SYNTHESIS AND ANTIMICROBIAL EVALUATION OF QUINAZOLINONE PEPTIDE DERIVATIVES

Bhupinder Kapoor; Arshid Nabi; Reena Gupta; Mukta Gupta

doi:10.22159/ajpcr.2017.v10s4.21329

Authors

Bhupinder Kapoor Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara â€“ 144 411, Punjab, India.
Arshid Nabi Department of Chemistry, University of Malaya, Kuala â€“ 50603, Lumpur, Malaysia.
Reena Gupta Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara â€“ 144 411, Punjab, India.
Mukta Gupta Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara â€“ 144 411, Punjab, India.

DOI:

https://doi.org/10.22159/ajpcr.2017.v10s4.21329

Keywords:

Quinazolinone, Peptide, Antimicrobial agents

Abstract

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Â Objective: The increased microbial resistance against commercially available drugs initiated the development of novel and safe antimicrobial agents in last few decades. In this view, a series of amino acid/dipeptide derivatives of quinazolin-3(4H)-one was synthesized and was evaluated for their antimicrobial potential.

Method: Synthesis of amino acid/peptide derivatives were carried out by coupling 5-(2-(2-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)-2-hydroxy benzoic acid with amino acid/dipeptide methyl esters in the presence of dicyclohexylcarbodiimide and N-methylmorpholine. The chemical structures of synthesized compounds were characterized by 1H nuclear magnetic resonance and infrared spectroscopy and were screened for antibacterial activity by disc diffusion method.

Results: All the synthesized derivatives exhibited moderate to significant antibacterial activity against both Gram-positive and Gram-negative bacteria. The potency of compound 5d was comparable to standard drug ciprofloxacin in all the strains of bacteria used. The compound 5a was found to be more active against Streptococcus pyogenes and Staphylococcus aureus while compound 5c against Pseudomonas aeruginosa and Escherichia coli.

Conclusion: Peptide derivatives of quinazolinone are promising antimicrobial agent and can be used for the synthesis of other novel compounds.

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Author Biography

Bhupinder Kapoor, Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara â€“ 144 411, Punjab, India.

School of Pharmaceutical Sciences, Asst. Prof

References

Akinyele TA, Igbinosa EO, Akinpelu DA, Okoh AI. In vitro assessment of the synergism between extracts of Cocos nucifera husk and some standard antibiotics. Asian Pac J Trop Biomed 2017;7(4):306-13.

Fernandes P, Martens E. Antibiotics in late clinical development. Biochem Pharmacol 2017;133(1):152-63.

Rather IA, Kim BC, Bajpai VK, Park YH. Self-medication and antibiotic resistance: Crisis, current challenges, and prevention. Saudi J Biol Sci 2017. DOI: 10.1016/j.sjbs.2017.01.004.

Dafale NA, Semwal UP, Rajput RK, Singh GN. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance. J Pharm Anal 2016;6:207-13.

Fajardo A, Linares JF, MartÃnez JL. Towards an ecological approach to antibiotics and antibiotic resistance genes. Clin Microbiol Infect 2009;15 Suppl 1:14-6.

Bengtsson-Palme J, Larsson DG. Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environ Int 2016;86:140-9.

Abbas SE, Barsoum FF, Georgey HH, Mohammed ER. Synthesis and antitumor activity of certain 2, 3, 6-trisubstituted quinazolin-4 (3H)-one derivatives. Bull Fac Pharm 2013;51:273-82.

Banu BH, Bharathi K, Prasad KV. Synthesis, characterization and evaluation of in vitro antioxidant and anti-inflammatory activity of 2-(4-oxo-2-phenylquinazolin-3 (4H)-yl) substituted acetic acids. IOSR J Pharm 2012;2:97-104.

Faraj FL, Zahedifard M, Paydar M, Looi CY, Majid NA, Ali HM, et al. Synthesis, characterization, and anticancer activity of new quinazoline derivatives against MCF-7 cells. Sci World J 2014;14:1-15.

Arora R, Kapoor A, Gill NS, Rana AC. Quinazolinone: An overview. Int Res J Pharm 2011;2(12):21-8.

Saad HA, Osman NA, Moustafa AH. Synthesis and analgesic activity of some new pyrazoles and triazoles bearing a 6, 8-dibromo-2- methylquinazoline moiety. Molecules 2011;16(12):10187-201.

Priya MG, Girija K, Ravichandran N. In vitro study of anti-inflammatory and antioxidant activity of 4-(3H)-quinazolinone derivatives. Rasayan J Chem 2011;4:418-24.

Rakesh KP, Manukumar HM, Gowda DC. Schiffâ€™s bases of quinazolinone derivatives: Synthesis and SAR studies of a novel series of potential anti-inflammatory and antioxidants. Bioorg Med Chem Lett 2015;25(5):1072-7.

Patel DR, Patel KC. Synthesis, characterization and in vitro antimicrobial screening of some new MCT reactive dyes bearing nitro quinazolinone moiety. J Saudi Chem Soc 2015;19(4):347-59.

Khodarahmi G, Jafari E, Hakimelahi G, Abedi D, Khajouei MR, Hassanzadeh F. Synthesis of some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iran J Pharm Res 2012;11:789-97.

Wang D, Gao F. Quinazoline derivatives: Synthesis and bioactivities. Chem Cent J 2013;7:1-15.

