compound (4) into azido compound (10) followed by treatment with ethyl acetoacetate, acetyl acetone to give 5-methyl-1-(2-methyl-4-oxoquinazolin-3(4H)-yl)-1H-1,2,3-triazole-4-carboxylic acid (11) and 3-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-methylquinazolin-4(3H)-one (12) in good yield. Newly synthesized derivatives were characterized spectroscopically by FTIR, 13C-NMR and 1H-NMR spectral technique and by determination of their physical properties. Also end time of reactions monitored by thin layer chromatography. The antibacterial potential of synthesized azo compounds, 1,2,3-triazole of methyl quinazolin-4(3H)-one has been tested against the growth of four gram positive and gram negative pathogenic bacterial strains using agar well diffusion method. Ampicillin trihydrate used as reference drug. The results of the antibacterial study showed that compounds (7-9) appeared good activity.

Downloads

Download data is not yet available.

References

Imtiaz K , Sumera Z, Sadaf B, Naeem A, Zaman A, Jamshed I, Aamer S. Quinazolines and quinazolinones as ubiquitous structural fragments in medicinal chemistry: An update on the development of synthetic methods and pharmacological diversification. Bioorg. Med. Chem., 24(11): 2361-2381 (2016).

Ajit K, Yongzheng Z, Kurt W, Padmanava P, Malvika K, Kalkal T, Daniel S, Edmond J. Antibacterial activity of quinoxalines, quinazolines, and 1,5-naphthyridines. Bioorg. Med. Chem. Lett., 23(17): 4968–4974 (2013).

Shalaby A, El-Khamry A, Shiba S, Ahmed A, Hanafi A. Synthesis and antifungal activity of some new quinazoline and benzoxazinone derivatives. Arch Pharm., 333(11):365-372 (2000).

Joshua O, Theresa O, Edward A, Torey A, Mai A, Julie E. Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents. Bioorg. Med. Chem., 22 (24): 6965-6979 (2014).

Felix E, Anton A, Tony F, Frank H, Axel K. Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions. Nat. Commun., 8, 1-9 (2017).

Ochiai T, Ishida R. Pharmacological studies on 6-amino- 2-fluoromethyl- 3-(O-tolyl)- 4(3H)- quinazolinone (afloqualone), a new centrally acting muscle relaxant. (II) Effects on the spinal reflex potential and the rigidity. Jap. J. Pharm., 32(3):427-38. (1982).

Rojas-Aguirre Y, Hernandez-Luis F, Mendoza-Martínez C, Sotomayor C, Aguilar L, Villena F, Castillo I, Hernandez D, Suwalsky M. Effects of an antimalarial quinazoline derivative on human erythrocytes and on cell membrane molecular models. Biochim. Biophys. Acta., 1818(3):738-746 (2012).

Maarouf A, El-Bendary E, Goda F. Synthesis and evaluation of some novel quinazolinone derivatives as diuretic agents. Arch Pharm., 337(10):527-532 (2004).

Mendoza C, Correa J, Nieto R, Marquez A, Aguilar R. Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents. Eur. J. Med. Chem., 96:296-307 (2015).

Jatav V, Mishra P, Kashaw S, Stables JP. Synthesis and CNS depressant activity of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones. Eur. J. Med. Chem., 43(1):135-141 (2008).

Hughes A, Rafi I, Griffin M, Phase I studies with the nonclassical antifolate nolatrexed dihydrochloride (AG337, THYMITAQ) administered orally for 5 days. Clin. Cancer Res., 5 (1): 111-118 (1999).

Remi G, Fabrice P, Carine P, Damien H, Alain T. Discovery of a novel broad-spectrum antifungal agent derived from albaconazole. ACS Med. Chem. Lett., 4 (2): 288-292 (2013).

Ishikawa T, Kamide R, Niimura M. Photo leukome lanodermatitis (Kobori) induced by afloqualone. J. Dermato., 21(6):430-433 (1994).

Clissold S, Beresford R. Proquazone. A review of its pharmacodynamics and pharmacokinetic properties, and therapeutic efficacy in rheumatic diseases and pain states. Drugs, 33 (5): 478-502 (1987).