Kumar D, Mariappan G, Husain A, Monga J, Kumar S. Design, synthesis and cytotoxic evaluation of novel imidazolone fused quinazolinone derivatives. Arab J Chem 2017;10(3):344-50.

Keche AP, Kamble VM. Synthesis and anti-inflammatory and antimicrobial activities of some novel 2-methylquinazolin-4 (3H)-one derivatives bearing urea, thiourea and sulphonamide functionalities. Arab J Chem 2014. DOI: 10.1016/j.arabjc.2014.10.025.

Zayed MF, Hassan MH. Synthesis and biological evaluation studies of novel quinazolinone derivatives as antibacterial and anti-inflammatory agents. Saudi Pharm J 2014;22(2):157-62.

Devi K, Kachroo M. Synthesis and anti-tubercular activity of some new 2, 3-disubstituted quinazolinones. Pharm Chem 2014;6(5):353-9.

Refaie FM, Esmat AY, Gawad SM, Ibrahim AM, Mohamed MA. The anti-hyperlipidemic activities of 4 (3H) quinazolinone and two halogenated derivatives in rats. Lipids Health Dis 2005;4:1-11.

Gobinath M, Subramanian N, Alagarsamy V. Design, synthesis and H1-antihistaminic activity of novel 1-substituted-4-(3- chlorophenyl)-[1,2,4] triazo [4,3-a] quinazolin-5(4H)-ones. J Saudi Chem Soc 2015;19:282-6.

Gulick RM. New antiretroviral drugs. Clin Microbiol Infect 2003;9(3):186-93.

Laddha SS, Bhatnagar SP. Novel fused quinazolinones: Further studies on the anticonvulsant activity of 1,2,9,11-tetrasubstituted- 7H-thieno [2Ì,3Ì:4,5] pyrimido [6,1b]-quinazolin-7-one and 1,3,10,12-tetrasubstituted-8H-pyrido [2Ì,3Ì:4,5] pyrimido [6,1b] quinazolin-8-one. Future Med Chem 2010;2:565-73.

Kumar S, Kaur H, Kumar A. Synthesis of new azetidinonyl/ thiazolidinonyl quinazolinone derivatives as anti-parkinsonian agents. Arab J Chem 2012;5(4):475-84.

Chaudhary S, Singh RK, Gupta RK. Synthesis and biological activity of peptide derivatives of 2-hydroxy-5-(6-iodo-2-methyl- 4-oxoquinazolin-3 (4H)-yl) benzoic acid. Asian J Pharm Clin Res 2012;5:196-200.

Himaja M, Gupta N, Munirajeskhar D, Asif K, Sikarwar MS. Synthesis and biological evaluation of some N-methylated derivatives of thiazolylamino acids and peptides. J Pharm Sci Innov 2012;1:33-6.

GuzmÃ¡n F, Barberis S, Illanes A. Peptide synthesis: Chemical or enzymatic. Electron J Biotechnol 2007;10(2):279-314.

Pasupuleti M, Schmidtchen A, Malmsten M. Antimicrobial peptides: Key components of the innate immune system. Crit Rev Biotechnol 2012;32(2):143-71.

Ozaki KI, Yamada Y, Oine T, Ishizuka T, Iwasawa Y. Studies on 4 (1H)- quinazolinones. Synthesis and anti-inflammatory activity of 4 (1H)- quinazolinone derivatives. J Med Chem 1985;28(5):568-76.

Patel NB, Barat GG. In vitro microbial studies of new pyrazolyl quinazolin-4 (3H) ones. J Saudi Chem Soc 2010;14(2):157-64.

Balalaie S, Saeedi S, Ramezanpour S. Synthesis of pseudo-peptides containing a quinazolinone skeleton via Ugi four-component reaction. Helv Chim Acta 2016;99:138-42.

Dahiya R, Mourya R. Synthetic studies on novel nitroquinazolinone analogs with antimicrobial potential. Bull Pharm Res 2013;3(2):51-7.

Babu VV. Ultrasound accelerated synthesis of proteinogenic and Î±, Î±-dialkylamino acid ester salts. Indian J Chem 2006;45B:1942-4.

Kaur R, Kaur K, Gupta L, Dhir N, Gaganpreet. Synthesis and biological evaluation of gallic acid peptide derivatives. Int J Pharm Sci Rev Res 2014;28(1):16-21.

Dahiya R, Gautam H. Total synthesis and antimicrobial activity of a natural cycloheptapeptide of marine origin. Mar Drugs 2010;8(8):2384-94.

Sribalan R, Padmini V, Lavanya A, Ponnuvel K. Evaluation of antimicrobial activity of glycinate and carbonate derivatives of cholesterol: Synthesis and characterization. Saudi Pharm J 2016;24(6):658-68.

Routier S, SaugÃ© L, Ayerbe N, Coudert G, MÃ©rour JY. A mild and selective method for N-Boc deprotection. Tetrahedron Lett 2002;43:589-91.

Evans V, Mahon MF, Webster RL. A mild, copper-catalysed amide deprotection strategy: Use of tert-butyl as a protecting group. Tetrahedron 2014;70(41):7593-7.

Beale JM. Anti-infective agents. In: Block JH, Beale JM, Troy DB, editors. Wilson and Gisvoldâ€™s Textbook of Organic Medicinal and Pharmaceutical Chemistry. 11th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2015. p. 248-50.