Yang Y, Rasmussen B, Shlaes D. Class A beta-lactamases enzyme inhibitor interactions and resistance. Pharmacol. Ther., 83, 141-151 (1999).

Krasimira T, Taterao M, Paula C. Antimicrobial and cytotoxic activities of 1,2,3-triazole-sucrose derivatives. Carbohydrate Res.,417(19): 66-71 (2015).

Lazrek H, Taourirte M, Oulih T, Barascut J, Imbach J, Pannecouque C. Synthesis and anti-HIV activity of new modified 1,2,3-triazole acyclonucleosides. Nucleosides Nucleotides Nucleic Acids., 20(12):1949-1960 (2001).

Derek R, Caroline J.M, Harry S, Barbara A. Studies on 1,2,3,-triazoles. Synthesis and antiallergic properties of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazoles and their S-oxides. J. Med. Chem., 27 (2): 223-227(1984).

Esra D, Dilek U, Fatih C, Kemal S, Sengul A, Arzu O. Synthesis of Novel Symmetrical 1,4-Disubstituted 1,2,3-Bistriazole Derivatives via ‘Click Chemistry’ and Their Biological Evaluation. Molecules, 21, 659 (2016).

Jyotirmaya S, Sudhir K. Medicinal interest of azo-based organic compounds. Asian J. Pharm. Clin. Res., 9(1): 33-39 (2016).

Sanjay F, Dinesh M, Manish P, Ranjan G, Synthesis and antibacterial activity of novel pyraazolo [3,4-b] quinoline base heterocyclic azo compounds and their dyeing performance, Saudi Pharm. J., 15(1): 48-54 (2007).

Garg H, Prakash C. Potential antidiabetics. Preparation of 4-arylazo-3,5-disubstituted-(2H)-1,2,6-thiadiazine 1,1-dioxides. J. Med. Chem., 15(4):435-436. (1972).

Thoraya A, Farghaly, Abdallah Z, Synthesis, azo-hydrazone tautomerism and antitumor screening of N-(3- ethoxycarbonyl-4,5,6,7-tetrahydro-benzo[b]thien-2-yl)-2- arylhydrazono-3-oxobutanamide derivatives. Arkivoc, 17, 295 (2008).

Sahoo J, Paidesetty S. Study of antimicrobial, analgesic, wound healing and antioxidant activities of some newly synthesized oxychinolin derivatives and their spectral characterization. J. Basic Appl. Sci., 4, 232-245 (2015).

Hosangadi, B, Dave R. an efficient general method for esterification of aromatic carboxylic acids. Tetrahedron Lett., 37, 6375-6378 (1996).

Fitton A, Smalley R. Practical heterocyclic chemistry. 1st ed., London; Academic Press Inc, 1968; 114-115.

Govindaraj S, Perumal P, Chinnasamy R, Synthesis and anti-microbial screening of novel schiff bases of 3-amino-2-methyl quinazolin-4-(3H)-one. J. Adv. Pharm. Technol. Res., 1(3): 320–325 (2010).

Redha I, Ahmed A, Yasmien K. Novel quinazolinone derivatives: synthesis and antimicrobial activity. Researcher, 2(4):82-88 (2010).

Vasantha M, Satyanarayana R, Synthesis and anti-diabetic activity of some 3- methylquinazolin-4(3H)-one derivatives. Int.J.Chem.Tech,Res.,6(14): 5647-5652 (2014).

Nazariy P, Olga S, Vasyl M. Synthesis of 1,2,3-triazole derivatives and evaluation of their anticancer activity. Sci.Pharm., 81(3): 663-676 ( 2013).

Nassar E, Abdelrazek F, Ayyad R, El-Farargy A. Synthesis and some reactions of 1-aryl-4-acetyl-5-methyl-1,2,3-triazole derivatives with anticonvulsant activity. Mini.Rev.Med.Chem., 16(11): 926-936 (2016).

Chandrasekaran, M, Venkatesalu V, Antibacterial and antifungal activity of syzygium jambolanum seeds. J. Ethnopharmacol., 91, 105-108 (2004).